Pub Date : 2024-06-04DOI: 10.1093/braincomms/fcae195
Sanyu Ge, Ling Zha, Yasuyoshi Kimura, Yoshimitsu Shimomura, Masayo Komatsu, Y. Gon, S. Komukai, Fumiko Murata, M. Maeda, K. Kiyohara, Tomotaka Sobue, T. Kitamura, Haruhisa Fukuda
The association between statin use and the risk of Parkinson’s disease remains inconclusive, particularly in Japan’s super-aging society. This study aimed to investigate the potential association between statin use and the risk of Parkinson’s disease among Japanese participants aged ≥65 years. We used data from the Longevity Improvement and Fair Evidence Study, which included medical and long-term care claims data from April 2014 to December 2020 across 17 municipalities. Using a nested case-control design, we matched one case to five controls based on age, sex, municipality, and cohort entry year. A conditional logistic regression model was used to estimate the odds ratios with 95% confidence intervals. Among the 56,186 participants (9,397 cases and 46, 789 controls), 53.6% were women. The inverse association between statin use and Parkinson’s disease risk was significant after adjusting for multiple variables (odds ratio: 0.61; 95% confidence interval: 0.56–0.66). Compared with non-users, the dose analysis revealed varying odds ratios: 1.30 (1.12–1.52) for 1–30 total standard daily doses, 0.77 (0.64–0.92) for 31-90 total standard daily doses, 0.62 (0.52–0.75) for 91–180 total standard daily doses, and 0.30 (0.25–0.35) for >180 total standard daily doses. Statin use among older Japanese adults was associated with a decreased risk of Parkinson’s disease. Notably, lower cumulative statin doses were associated with an elevated risk of Parkinson’s disease, whereas higher cumulative doses exhibited protective effects against Parkinson’s disease development.
{"title":"Statin use and risk of Parkinson’s disease among older adults in Japan: a nested case-control study using the longevity improvement and fair evidence study","authors":"Sanyu Ge, Ling Zha, Yasuyoshi Kimura, Yoshimitsu Shimomura, Masayo Komatsu, Y. Gon, S. Komukai, Fumiko Murata, M. Maeda, K. Kiyohara, Tomotaka Sobue, T. Kitamura, Haruhisa Fukuda","doi":"10.1093/braincomms/fcae195","DOIUrl":"https://doi.org/10.1093/braincomms/fcae195","url":null,"abstract":"\u0000 The association between statin use and the risk of Parkinson’s disease remains inconclusive, particularly in Japan’s super-aging society. This study aimed to investigate the potential association between statin use and the risk of Parkinson’s disease among Japanese participants aged ≥65 years. We used data from the Longevity Improvement and Fair Evidence Study, which included medical and long-term care claims data from April 2014 to December 2020 across 17 municipalities. Using a nested case-control design, we matched one case to five controls based on age, sex, municipality, and cohort entry year. A conditional logistic regression model was used to estimate the odds ratios with 95% confidence intervals. Among the 56,186 participants (9,397 cases and 46, 789 controls), 53.6% were women. The inverse association between statin use and Parkinson’s disease risk was significant after adjusting for multiple variables (odds ratio: 0.61; 95% confidence interval: 0.56–0.66). Compared with non-users, the dose analysis revealed varying odds ratios: 1.30 (1.12–1.52) for 1–30 total standard daily doses, 0.77 (0.64–0.92) for 31-90 total standard daily doses, 0.62 (0.52–0.75) for 91–180 total standard daily doses, and 0.30 (0.25–0.35) for >180 total standard daily doses. Statin use among older Japanese adults was associated with a decreased risk of Parkinson’s disease. Notably, lower cumulative statin doses were associated with an elevated risk of Parkinson’s disease, whereas higher cumulative doses exhibited protective effects against Parkinson’s disease development.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"5 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.1093/braincomms/fcae194
Ashley Ghaw, Alisha Chunduri, Arnold Chang, Richard Ortiz, Milena Kozlowska, P. Kulkarni, Craig F Ferris
LSD (lysergic acid diethylamide) is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of LSD in fully awake, drug naive rats. We hypothesized that LSD would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given intraperitoneal injections of vehicle or LSD in doses of 10 µg/kg or 100 µg/kg while fully awake during the imaging session. Changes in blood oxygen level dependent (BOLD) signal were recorded over a 30 min window. Approximately 45 min post injection data for resting state functional connectivity were collected All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific increases and decreases in global brain activity and changes in functional connectivity. Treatment with LSD resulted in a significant dose-dependent increase in negative BOLD signal. The areas most affected were the primary olfactory system, prefrontal cortex, thalamus and hippocampus. This was observed in both the number of voxels affected in these brains regions and the changes in BOLD signal over time. However, there was a significant increases in functional connectivity between the thalamus and somatosensory cortex, and the cerebellar nuclei and the surrounding brainstem areas. Contrary to our hypothesis, there was an acute dose-dependent increase in negative BOLD which can be interpreted as a decrease in brain activity, a finding that agrees with much of the behavioral data from preclinical studies. The enhanced connectivity between thalamus and sensory motor cortices is consistent with the human literature looking at LSD treatments in healthy human volunteers. The unexpected finding that LSD enhances connectivity to the cerebellar nuclei raises an interesting question concerning the role of this brain region in the psychotomimetic effects of hallucinogens.
{"title":"Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats","authors":"Ashley Ghaw, Alisha Chunduri, Arnold Chang, Richard Ortiz, Milena Kozlowska, P. Kulkarni, Craig F Ferris","doi":"10.1093/braincomms/fcae194","DOIUrl":"https://doi.org/10.1093/braincomms/fcae194","url":null,"abstract":"\u0000 LSD (lysergic acid diethylamide) is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of LSD in fully awake, drug naive rats. We hypothesized that LSD would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given intraperitoneal injections of vehicle or LSD in doses of 10 µg/kg or 100 µg/kg while fully awake during the imaging session. Changes in blood oxygen level dependent (BOLD) signal were recorded over a 30 min window. Approximately 45 min post injection data for resting state functional connectivity were collected All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific increases and decreases in global brain activity and changes in functional connectivity. Treatment with LSD resulted in a significant dose-dependent increase in negative BOLD signal. The areas most affected were the primary olfactory system, prefrontal cortex, thalamus and hippocampus. This was observed in both the number of voxels affected in these brains regions and the changes in BOLD signal over time. However, there was a significant increases in functional connectivity between the thalamus and somatosensory cortex, and the cerebellar nuclei and the surrounding brainstem areas. Contrary to our hypothesis, there was an acute dose-dependent increase in negative BOLD which can be interpreted as a decrease in brain activity, a finding that agrees with much of the behavioral data from preclinical studies. The enhanced connectivity between thalamus and sensory motor cortices is consistent with the human literature looking at LSD treatments in healthy human volunteers. The unexpected finding that LSD enhances connectivity to the cerebellar nuclei raises an interesting question concerning the role of this brain region in the psychotomimetic effects of hallucinogens.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"5 47","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1093/braincomms/fcae186
Pengde Guo, Jian Zhou, Yan Su, Weixin Wang, Haiqin Hua, Pengbo Zhao, Yan Wang, Shaohong Kang, Ming Liu
The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischemic optic neuropathy and 31 healthy controls, matched for age, sex, and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis. Compared with healthy controls, patients with non-arteritic anterior ischemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal, and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischemic optic neuropathy.
{"title":"Altered functional connectivity of the default mode network in non-arteritic anterior ischemic optic neuropathy","authors":"Pengde Guo, Jian Zhou, Yan Su, Weixin Wang, Haiqin Hua, Pengbo Zhao, Yan Wang, Shaohong Kang, Ming Liu","doi":"10.1093/braincomms/fcae186","DOIUrl":"https://doi.org/10.1093/braincomms/fcae186","url":null,"abstract":"\u0000 The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischemic optic neuropathy and 31 healthy controls, matched for age, sex, and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis.\u0000 Compared with healthy controls, patients with non-arteritic anterior ischemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal, and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischemic optic neuropathy.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"56 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141268875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1093/braincomms/fcae192
Nikita Neale, Frida Lona-Durazo, Mina Ryten, S. G. Gagliano Taliun
It is established that there are sex differences in terms of prevalence, age of onset, clinical manifestations, and response to treatment for a variety of brain disorders, including neurodevelopmental, psychiatric, and neurodegenerative disorders. Cohorts of increasing sample sizes with diverse data types collected, including genetic, transcriptomic and/or phenotypic data, are providing the building blocks to permit analytical designs to test for sex-biased genetic variant-trait associations, and for sex-biased transcriptional regulation. Such molecular assessments can contribute to our understanding of the manifested phenotypic differences between the sexes for brain disorders, offering the future possibility of delivering personalised therapy for females and males. With the intention of raising the profile of this field as a research priority, this review aims to shed light on the importance of investigating sex-genetic interactions for brain disorders, focusing on two areas: (i) variant-trait associations and (ii) transcriptomics (i.e., gene expression, transcript usage and regulation). We specifically discuss recent advances in the field, current gaps and provide considerations for future studies.
{"title":"Leveraging sex-genetic interactions to understand brain disorders: recent advances and current gaps","authors":"Nikita Neale, Frida Lona-Durazo, Mina Ryten, S. G. Gagliano Taliun","doi":"10.1093/braincomms/fcae192","DOIUrl":"https://doi.org/10.1093/braincomms/fcae192","url":null,"abstract":"\u0000 It is established that there are sex differences in terms of prevalence, age of onset, clinical manifestations, and response to treatment for a variety of brain disorders, including neurodevelopmental, psychiatric, and neurodegenerative disorders. Cohorts of increasing sample sizes with diverse data types collected, including genetic, transcriptomic and/or phenotypic data, are providing the building blocks to permit analytical designs to test for sex-biased genetic variant-trait associations, and for sex-biased transcriptional regulation. Such molecular assessments can contribute to our understanding of the manifested phenotypic differences between the sexes for brain disorders, offering the future possibility of delivering personalised therapy for females and males. With the intention of raising the profile of this field as a research priority, this review aims to shed light on the importance of investigating sex-genetic interactions for brain disorders, focusing on two areas: (i) variant-trait associations and (ii) transcriptomics (i.e., gene expression, transcript usage and regulation). We specifically discuss recent advances in the field, current gaps and provide considerations for future studies.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"41 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1093/braincomms/fcae182
Barbara Gisevius, Alexander Duscha, G. Poschmann, Kai Stühler, J. Motte, A. L. Fisse, Sanja Augustyniak, Adriana Rehm, P. Renk, Celina Böse, Diana Hubert, Kathrin Peters, Michelle Jagst, André Gömer, D. Todt, V. Bader, M. Tokic, Sarah Hirschberg, Christos Krogias, Nadine Trampe, Charlotta Coutourier, Carmen Winnesberg, E. Steinmann, K. Winklhofer, Ralf Gold, Aiden Haghikia
Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis (pwMS), supplementation of the short-chain fatty acid (SCFA) propionic acid (PA), as microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine, whether the neuroprotective impact of PA is a direct mode of action of SCFAs on CNS neurons. We analyzed neurite recovery in the presence of the SCFAs propionic acid (PA) and butyric acid (BA) in a reverse translational disease-in-a-dish model of human induced primary neurons (iPNs) differentiated from pwMS-derived induced pluripotent stem cells (iPSCs). We found that recovery of damaged neurites is induced by PA and BA, respectively. We could also show that administration of BA is able to enhance PA-associated neurite recovery. Whole cell proteome analysis of iPNs following recovery in the presence of PA revealed abundance changes of protein groups that are associated with the chromatin assembly, translational-, and metabolic processes. We further present evidence that these alterations in the chromatin assembly were associated with inhibition of histone deacetylases (HDAC) class I/II following both PA and BA treatment, mediated by free fatty acid receptor (FFAR) signaling. While neurite recovery in the presence of PA is promoted by activation of the anti-oxidative response, administration of BA increases neuronal ATP synthesis in pwMS-specific iPNs.
自身免疫性疾病多发性硬化症的神经变性仍然是一项重大的治疗挑战。针对炎症的有效药物只能部分缓解神经功能缺损的累积和疾病进展的转化。饮食和相关的肠道微生物组目前被认为是决定疾病发病和后续发展的关键环境风险因素。在多发性硬化症患者（pwMS）中，补充短链脂肪酸（SCFA）丙酸（PA）作为高纤维饮食发酵产生的微生物代谢产物，已被证明可以调节炎症，同时具有神经保护特性。我们试图确定 PA 的神经保护作用是否是 SCFAs 对中枢神经系统神经元的直接作用模式。我们分析了由 pwMS 衍生的诱导多能干细胞（iPSCs）分化而来的人类诱导原发性神经元（iPNs）的反向转化疾病模型中，在存在 SCFAs 丙酸（PA）和丁酸（BA）的情况下神经元的恢复情况。我们发现 PA 和 BA 可分别诱导受损神经元的恢复。我们还发现，给予 BA 能够增强 PA 相关神经元的恢复。在 PA 的存在下，iPNs 恢复后的全细胞蛋白质组分析揭示了与染色质组装、翻译和代谢过程相关的蛋白质组的丰度变化。我们还进一步提出证据表明，染色质组装的这些变化与 PA 和 BA 处理后组蛋白去乙酰化酶（HDAC）I/II 类的抑制有关，这种抑制是由游离脂肪酸受体（FFAR）信号传导介导的。在存在 PA 的情况下，神经元的恢复是通过激活抗氧化反应来促进的，而在 pwMS 特异性 iPNs 中，给予 BA 会增加神经元的 ATP 合成。
{"title":"Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons","authors":"Barbara Gisevius, Alexander Duscha, G. Poschmann, Kai Stühler, J. Motte, A. L. Fisse, Sanja Augustyniak, Adriana Rehm, P. Renk, Celina Böse, Diana Hubert, Kathrin Peters, Michelle Jagst, André Gömer, D. Todt, V. Bader, M. Tokic, Sarah Hirschberg, Christos Krogias, Nadine Trampe, Charlotta Coutourier, Carmen Winnesberg, E. Steinmann, K. Winklhofer, Ralf Gold, Aiden Haghikia","doi":"10.1093/braincomms/fcae182","DOIUrl":"https://doi.org/10.1093/braincomms/fcae182","url":null,"abstract":"\u0000 Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis (pwMS), supplementation of the short-chain fatty acid (SCFA) propionic acid (PA), as microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine, whether the neuroprotective impact of PA is a direct mode of action of SCFAs on CNS neurons. We analyzed neurite recovery in the presence of the SCFAs propionic acid (PA) and butyric acid (BA) in a reverse translational disease-in-a-dish model of human induced primary neurons (iPNs) differentiated from pwMS-derived induced pluripotent stem cells (iPSCs). We found that recovery of damaged neurites is induced by PA and BA, respectively. We could also show that administration of BA is able to enhance PA-associated neurite recovery. Whole cell proteome analysis of iPNs following recovery in the presence of PA revealed abundance changes of protein groups that are associated with the chromatin assembly, translational-, and metabolic processes. We further present evidence that these alterations in the chromatin assembly were associated with inhibition of histone deacetylases (HDAC) class I/II following both PA and BA treatment, mediated by free fatty acid receptor (FFAR) signaling. While neurite recovery in the presence of PA is promoted by activation of the anti-oxidative response, administration of BA increases neuronal ATP synthesis in pwMS-specific iPNs.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"29 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1093/braincomms/fcae184
Brenda Murage, Han Tan, Tomoji Mashimo, Mandy Jackson, Paul A Skehel
Amyotrophic Lateral Sclerosis is an age-dependent cell type-selective degenerative disease. Genetic studies indicate that Amyotrophic Lateral Sclerosis is part of a spectrum of disorders ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic Lateral Sclerosis type 8 is a familial disease caused by mis-sense mutations in VAPB. VAPB is localised to the cytoplasmic surface of the endoplasmic reticulum where it serves as a docking point for cytoplasmic proteins and mediates inter-organelle interactions with the endoplasmic reticulum membrane. A gene knock-in model of Amyotrophic Lateral Sclerosis type 8 based on the VapBP56S mutation and VapB gene deletion have been generated in the rat. These animals display a range of age-dependent phenotypes distinct from those previously reported in mouse models of Amyotrophic Lateral Sclerosis type 8. A loss of motor neurones in VapBP56S/+ and VapBP56S/P56Sanimals is indicated by a reduction in the number of large choline acetyl transferase-staining cells in the spinal cord. VapB-/-animals exhibit a relative increase in cytoplasmic TDP-43 levels compared to the nucleus, but no large protein aggregates. Concomitant with these spinal cord pathologies VapBP56S/+, VapBP56S/P56S and VapB-/-animals exhibit age-dependent changes in paw placement and exerted pressures when traversing a CatWalk apparatus, consistent with a somatosensory dysfunction. Extra motor dysfunction is reported in half the cases of motor neurone disease, and this is the first indication of an associated sensory dysfunction in a rodent model of Amyotrophic Lateral Sclerosis. Different rodent models may offer complementary experimental platforms with which to understand the human disease.
{"title":"Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis type 8","authors":"Brenda Murage, Han Tan, Tomoji Mashimo, Mandy Jackson, Paul A Skehel","doi":"10.1093/braincomms/fcae184","DOIUrl":"https://doi.org/10.1093/braincomms/fcae184","url":null,"abstract":"\u0000 Amyotrophic Lateral Sclerosis is an age-dependent cell type-selective degenerative disease. Genetic studies indicate that Amyotrophic Lateral Sclerosis is part of a spectrum of disorders ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic Lateral Sclerosis type 8 is a familial disease caused by mis-sense mutations in VAPB. VAPB is localised to the cytoplasmic surface of the endoplasmic reticulum where it serves as a docking point for cytoplasmic proteins and mediates inter-organelle interactions with the endoplasmic reticulum membrane. A gene knock-in model of Amyotrophic Lateral Sclerosis type 8 based on the VapBP56S mutation and VapB gene deletion have been generated in the rat. These animals display a range of age-dependent phenotypes distinct from those previously reported in mouse models of Amyotrophic Lateral Sclerosis type 8. A loss of motor neurones in VapBP56S/+ and VapBP56S/P56Sanimals is indicated by a reduction in the number of large choline acetyl transferase-staining cells in the spinal cord. VapB-/-animals exhibit a relative increase in cytoplasmic TDP-43 levels compared to the nucleus, but no large protein aggregates. Concomitant with these spinal cord pathologies VapBP56S/+, VapBP56S/P56S and VapB-/-animals exhibit age-dependent changes in paw placement and exerted pressures when traversing a CatWalk apparatus, consistent with a somatosensory dysfunction. Extra motor dysfunction is reported in half the cases of motor neurone disease, and this is the first indication of an associated sensory dysfunction in a rodent model of Amyotrophic Lateral Sclerosis. Different rodent models may offer complementary experimental platforms with which to understand the human disease.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"2 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1093/braincomms/fcae181
M. Boussac, Estelle Harroch, Christel Barthelemy, F. Ory-Magne, Clémence Leung, Margherita Fabbri, Christophe Arbus, Christine Brefel-Courbon
People with Parkinson’s disease with motor fluctuations can be treated by Continuous Subcutaneous Apomorphine Infusion (CSAI) to reduce their symptoms. Nonetheless, factors are lacking to predict patients’ quality-of-life amelioration after CSAI. This pilot study aimed to evaluate associations between personality dimensions and quality-of-life improvement after six months of CSAI. Thirty-nine people with Parkinson’s disease awaiting CSAI were included. Linear regression models between “Temperament and Character Inventory” personality dimensions at baseline and percentage of change in PDQ-39 (Parkinson’s Disease Questionnaire-39) scores after six months of CSAI were realized (n = 35). Temperament and Character Inventory was also compared between patients awaiting CSAI and patients awaiting deep brain stimulation of the sub-thalamic nucleus (n = 39 from the PREDI-STIM study). Higher Reward Dependence scores were associated with a better quality-of-life outcome after six months of CSAI, while Self-Directedness scores were associated with a better quality of life before CSAI (as opposed to Harm Avoidance, Reward Dependence, and Self-Transcendence scores associated with a worse quality of life). Moreover, people with Parkinson’s disease awaiting deep brain stimulation of the sub-thalamic nucleus had similar Temperament and Character Inventory dimensions compared to patients awaiting CSAI. People with Parkinson’s disease with higher Reward Dependence scores at baseline had the best quality-of-life improvement after six months of CSAI. This finding could be used to better prepare and accompany people with Parkinson’s disease during CSAI establishment. Moreover, this result could serve as an orientation factor to second-line treatments.
{"title":"Personality and quality-of-life improvement after apomorphine infusion in Parkinson’s disease","authors":"M. Boussac, Estelle Harroch, Christel Barthelemy, F. Ory-Magne, Clémence Leung, Margherita Fabbri, Christophe Arbus, Christine Brefel-Courbon","doi":"10.1093/braincomms/fcae181","DOIUrl":"https://doi.org/10.1093/braincomms/fcae181","url":null,"abstract":"\u0000 People with Parkinson’s disease with motor fluctuations can be treated by Continuous Subcutaneous Apomorphine Infusion (CSAI) to reduce their symptoms. Nonetheless, factors are lacking to predict patients’ quality-of-life amelioration after CSAI. This pilot study aimed to evaluate associations between personality dimensions and quality-of-life improvement after six months of CSAI.\u0000 Thirty-nine people with Parkinson’s disease awaiting CSAI were included. Linear regression models between “Temperament and Character Inventory” personality dimensions at baseline and percentage of change in PDQ-39 (Parkinson’s Disease Questionnaire-39) scores after six months of CSAI were realized (n = 35). Temperament and Character Inventory was also compared between patients awaiting CSAI and patients awaiting deep brain stimulation of the sub-thalamic nucleus (n = 39 from the PREDI-STIM study).\u0000 Higher Reward Dependence scores were associated with a better quality-of-life outcome after six months of CSAI, while Self-Directedness scores were associated with a better quality of life before CSAI (as opposed to Harm Avoidance, Reward Dependence, and Self-Transcendence scores associated with a worse quality of life). Moreover, people with Parkinson’s disease awaiting deep brain stimulation of the sub-thalamic nucleus had similar Temperament and Character Inventory dimensions compared to patients awaiting CSAI.\u0000 People with Parkinson’s disease with higher Reward Dependence scores at baseline had the best quality-of-life improvement after six months of CSAI. This finding could be used to better prepare and accompany people with Parkinson’s disease during CSAI establishment. Moreover, this result could serve as an orientation factor to second-line treatments.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"79 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141101442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1093/braincomms/fcae174
Pardis Zarifkar, M. Wagner, Patrick MacDonald Fisher, Dea Siggaard Stenbæk, Selina Kikkenborg Berg, Gitte Moos Knudsen, Michael E Benros, Daniel Kondziella, Christian Hassager
Survival rates after out-of-hospital cardiac arrest (OHCA) have improved over the past two decades. Despite this progress, long-term cognitive impairment remains prevalent even in those with early recovery of consciousness after OHCA; however, little is known about the determinants and underlying mechanisms. We utilized the REcovery after cardiac arrest surVIVAL (REVIVAL) cohort of OHCA survivors who fully regained consciousness to correlate cognition measurements with brain network changes using resting state functional MRI and the Montreal Cognitive Assessment (MoCA) at hospital discharge and a comprehensive neuropsychological assessment at three-month follow-up. About half of OHCA survivors displayed cognitive impairments at discharge, and in most, cognitive deficits persisted at three-month follow-up, particularly in the executive and visuospatial functions. Compared to healthy controls, OHCA survivors exhibited increased connectivity between resting-state networks, particularly involving the frontoparietal network. The increased connectivity between the frontoparietal and visual network was associated with less favorable cognitive outcomes (β=14.0, p=0.01), while higher education seemed to confer some cognitive protection (β=-2.06, p=0.03). In sum, the data highlight the importance of subtle cognitive impairment, also in OHCA survivors who are eligible for home discharge, and the potential of fMRI to identify alterations in brain networks correlating with cognitive outcomes.
{"title":"Brain network changes and cognitive function after cardiac arrest","authors":"Pardis Zarifkar, M. Wagner, Patrick MacDonald Fisher, Dea Siggaard Stenbæk, Selina Kikkenborg Berg, Gitte Moos Knudsen, Michael E Benros, Daniel Kondziella, Christian Hassager","doi":"10.1093/braincomms/fcae174","DOIUrl":"https://doi.org/10.1093/braincomms/fcae174","url":null,"abstract":"\u0000 Survival rates after out-of-hospital cardiac arrest (OHCA) have improved over the past two decades. Despite this progress, long-term cognitive impairment remains prevalent even in those with early recovery of consciousness after OHCA; however, little is known about the determinants and underlying mechanisms. We utilized the REcovery after cardiac arrest surVIVAL (REVIVAL) cohort of OHCA survivors who fully regained consciousness to correlate cognition measurements with brain network changes using resting state functional MRI and the Montreal Cognitive Assessment (MoCA) at hospital discharge and a comprehensive neuropsychological assessment at three-month follow-up. About half of OHCA survivors displayed cognitive impairments at discharge, and in most, cognitive deficits persisted at three-month follow-up, particularly in the executive and visuospatial functions. Compared to healthy controls, OHCA survivors exhibited increased connectivity between resting-state networks, particularly involving the frontoparietal network. The increased connectivity between the frontoparietal and visual network was associated with less favorable cognitive outcomes (β=14.0, p=0.01), while higher education seemed to confer some cognitive protection (β=-2.06, p=0.03). In sum, the data highlight the importance of subtle cognitive impairment, also in OHCA survivors who are eligible for home discharge, and the potential of fMRI to identify alterations in brain networks correlating with cognitive outcomes.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"13 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141106700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1093/braincomms/fcae162
Steffi De Meyer, Jolien M Schaeverbeke, Emma S Luckett, Mariska Reinartz, Elena R Blujdea, Isabelle Cleynen, Patrick Dupont, Koen Van Laere, Jeroen Vanbrabant, Erik Stoops, Eugeen Vanmechelen, Guglielmo di Molfetta, Henrik Zetterberg, Nicholas J Ashton, Charlotte E Teunissen, Koen Poesen, Rik Vandenberghe
The dynamic phase of preclinical Alzheimer’s disease, as characterised by accumulating cortical amyloid-β (Aβ), is a window of opportunity for Aβ lowering therapies to have greater efficacy. Biomarkers that accurately predict Aβ accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer’s disease therapies. We compared the ability of baseline plasma phosphorylated tau at threonine181 (pTau181), pTau217 and Aβ-PET load to predict future Aβ accumulation in asymptomatic elderly. In this longitudinal cohort study, baseline plasma pTau181 and pTau217 were quantified using single molecule array (Simoa) assays in cognitively unimpaired elderly selected from the community-recruited Flemish Prevent Alzheimer’s disease Cohort KU Leuven (F-PACK) based on the availability of baseline plasma samples and longitudinal Aβ-PET data (average time interval = 5 years, range 2 - 10 years). The predictive abilities of pTau181, pTau217 and PET-based Aβ measures for PET-based Aβ accumulation were investigated using receiver operating characteristic analyses, correlations and stepwise regression analyses. We included 75 F-PACK subjects (mean age = 70 years, 48% female), of which 16 were classified as Aβ accumulators (median [IQR] Centiloid rate of change = 3.42 [1.60] Centiloids/year). Plasma pTau181 (area under the curve (AUC) [95% CI] = 0.72 [0.59–0.86]) distinguished Aβ accumulators from non-accumulators with similar accuracy as pTau217 (AUC [95% CI] = 0.75 [0.62–0.88] and Aβ-PET (AUC [95% CI] = 0.72 [0.56–0.87]). Plasma pTau181 and pTau217 strongly correlated with each other (r = 0.93, PFDR < 0.001) and, together with Aβ-PET, similarly correlated with Aβ rate of change (rpTau181 = 0.33, rpTau217 = 0.36, rAβ-PET = 0.35, all PFDR ≤ 0.01). Addition of either plasma pTau181, plasma pTau217, or Aβ-PET to a linear demographic model including age, sex and APOE-ε4 carriership similarly improved the prediction of Aβ accumulation (ΔAkaike Information Criterion ≤ 4.1). In a multimodal biomarker model including all three biomarkers, each biomarker lost their individual predictive ability. These findings indicate that plasma pTau181, plasma pTau217 and Aβ-PET convey overlapping information and therefore predict the dynamic phase of asymptomatic amyloid-β accumulation with comparable performances. In clinical trial recruitment, confirmatory PET scans following blood-based prescreening might thus not provide additional value for detecting participants in these early disease stages who are destined to accumulate cortical Aβ. Given the moderate performances, future studies should investigate whether integrating plasma pTau species with other factors can improve performance and thus enhance clinical and research utility.
{"title":"Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid-PET","authors":"Steffi De Meyer, Jolien M Schaeverbeke, Emma S Luckett, Mariska Reinartz, Elena R Blujdea, Isabelle Cleynen, Patrick Dupont, Koen Van Laere, Jeroen Vanbrabant, Erik Stoops, Eugeen Vanmechelen, Guglielmo di Molfetta, Henrik Zetterberg, Nicholas J Ashton, Charlotte E Teunissen, Koen Poesen, Rik Vandenberghe","doi":"10.1093/braincomms/fcae162","DOIUrl":"https://doi.org/10.1093/braincomms/fcae162","url":null,"abstract":"\u0000 The dynamic phase of preclinical Alzheimer’s disease, as characterised by accumulating cortical amyloid-β (Aβ), is a window of opportunity for Aβ lowering therapies to have greater efficacy. Biomarkers that accurately predict Aβ accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer’s disease therapies. We compared the ability of baseline plasma phosphorylated tau at threonine181 (pTau181), pTau217 and Aβ-PET load to predict future Aβ accumulation in asymptomatic elderly.\u0000 In this longitudinal cohort study, baseline plasma pTau181 and pTau217 were quantified using single molecule array (Simoa) assays in cognitively unimpaired elderly selected from the community-recruited Flemish Prevent Alzheimer’s disease Cohort KU Leuven (F-PACK) based on the availability of baseline plasma samples and longitudinal Aβ-PET data (average time interval = 5 years, range 2 - 10 years). The predictive abilities of pTau181, pTau217 and PET-based Aβ measures for PET-based Aβ accumulation were investigated using receiver operating characteristic analyses, correlations and stepwise regression analyses.\u0000 We included 75 F-PACK subjects (mean age = 70 years, 48% female), of which 16 were classified as Aβ accumulators (median [IQR] Centiloid rate of change = 3.42 [1.60] Centiloids/year). Plasma pTau181 (area under the curve (AUC) [95% CI] = 0.72 [0.59–0.86]) distinguished Aβ accumulators from non-accumulators with similar accuracy as pTau217 (AUC [95% CI] = 0.75 [0.62–0.88] and Aβ-PET (AUC [95% CI] = 0.72 [0.56–0.87]). Plasma pTau181 and pTau217 strongly correlated with each other (r = 0.93, PFDR < 0.001) and, together with Aβ-PET, similarly correlated with Aβ rate of change (rpTau181 = 0.33, rpTau217 = 0.36, rAβ-PET = 0.35, all PFDR ≤ 0.01). Addition of either plasma pTau181, plasma pTau217, or Aβ-PET to a linear demographic model including age, sex and APOE-ε4 carriership similarly improved the prediction of Aβ accumulation (ΔAkaike Information Criterion ≤ 4.1). In a multimodal biomarker model including all three biomarkers, each biomarker lost their individual predictive ability.\u0000 These findings indicate that plasma pTau181, plasma pTau217 and Aβ-PET convey overlapping information and therefore predict the dynamic phase of asymptomatic amyloid-β accumulation with comparable performances. In clinical trial recruitment, confirmatory PET scans following blood-based prescreening might thus not provide additional value for detecting participants in these early disease stages who are destined to accumulate cortical Aβ. Given the moderate performances, future studies should investigate whether integrating plasma pTau species with other factors can improve performance and thus enhance clinical and research utility.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"28 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141106480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intracellular pH is a valuable index for predicting neuronal damage and injury. However, no PET probe is currently available for monitoring intracellular pH in vivo. In this study, we developed a new approach for visualizing the hydrolysis rate of monoacylglycerol lipase, which is widely distributed in neurons and astrocytes throughout the brain. This approach uses PET with the new radioprobe [11C]QST-0837 (1,1,1,3,3,3-hexafluoropropan-2-yl-3-(1-phenyl-1H-pyrazol-3-yl)azetidine-1-[11C]carboxylate), a covalent inhibitor containing an azetidine carbamate skeleton for monoacylglycerol lipase. The uptake and residence of this new radioprobe depends on the intracellular pH gradient, and we evaluated this with in silico, in vitro, and in vivo assessments. Molecular dynamics simulations predicted that because the azetidine carbamate moiety is close to that of water molecules, the compound containing azetidine carbamate would be more easily hydrolyzed following binding to monoacylglycerol lipase than would its analog containing a piperidine carbamate skeleton. Interestingly, it was difficult for monoacylglycerol lipase to hydrolyze the azetidine carbamate compound under weak-acidic (pH 6) conditions because of a change in the interactions with water molecules on the carbamate moiety of their complex. Subsequently, an in vitro assessment using rat brain homogenate to confirm the molecular dynamics simulation-predicted behavior of the azetidine carbamate compound showed that [11C]QST-0837 reacted with monoacylglycerol lipase to yield an [11C]complex, which was hydrolyzed to liberate 11CO2 as a final product. Additionally, the 11CO2 liberation rate was slower at lower pH. Finally, to indicate the feasibility of estimating how the hydrolysis rate depends on intracellular pH in vivo, we performed a PET study with [11C]QST-0837 using ischemic rats. In our proposed in vivo compartment model, the clearance rate of radioactivity from the brain reflected the rate of [11C]QST-0837 hydrolysis (clearance through the production of 11CO2) in the brain, which was lower in a remarkably hypoxic area than in the contralateral region. In conclusion, we indicated the potential for visualization of the intracellular pH gradient in the brain using PET imaging, although some limitations remain. This approach should permit further elucidation of the pathological mechanisms involved under acidic conditions in multiple CNS disorders.
细胞内 pH 值是预测神经元损伤的重要指标。然而，目前还没有 PET 探针可用于监测体内细胞内 pH 值。在这项研究中，我们开发了一种新方法来观察单酰基甘油脂肪酶的水解率，这种酶广泛分布于整个大脑的神经元和星形胶质细胞中。这种方法使用 PET 和新型放射性探针 [11C]QST-0837（1,1,1,3,3,3-六氟丙烷-2-基-3-(1-苯基-1H-吡唑-3-基)氮杂环丁烷-1-[11C]羧酸盐），这是一种含有氮杂环丁烷氨基甲酸酯骨架的单酰基甘油脂肪酶共价抑制剂。这种新型放射性探针的吸收和驻留取决于细胞内的 pH 梯度，我们通过硅学、体外和体内评估对此进行了评估。分子动力学模拟预测，由于氮杂环丁烷氨基甲酸酯分子接近于水分子的分子，与含有哌啶氨基甲酸酯骨架的类似物相比，含有氮杂环丁烷氨基甲酸酯的化合物在与单酰甘油脂肪酶结合后更容易水解。有趣的是，在弱酸性（pH 值为 6）条件下，单酰基甘油脂肪酶很难水解氮杂环丁烷氨基甲酸酯化合物，这是因为它们的复合物氨基甲酸酯分子与水分子的相互作用发生了变化。随后，为了证实分子动力学模拟预测的氮杂环丁烷氨基甲酸酯化合物的行为，使用大鼠脑匀浆进行了体外评估，结果显示[11C]QST-0837 与单酰基甘油脂肪酶反应生成了[11C]复合物，该复合物水解后的最终产物是 11CO2。此外，pH 值较低时，11CO2 的释放速度较慢。最后，为了说明在体内估计水解率如何取决于细胞内 pH 值的可行性，我们利用缺血大鼠进行了[11C]QST-0837 的 PET 研究。在我们提出的体内分区模型中，脑内放射性清除率反映了脑内[11C]QST-0837的水解率（通过产生11CO2清除），明显缺氧区域的水解率低于对侧区域。总之，我们指出了利用 PET 成像观察大脑细胞内 pH 梯度的潜力，尽管还存在一些局限性。这种方法应能进一步阐明多种中枢神经系统疾病在酸性条件下的病理机制。
{"title":"Potential for in vivo visualization of intracellular pH gradient in brain using PET imaging","authors":"Tomoteru Yamasaki, Wakana Mori, Takayuki Ohkubo, Atsuto Hiraishi, Yiding Zhang, Yusuke Kurihara, N. Nengaki, Hideaki Tashima, Masayuki Fujinaga, Ming-Rong Zhang","doi":"10.1093/braincomms/fcae172","DOIUrl":"https://doi.org/10.1093/braincomms/fcae172","url":null,"abstract":"\u0000 Intracellular pH is a valuable index for predicting neuronal damage and injury. However, no PET probe is currently available for monitoring intracellular pH in vivo. In this study, we developed a new approach for visualizing the hydrolysis rate of monoacylglycerol lipase, which is widely distributed in neurons and astrocytes throughout the brain. This approach uses PET with the new radioprobe [11C]QST-0837 (1,1,1,3,3,3-hexafluoropropan-2-yl-3-(1-phenyl-1H-pyrazol-3-yl)azetidine-1-[11C]carboxylate), a covalent inhibitor containing an azetidine carbamate skeleton for monoacylglycerol lipase. The uptake and residence of this new radioprobe depends on the intracellular pH gradient, and we evaluated this with in silico, in vitro, and in vivo assessments. Molecular dynamics simulations predicted that because the azetidine carbamate moiety is close to that of water molecules, the compound containing azetidine carbamate would be more easily hydrolyzed following binding to monoacylglycerol lipase than would its analog containing a piperidine carbamate skeleton. Interestingly, it was difficult for monoacylglycerol lipase to hydrolyze the azetidine carbamate compound under weak-acidic (pH 6) conditions because of a change in the interactions with water molecules on the carbamate moiety of their complex. Subsequently, an in vitro assessment using rat brain homogenate to confirm the molecular dynamics simulation-predicted behavior of the azetidine carbamate compound showed that [11C]QST-0837 reacted with monoacylglycerol lipase to yield an [11C]complex, which was hydrolyzed to liberate 11CO2 as a final product. Additionally, the 11CO2 liberation rate was slower at lower pH. Finally, to indicate the feasibility of estimating how the hydrolysis rate depends on intracellular pH in vivo, we performed a PET study with [11C]QST-0837 using ischemic rats. In our proposed in vivo compartment model, the clearance rate of radioactivity from the brain reflected the rate of [11C]QST-0837 hydrolysis (clearance through the production of 11CO2) in the brain, which was lower in a remarkably hypoxic area than in the contralateral region. In conclusion, we indicated the potential for visualization of the intracellular pH gradient in the brain using PET imaging, although some limitations remain. This approach should permit further elucidation of the pathological mechanisms involved under acidic conditions in multiple CNS disorders.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"44 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141111183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：