Sleep deprivation significantly affects both physiological and psychological health, with various experimental models used to study these impacts. This study compares three sleep deprivation models—Modified Multiple Platform Method (MMPM), treadmill method, and p-chlorophenylalanine (PCPA) method—on key physiological, cognitive, and emotional parameters in male Sprague-Dawley rats. The rats were subjected to 72 hours of sleep deprivation using these methods, followed by behavioral, cognitive, physiological, and biochemical assessments. Results indicated that the treadmill and PCPA methods led to significant reductions in both NREM and REM sleep (P < 0.05), with the PCPA method showing the most severe emotional effects, including heightened anxiety and depressive behaviors (P < 0.001). Cognitive impairments were most pronounced in the MMPM and treadmill groups (P < 0.01). All sleep deprivation models showed signs of autonomic nervous system dysfunction, as reflected by elevated LF/HF ratios in heart rate variability assessments (P < 0.05). Neurochemical analysis revealed reductions in hypothalamic 5-HT, Glu, and GABA levels, with the MMPM and treadmill methods causing more pronounced decreases (P < 0.05). Additionally, IL-2 levels significantly decreased while TNF-α levels increased in sleep-deprived rats compared to controls (P < 0.05). These findings highlight the distinct physiological, emotional, and cognitive impacts of different sleep deprivation models, providing a basis for model selection in future studies.
{"title":"Comparative analysis of sleep deprivation models: Impacts on sleep architecture, emotional state, cognitive function, and biochemical indicators in male rats","authors":"Yiyang Zhao , Runchen Fang , Hongsheng Bian , Kexing Zhang , Shuang Yu , Yanyan Wang , Lili Huang","doi":"10.1016/j.bbr.2025.115451","DOIUrl":"10.1016/j.bbr.2025.115451","url":null,"abstract":"<div><div>Sleep deprivation significantly affects both physiological and psychological health, with various experimental models used to study these impacts. This study compares three sleep deprivation models—Modified Multiple Platform Method (MMPM), treadmill method, and p-chlorophenylalanine (PCPA) method—on key physiological, cognitive, and emotional parameters in male Sprague-Dawley rats. The rats were subjected to 72 hours of sleep deprivation using these methods, followed by behavioral, cognitive, physiological, and biochemical assessments. Results indicated that the treadmill and PCPA methods led to significant reductions in both NREM and REM sleep (<em>P</em> < 0.05), with the PCPA method showing the most severe emotional effects, including heightened anxiety and depressive behaviors (<em>P</em> < 0.001). Cognitive impairments were most pronounced in the MMPM and treadmill groups (<em>P</em> < 0.01). All sleep deprivation models showed signs of autonomic nervous system dysfunction, as reflected by elevated LF/HF ratios in heart rate variability assessments (<em>P</em> < 0.05). Neurochemical analysis revealed reductions in hypothalamic 5-HT, Glu, and GABA levels, with the MMPM and treadmill methods causing more pronounced decreases (<em>P</em> < 0.05). Additionally, IL-2 levels significantly decreased while TNF-α levels increased in sleep-deprived rats compared to controls (<em>P</em> < 0.05). These findings highlight the distinct physiological, emotional, and cognitive impacts of different sleep deprivation models, providing a basis for model selection in future studies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115451"},"PeriodicalIF":2.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-28DOI: 10.1016/j.bbr.2025.115457
Jackson Tyler Boonstra
The cerebellum, once primarily associated with motor functions, has emerged as a critical component in higher cognitive processes and emotional regulation. This paradigm shift frames the cerebellum as an essential focal point for elucidating sophisticated functional brain circuitry. Network neuroscience often maintains a cortical-centric viewpoint, potentially overlooking the significant contributions of the cerebellum in connectome organization. Enhanced recognition and integration of cerebellar aspects in connectomic analyses hold significant potential for elucidating cerebellar circuitry within comprehensive brain networks and in neuropsychiatric conditions where cerebellar involvement is evident. This review explores the intricate anatomy, connectivity, and functional organization of the cerebellum within the broader context of large-scale brain networks. Cerebellar-specific networks are examined, emphasizing their role in supporting diverse cognitive functions via the cerebellum's hierarchical functional organization. The clinical significance of cerebellar connectomics is then addressed, highlighting the interplay between cerebellar circuitry and neurological and psychiatric conditions. The paper concludes by considering neurostimulation treatments and future directions in the field. This comprehensive review underscores the cerebellum's integral role in the human connectome.
{"title":"The cerebellar connectome","authors":"Jackson Tyler Boonstra","doi":"10.1016/j.bbr.2025.115457","DOIUrl":"10.1016/j.bbr.2025.115457","url":null,"abstract":"<div><div>The cerebellum, once primarily associated with motor functions, has emerged as a critical component in higher cognitive processes and emotional regulation. This paradigm shift frames the cerebellum as an essential focal point for elucidating sophisticated functional brain circuitry. Network neuroscience often maintains a cortical-centric viewpoint, potentially overlooking the significant contributions of the cerebellum in connectome organization. Enhanced recognition and integration of cerebellar aspects in connectomic analyses hold significant potential for elucidating cerebellar circuitry within comprehensive brain networks and in neuropsychiatric conditions where cerebellar involvement is evident. This review explores the intricate anatomy, connectivity, and functional organization of the cerebellum within the broader context of large-scale brain networks. Cerebellar-specific networks are examined, emphasizing their role in supporting diverse cognitive functions via the cerebellum's hierarchical functional organization. The clinical significance of cerebellar connectomics is then addressed, highlighting the interplay between cerebellar circuitry and neurological and psychiatric conditions. The paper concludes by considering neurostimulation treatments and future directions in the field. This comprehensive review underscores the cerebellum's integral role in the human connectome.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115457"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-27DOI: 10.1016/j.bbr.2025.115454
Guoqing Gao , Hailong Ge , Bei Rong , Limin Sun , Lujia Si , Junjie Huang , Chen Li , Junhua Huang , Lan Wu , Haomian Zhao , Mingzhe Zhou , Yinping Xie , Ling Xiao , Gaohua Wang
Background
The global burden of major depressive disorder (MDD) is rising, with current diagnostic methods hindered by significant subjectivity and low inter-rater reliability. Several studies have implied underlying link between coagulation-related proteins, such as kininogen (KNG) and coagulation factor VIII (FVIII), and depressive symptoms, offering new insights into the exploration of depression biomarkers. This study aims to elucidate the roles of KNG and FVIII in depression, potentially providing a foundational basis for biomarker research in this field.
Methods
A three-part experiment was conducted: (1) we measured serum levels of KNG and FVIII in the chronic unpredictable mild stress (CUMS) model; (2) KNG adeno-associated-virus overexpression (KNG-AAV-OE) model was constructed to further investigate the roles of KNG and FVIII. Meanwhile, quantity PCR, western blotting and immunofluorescence staining detected the KNG-FVIII pathway. (3) Peripheral blood samples were gathered from healthy control (HC, N = 21), as well as first-episode drug-naive patients with MDD (FEDN-MDD, N = 21), to further confirm the association between KNG, FVIII and depression.
Results
Firstly, serum KNG and FVIII levels were significantly elevated in the CUMS model. Then, the rats exhibited pronounced depressive-like behaviors in the KNG-AAV-OE model, with corresponding increases in serum KNG and FVIII. Lastly, clinical data showed increased KNG and FVIII levels in FEDN-MDD compared to HC. Furthermore, KNG and FVIII levels exhibited a strong positive correlation with the scores of the 24-item Hamilton Depression Scale and the 14-item Hamilton Anxiety Scale.
Conclusion
To sum up, this study highlights critical roles of serum KNG and FVIII in depression and the KNG-AAV-OE may lead the augment of FVIII in serum. Consequently, our research may offer new evidence and foundation for depression biomarkers research in the future.
{"title":"Serum KNG and FVIII may serve as potential biomarkers for depression","authors":"Guoqing Gao , Hailong Ge , Bei Rong , Limin Sun , Lujia Si , Junjie Huang , Chen Li , Junhua Huang , Lan Wu , Haomian Zhao , Mingzhe Zhou , Yinping Xie , Ling Xiao , Gaohua Wang","doi":"10.1016/j.bbr.2025.115454","DOIUrl":"10.1016/j.bbr.2025.115454","url":null,"abstract":"<div><h3>Background</h3><div>The global burden of major depressive disorder (MDD) is rising, with current diagnostic methods hindered by significant subjectivity and low inter-rater reliability. Several studies have implied underlying link between coagulation-related proteins, such as kininogen (KNG) and coagulation factor VIII (FVIII), and depressive symptoms, offering new insights into the exploration of depression biomarkers. This study aims to elucidate the roles of KNG and FVIII in depression, potentially providing a foundational basis for biomarker research in this field.</div></div><div><h3>Methods</h3><div>A three-part experiment was conducted: (1) we measured serum levels of KNG and FVIII in the chronic unpredictable mild stress (CUMS) model; (2) KNG adeno-associated-virus overexpression (KNG-AAV-OE) model was constructed to further investigate the roles of KNG and FVIII. Meanwhile, quantity PCR, western blotting and immunofluorescence staining detected the KNG-FVIII pathway. (3) Peripheral blood samples were gathered from healthy control (HC, N = 21), as well as first-episode drug-naive patients with MDD (FEDN-MDD, N = 21), to further confirm the association between KNG, FVIII and depression.</div></div><div><h3>Results</h3><div>Firstly, serum KNG and FVIII levels were significantly elevated in the CUMS model. Then, the rats exhibited pronounced depressive-like behaviors in the KNG-AAV-OE model, with corresponding increases in serum KNG and FVIII. Lastly, clinical data showed increased KNG and FVIII levels in FEDN-MDD compared to HC. Furthermore, KNG and FVIII levels exhibited a strong positive correlation with the scores of the 24-item Hamilton Depression Scale and the 14-item Hamilton Anxiety Scale.</div></div><div><h3>Conclusion</h3><div>To sum up, this study highlights critical roles of serum KNG and FVIII in depression and the KNG-AAV-OE may lead the augment of FVIII in serum. Consequently, our research may offer new evidence and foundation for depression biomarkers research in the future.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115454"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tactile information from the whiskers (vibrissae) travels through the somatosensory cortex to the entorhinal cortex and the hippocampus, influencing development and psychological well-being. The lack of whiskers affects cognitive functions, spatial memory, neuronal firing, spatial mapping, and neurogenesis in the dorsal hippocampus. Recent studies underline the importance of tactile experiences in emotional health, noting that while tactile stimuli modulate the dorsal hippocampus, the effects of tactile deprivation on anxiety-like behaviors and neural activity in regions like the ventral hippocampus and amygdala are less understood. This study aims to investigate the impact of permanent tactile deprivation on modifying anxiety-like behaviors and c-Fos expression (a marker of neuronal activity) in the dorsolateral and central nucleus of the amygdala and the ventral hippocampus, two regions involved in emotional memory and anxiety. We sectioned the infraorbital nerve, responsible for transmitting whisker information, in CD1 mice to examine how tactile deprivation modifies the behavioral activity in the Elevated Plus Maze and Open-Field Test. Our data revealed a reduction in anxiety-related behaviors post-deprivation, which was linked to a significant decrease in c-Fos expression in the barrel cortex, as well as ventral hippocampus (CA1, dentate gyrus) and dorsolateral, central nucleus of the amygdala, suggesting impaired processing in emotional-regulator brain regions. In conclusion, tactile inputs reduce neuronal activity regulators in brain regions related to emotional regulation, which may trigger possible failures in risk perception or self-protective behaviors associated with the lack of appropriate anxiety responses.
{"title":"Permanent tactile sensory loss reduces neuronal activity in the amygdala and ventral hippocampus and alters anxiety-like behaviors","authors":"Nereida Ibarra-Castaneda , Veronica Lopez-Virgen , Norma Moy-Lopez , Oscar Gonzalez-Perez","doi":"10.1016/j.bbr.2025.115456","DOIUrl":"10.1016/j.bbr.2025.115456","url":null,"abstract":"<div><div>Tactile information from the whiskers (vibrissae) travels through the somatosensory cortex to the entorhinal cortex and the hippocampus, influencing development and psychological well-being. The lack of whiskers affects cognitive functions, spatial memory, neuronal firing, spatial mapping, and neurogenesis in the dorsal hippocampus. Recent studies underline the importance of tactile experiences in emotional health, noting that while tactile stimuli modulate the dorsal hippocampus, the effects of tactile deprivation on anxiety-like behaviors and neural activity in regions like the ventral hippocampus and amygdala are less understood. This study aims to investigate the impact of permanent tactile deprivation on modifying anxiety-like behaviors and c-Fos expression (a marker of neuronal activity) in the dorsolateral and central nucleus of the amygdala and the ventral hippocampus, two regions involved in emotional memory and anxiety. We sectioned the infraorbital nerve, responsible for transmitting whisker information, in CD1 mice to examine how tactile deprivation modifies the behavioral activity in the Elevated Plus Maze and Open-Field Test. Our data revealed a reduction in anxiety-related behaviors post-deprivation, which was linked to a significant decrease in c-Fos expression in the barrel cortex, as well as ventral hippocampus (CA1, dentate gyrus) and dorsolateral, central nucleus of the amygdala, suggesting impaired processing in emotional-regulator brain regions. In conclusion, tactile inputs reduce neuronal activity regulators in brain regions related to emotional regulation, which may trigger possible failures in risk perception or self-protective behaviors associated with the lack of appropriate anxiety responses.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115456"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-26DOI: 10.1016/j.bbr.2025.115452
Nicolas Cabe , Shailendra Segobin , Céline Boudehent , Alice Laniepce , Anne Lise Pitel
Background
While Alcohol Use Disorder (AUD) is frequently associated with impulsivity, its structural brain substrates are still poorly defined. The triadic model of addiction postulates that impulsive behavior is regulated by an amygdalo-striatal impulsive subcomponent, a prefrontal and cerebellar reflective subcomponent, and an insular regulatory subcomponent. The objective of this study was thus to examine the relationships between self-evaluated impulsivity and structural brain abnormalities in patients with severe AUD (sAUD) using the triadic model as a theoretical framework.
Methods
Twenty-two inpatients with sAUD and 17 Healthy Controls (HC) completed two impulsivity scales: the Barratt Impulsiveness Scale-11 (BIS-11), and the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsive Behavior Scale (UPPS). They also underwent an anatomical MRI. The brain volumes of the regions described as involved in the three subcomponents of the triadic model were extracted.
Results
The two groups did not significantly differ on self-reported impulsivity measures. However, the volumes of the caudate nuclei, executive cerebellum and insula were smaller in sAUD than in HC. In the sAUD group there were significant positive correlations between certain impulsivity measures and gray matter volume of the nucleus accumbens.
Conclusions
In sAUD, self-evaluated impulsivity specifically relates to the integrity of the ventral striatum that belongs to the impulsive subcomponent of the triadic neurocognitive model of addiction. It is not related to the integrity or deterioration of the brain regions that underlie the reflexive or regulatory sub-component. Although these results have methodological limitations, they are consistent with the impulsive/compulsive model of addiction and confirms the persistence of the relationship between impulsivity and ventral striatum in sAUD.
{"title":"Exploratory structural neuroimaging examination of impulsivity in severe alcohol use disorder: Persistent implication of the ventral striatum","authors":"Nicolas Cabe , Shailendra Segobin , Céline Boudehent , Alice Laniepce , Anne Lise Pitel","doi":"10.1016/j.bbr.2025.115452","DOIUrl":"10.1016/j.bbr.2025.115452","url":null,"abstract":"<div><h3>Background</h3><div>While Alcohol Use Disorder (AUD) is frequently associated with impulsivity, its structural brain substrates are still poorly defined. The triadic model of addiction postulates that impulsive behavior is regulated by an amygdalo-striatal impulsive subcomponent, a prefrontal and cerebellar reflective subcomponent, and an insular regulatory subcomponent. The objective of this study was thus to examine the relationships between self-evaluated impulsivity and structural brain abnormalities in patients with severe AUD (sAUD) using the triadic model as a theoretical framework.</div></div><div><h3>Methods</h3><div>Twenty-two inpatients with sAUD and 17 Healthy Controls (HC) completed two impulsivity scales: the Barratt Impulsiveness Scale-11 (BIS-11), and the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsive Behavior Scale (UPPS). They also underwent an anatomical MRI. The brain volumes of the regions described as involved in the three subcomponents of the triadic model were extracted.</div></div><div><h3>Results</h3><div>The two groups did not significantly differ on self-reported impulsivity measures. However, the volumes of the caudate nuclei, executive cerebellum and insula were smaller in sAUD than in HC. In the sAUD group there were significant positive correlations between certain impulsivity measures and gray matter volume of the nucleus accumbens.</div></div><div><h3>Conclusions</h3><div>In sAUD, self-evaluated impulsivity specifically relates to the integrity of the ventral striatum that belongs to the impulsive subcomponent of the triadic neurocognitive model of addiction. It is not related to the integrity or deterioration of the brain regions that underlie the reflexive or regulatory sub-component. Although these results have methodological limitations, they are consistent with the impulsive/compulsive model of addiction and confirms the persistence of the relationship between impulsivity and ventral striatum in sAUD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"483 ","pages":"Article 115452"},"PeriodicalIF":2.6,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-25DOI: 10.1016/j.bbr.2025.115442
Yu-Ying Zhao , Zi-Jun Wu , Yue Du , Qing-qing Han , Yuan-yuan Bai , Bin Liu , Jing Li
Neuropathic pain (NP) is a chronic disease state centred on neuroinflammation with a high prevalence and limited effective treatment options. Peroxisome proliferator-activated receptor α (PPARα) has emerged as a promising target for NP management due to its anti-inflammatory properties. Recent evidence highlights the critical role of the gut microbiome and its metabolites in NP pathogenesis. This study aimed to investigate whether PPARα modulates the development and alleviation of NP by influencing gut microbial communities and serum metabolites. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS/MS) untargeted metabolomics analyses performed 14 days after the establishment of a chronic constriction injury (CCI) pain model in C57BL/6 J mice showed significant changes in gut microbial and metabolite levels in CCI mice. Intraperitoneal injection of the PPARα agonist GW7647 (5 mg/kg) significantly attenuated mechanical allodynia and thermal hyperalgesia in CCI mice, whereas injection of the PPARα antagonist GW6471 (20 mg/kg) produced the opposite effect. Immunofluorescence analysis revealed that GW7647 effectively suppressed microglial activation. Additionally, PPARα agonist and antagonist treatments markedly altered the composition and abundance of intestinal microbial communities in CCI mice. Further serum LC-MS/MS analysis identified 258 potential serum metabolic biomarkers, many of which correlated with changes in gut microbial composition. These findings demonstrate that PPARα influences serum metabolite profiles by modulating gut microbiota composition, which subsequently affects NP progression. This study provides novel insights into the mechanisms underlying NP and suggests potential therapeutic avenues targeting PPARα and gut microbiota.
{"title":"Gut microbiome and serum metabolites in neuropathic pain: The PPARα perspective","authors":"Yu-Ying Zhao , Zi-Jun Wu , Yue Du , Qing-qing Han , Yuan-yuan Bai , Bin Liu , Jing Li","doi":"10.1016/j.bbr.2025.115442","DOIUrl":"10.1016/j.bbr.2025.115442","url":null,"abstract":"<div><div>Neuropathic pain (NP) is a chronic disease state centred on neuroinflammation with a high prevalence and limited effective treatment options. Peroxisome proliferator-activated receptor α (PPARα) has emerged as a promising target for NP management due to its anti-inflammatory properties. Recent evidence highlights the critical role of the gut microbiome and its metabolites in NP pathogenesis. This study aimed to investigate whether PPARα modulates the development and alleviation of NP by influencing gut microbial communities and serum metabolites. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS/MS) untargeted metabolomics analyses performed 14 days after the establishment of a chronic constriction injury (CCI) pain model in C57BL/6 J mice showed significant changes in gut microbial and metabolite levels in CCI mice. Intraperitoneal injection of the PPARα agonist GW7647 (5 mg/kg) significantly attenuated mechanical allodynia and thermal hyperalgesia in CCI mice, whereas injection of the PPARα antagonist GW6471 (20 mg/kg) produced the opposite effect. Immunofluorescence analysis revealed that GW7647 effectively suppressed microglial activation. Additionally, PPARα agonist and antagonist treatments markedly altered the composition and abundance of intestinal microbial communities in CCI mice. Further serum LC-MS/MS analysis identified 258 potential serum metabolic biomarkers, many of which correlated with changes in gut microbial composition. These findings demonstrate that PPARα influences serum metabolite profiles by modulating gut microbiota composition, which subsequently affects NP progression. This study provides novel insights into the mechanisms underlying NP and suggests potential therapeutic avenues targeting PPARα and gut microbiota.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115442"},"PeriodicalIF":2.6,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.bbr.2025.115440
Ghallab Alotaibi, Amna Khan, Shafiqur Rahman
The astroglial glutamate transporter in the hippocampus and anterior cingulate cortex (ACC) is critically involved in chronic pain-induced cognitive and psychiatric abnormalities. We have previously reported that LDN-212320, a glutamate transporter-1 (GLT-1) activator, attenuates complete Freund’s adjuvant (CFA)-induced acute and chronic nociceptive pain. However, the cellular and molecular mechanisms underlying GLT-1 modulation in the hippocampus and ACC during chronic pain-induced cognitive deficit-like and anxiety-like behaviors remain unknown. Here, we have investigated the effects of LDN-212320 on CFA-induced chronic pain associated with cognitive deficit-like and anxiety-like behaviors in mice. We have evaluated the effects of LDN-212320 on CFA-induced impaired spatial, working, and recognition memory using Y-maze and object-place recognition tests. In addition, we have determined the effects of LDN-21230 on chronic pain-induced anxiety-like behaviors using elevated plus maze and marble burying test. We have also examined the effects of LDN-212320 on cAMP response element-binding protein (pCREB), brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), and Ca2 +/calmodulin-dependent protein kinase II (CaMKII) expression in the hippocampus and ACC during CFA-induced cognitive deficit-like and anxiety-like behaviors using the Western blot analysis and immunofluorescence assay. Pretreatment with LDN-212320 (20 mg/kg) significantly attenuated CFA-induced impaired spatial, working, and recognition memory. Furthermore, LDN-212320 (20 mg/kg) significantly reduced CFA-induced anxiety-like behaviors. Additionally, LDN-212320 (20 mg/kg) significantly reversed CFA-induced decreased pCREB, BDNF, PKA and CaMKII expression in the hippocampus and ACC. Overall, these results suggest that the LDN-212320 prevents CFA-induced cognitive deficit-like and anxiety-like behaviors by activating CaMKII/CREB/BDNF signaling pathway in the hippocampus and ACC. Therefore, LDN-212320 could be a potential treatment for chronic pain associated with cognitive impairment and anxiety-like behaviors.
{"title":"Glutamate transporter activator LDN-212320 prevents chronic pain-induced cognitive impairment and anxiety-like behaviors in a mouse model","authors":"Ghallab Alotaibi, Amna Khan, Shafiqur Rahman","doi":"10.1016/j.bbr.2025.115440","DOIUrl":"10.1016/j.bbr.2025.115440","url":null,"abstract":"<div><div>The astroglial glutamate transporter in the hippocampus and anterior cingulate cortex (ACC) is critically involved in chronic pain-induced cognitive and psychiatric abnormalities. We have previously reported that LDN-212320, a glutamate transporter-1 (GLT-1) activator, attenuates complete Freund’s adjuvant (CFA)-induced acute and chronic nociceptive pain. However, the cellular and molecular mechanisms underlying GLT-1 modulation in the hippocampus and ACC during chronic pain-induced cognitive deficit-like and anxiety-like behaviors remain unknown. Here, we have investigated the effects of LDN-212320 on CFA-induced chronic pain associated with cognitive deficit-like and anxiety-like behaviors in mice. We have evaluated the effects of LDN-212320 on CFA-induced impaired spatial, working, and recognition memory using Y-maze and object-place recognition tests. In addition, we have determined the effects of LDN-21230 on chronic pain-induced anxiety-like behaviors using elevated plus maze and marble burying test. We have also examined the effects of LDN-212320 on cAMP response element-binding protein (pCREB), brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), and Ca<sup>2 +</sup>/calmodulin-dependent protein kinase II (CaMKII) expression in the hippocampus and ACC during CFA-induced cognitive deficit-like and anxiety-like behaviors using the Western blot analysis and immunofluorescence assay. Pretreatment with LDN-212320 (20 mg/kg) significantly attenuated CFA-induced impaired spatial, working, and recognition memory. Furthermore, LDN-212320 (20 mg/kg) significantly reduced CFA-induced anxiety-like behaviors. Additionally, LDN-212320 (20 mg/kg) significantly reversed CFA-induced decreased pCREB, BDNF, PKA and CaMKII expression in the hippocampus and ACC. Overall, these results suggest that the LDN-212320 prevents CFA-induced cognitive deficit-like and anxiety-like behaviors by activating CaMKII/CREB/BDNF signaling pathway in the hippocampus and ACC. Therefore, LDN-212320 could be a potential treatment for chronic pain associated with cognitive impairment and anxiety-like behaviors.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115440"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.bbr.2025.115437
Niels Hansen , Bianca Teegen , Sina Hirschel , Janosch Fox , Dirk Fitzner , Jens Wiltfang , Claudia Bartels
Background
Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD.
Methods
We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen. Neuropsychological test results and autoantibody testing in serum over a period of 4–5 years is provided.
Report
Our patient exhibited mild dementia syndrome and was diagnosed with AD on the basis of a prototypical biomarker profile (reduced Aβ42/40 ratio and elevated p-tau181 protein in cerebrospinal fluid). Within a 5-year follow-up with regular visits to our memory clinic, we observed a nearly stable neuropsychological profile of mild, amnestic variant dementia that did not noticeably progress. KCNA2 autoantibodies were also detectable in serum over 4 years with increasing titers over time. Combined anti-dementia therapy with donepezil, multimodal therapy including non-pharmacological cognitive therapy, and immunotherapy with intravenous methylprednisolone was carried out as an individual treatment approach.
Conclusions
KCNA2 autoantibody persistence in biomarker-supported AD does not necessarily trigger a poor outcome in the long-term, as cognitive impairment did not progress subsequently. At the same time, mild immunotherapy did not result in less immunoreactivity in conjunction with the detection of KCNA2 autoantibodies. This detection of KCNA2 autoantibodies in AD could provide indices of a potentially benign long-term AD course that should be further evaluated in studies.
{"title":"Longitudinally persisting KCNA2-autoantibodies in mild amnestic dementia with Alzheimer´s pathology – Report and literature review","authors":"Niels Hansen , Bianca Teegen , Sina Hirschel , Janosch Fox , Dirk Fitzner , Jens Wiltfang , Claudia Bartels","doi":"10.1016/j.bbr.2025.115437","DOIUrl":"10.1016/j.bbr.2025.115437","url":null,"abstract":"<div><h3>Background</h3><div>Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD.</div></div><div><h3>Methods</h3><div>We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen. Neuropsychological test results and autoantibody testing in serum over a period of 4–5 years is provided.</div></div><div><h3>Report</h3><div>Our patient exhibited mild dementia syndrome and was diagnosed with AD on the basis of a prototypical biomarker profile (reduced Aβ42/40 ratio and elevated p-tau181 protein in cerebrospinal fluid). Within a 5-year follow-up with regular visits to our memory clinic, we observed a nearly stable neuropsychological profile of mild, amnestic variant dementia that did not noticeably progress. KCNA2 autoantibodies were also detectable in serum over 4 years with increasing titers over time. Combined anti-dementia therapy with donepezil, multimodal therapy including non-pharmacological cognitive therapy, and immunotherapy with intravenous methylprednisolone was carried out as an individual treatment approach.</div></div><div><h3>Conclusions</h3><div>KCNA2 autoantibody persistence in biomarker-supported AD does not necessarily trigger a poor outcome in the long-term, as cognitive impairment did not progress subsequently. At the same time, mild immunotherapy did not result in less immunoreactivity in conjunction with the detection of KCNA2 autoantibodies. This detection of KCNA2 autoantibodies in AD could provide indices of a potentially benign long-term AD course that should be further evaluated in studies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115437"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.bbr.2025.115443
Jiahua Zhang , Dongpeng Wu , Hongping Wang , Yue Yu , Yue Zhao , Hao Zheng , Shaoyang Wang , Siyu Fan , Xiaonan Pang , Kai Wang , Yanghua Tian
Non-suicidal self-injury (NSSI) is prevalent among adolescent populations worldwide, yet its neuropathological mechanisms remain unclear. This study aimed to investigate brain functional differences in NSSI patients by utilizing large-scale functional networks and examining their correlation with clinical outcomes. Cross-sectional clinical and functional magnetic resonance imaging (fMRI) data were collected from 42 patients and 47 healthy controls. Independent component analysis (ICA) was utilized to investigate changes in both intra-network and inter-network functional connectivity. We then investigated the potential association between functional network connectivity and clinical self-injurious behavior. The results revealed significant abnormalities in intra-network functional connectivity within the left middle cingulum gyrus, right angular gyrus, and middle frontal gyrus in patients with NSSI. Additionally, we found altered inter-network connectivity patterns, particularly between higher-order cognitive networks and primary sensory networks, suggesting potential disruptions in multisensory integration and emotional regulation in these patients. This study revealed significant alterations in large-scale functional network connectivity in adolescents with depression and NSSI, particularly in networks related to emotion regulation and cognitive control. These findings provide novel perspectives on the neurobiological mechanisms of NSSI and suggest possible avenues for early intervention and treatment.
{"title":"Large-scale functional network connectivity alterations in adolescents with major depression and non-suicidal self-injury","authors":"Jiahua Zhang , Dongpeng Wu , Hongping Wang , Yue Yu , Yue Zhao , Hao Zheng , Shaoyang Wang , Siyu Fan , Xiaonan Pang , Kai Wang , Yanghua Tian","doi":"10.1016/j.bbr.2025.115443","DOIUrl":"10.1016/j.bbr.2025.115443","url":null,"abstract":"<div><div>Non-suicidal self-injury (NSSI) is prevalent among adolescent populations worldwide, yet its neuropathological mechanisms remain unclear. This study aimed to investigate brain functional differences in NSSI patients by utilizing large-scale functional networks and examining their correlation with clinical outcomes. Cross-sectional clinical and functional magnetic resonance imaging (fMRI) data were collected from 42 patients and 47 healthy controls. Independent component analysis (ICA) was utilized to investigate changes in both intra-network and inter-network functional connectivity. We then investigated the potential association between functional network connectivity and clinical self-injurious behavior. The results revealed significant abnormalities in intra-network functional connectivity within the left middle cingulum gyrus, right angular gyrus, and middle frontal gyrus in patients with NSSI. Additionally, we found altered inter-network connectivity patterns, particularly between higher-order cognitive networks and primary sensory networks, suggesting potential disruptions in multisensory integration and emotional regulation in these patients. This study revealed significant alterations in large-scale functional network connectivity in adolescents with depression and NSSI, particularly in networks related to emotion regulation and cognitive control. These findings provide novel perspectives on the neurobiological mechanisms of NSSI and suggest possible avenues for early intervention and treatment.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115443"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1016/j.bbr.2025.115441
Teresa Belem Mares-Barbosa , Ares Orlando Cuellar-Santoyo , Victor Manuel Ruiz-Rodríguez , Karen Hernández-Balderas , Osiel González-Hernández , Diana Patricia Portales-Pérez , Ana María Estrada-Sánchez
Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7). In the present study, we evaluated the effect of intraperitoneal administration of subanesthetic ketamine dose (30 mg/Kg) for fourteen days on young (35 days of age) and adult (76 days of age) mice on different behavioral tests. Nest-building behavior was evaluated during the fourteen-day treatment; short-term memory and social interaction tests were assessed twenty-four hours after the last administration of ketamine. Interestingly, only adult mice treated with ketamine showed impaired nest-building and novel object recognition. In the hippocampus, an area related to memory and cognition, ketamine administration showed no changes in the relative expression of GluN1, P2X4, and P2X7 while increasing GluA2 and P2X1 only in young mice. In contrast, when assessing the protein levels of P2X1 and P2X7 in the hippocampus following ketamine treatment, young mice exhibited a decrease in P2X1 levels while P2X7 levels increased. In contrast, adult mice showed the opposite pattern; P2X1 levels were higher, and P2X7 levels decreased. These results suggest that adult mice are more vulnerable to repeated ketamine administration than young mice and that a differential response of P2X1 and P2X7 might contribute to ketamine-induced behavioral changes.
{"title":"Repeated administration of a subanesthetic dose of ketamine results in impaired motor and cognitive behavior and differential expression of hippocampal P2X1 and P2X7 receptors in adult mice","authors":"Teresa Belem Mares-Barbosa , Ares Orlando Cuellar-Santoyo , Victor Manuel Ruiz-Rodríguez , Karen Hernández-Balderas , Osiel González-Hernández , Diana Patricia Portales-Pérez , Ana María Estrada-Sánchez","doi":"10.1016/j.bbr.2025.115441","DOIUrl":"10.1016/j.bbr.2025.115441","url":null,"abstract":"<div><div>Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7). In the present study, we evaluated the effect of intraperitoneal administration of subanesthetic ketamine dose (30 mg/Kg) for fourteen days on young (35 days of age) and adult (76 days of age) mice on different behavioral tests. Nest-building behavior was evaluated during the fourteen-day treatment; short-term memory and social interaction tests were assessed twenty-four hours after the last administration of ketamine. Interestingly, only adult mice treated with ketamine showed impaired nest-building and novel object recognition<strong>.</strong> In the hippocampus, an area related to memory and cognition, ketamine administration showed no changes in the relative expression of GluN1, P2X4, and P2X7 while increasing GluA2 and P2X1 only in young mice. In contrast, when assessing the protein levels of P2X1 and P2X7 in the hippocampus following ketamine treatment, young mice exhibited a decrease in P2X1 levels while P2X7 levels increased. In contrast, adult mice showed the opposite pattern; P2X1 levels were higher, and P2X7 levels decreased. These results suggest that adult mice are more vulnerable to repeated ketamine administration than young mice and that a differential response of P2X1 and P2X7 might contribute to ketamine-induced behavioral changes.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"482 ","pages":"Article 115441"},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号