Pub Date : 2026-05-07Epub Date: 2026-03-07DOI: 10.1016/j.neuroscience.2026.03.008
Anke McLeod , Michael Rullmann , Philipp Hinderberger , Yvonne Böttcher , Ines Müller , Mohammed K. Hankir , Georg-Alexander Becker , Matthias Blüher , Ralf Regenthal , Anja Hilbert , Osama Sabri , Swen Hesse
A single nucleotide polymorphism in the brain derived neurotrophic factor (BDNF)-encoding gene leads to diminished BDNF signaling resulting from Val66Met and has been linked to obesity. Previous imaging studies regarding the impact of BDNF Val66Met on the central serotonin system, which is involved in behavior, cognition and control of satiety, have not focused on body weight or food-intake related behavior. We revisited a cohort of thirty non-depressed individuals with obesity and 15 normal-weight controls. 29 obese and 13 controls underwent [11C]DASB positron emission tomography imaging of the serotonin transporter (5-HTT), Val66Met genotyping and behavioral assessment with the Three-Factor Eating Questionnaire (TFEQ), which measures cognitive restraint, disinhibition and hunger. Volume-of-interest analyses were used to examine the influence of BDNF Val66Met on 5-HTT binding potential (BPND), BMI, and questionnaire scores. Compared to the homozygous Val/Val genotype, Met-carriers showed a significant increase of 5-HTT BPND in the medial prefrontal cortex. The data did not support a BDNF Val66Met effect on TFEQ measures, especially not on cognitive restraint. However, the construct of disinhibition and hunger correlated positively with BMI in homozygous Val-carriers while cognitive restraint did not. This study, despite its small sample size, indicates a possible dampening effect of BDNF Val66Met on prefrontal cortical serotonergic tone.
{"title":"BDNF Val66Met polymorphism is linked to elevated levels of serotonin-transporter in the medial prefrontal cortex but not to altered eating behavior","authors":"Anke McLeod , Michael Rullmann , Philipp Hinderberger , Yvonne Böttcher , Ines Müller , Mohammed K. Hankir , Georg-Alexander Becker , Matthias Blüher , Ralf Regenthal , Anja Hilbert , Osama Sabri , Swen Hesse","doi":"10.1016/j.neuroscience.2026.03.008","DOIUrl":"10.1016/j.neuroscience.2026.03.008","url":null,"abstract":"<div><div>A single nucleotide polymorphism in the brain derived neurotrophic factor (BDNF)-encoding gene leads to diminished BDNF signaling resulting from Val66Met and has been linked to obesity. Previous imaging studies regarding the impact of BDNF Val66Met on the central serotonin system, which is involved in behavior, cognition and control of satiety, have not focused on body weight or food-intake related behavior. We revisited a cohort of thirty non-depressed individuals with obesity and 15 normal-weight controls. 29 obese and 13 controls underwent [<sup>11</sup>C]DASB positron emission tomography imaging of the serotonin transporter (5-HTT), Val66Met genotyping and behavioral assessment with the Three-Factor Eating Questionnaire (TFEQ), which measures cognitive restraint, disinhibition and hunger. Volume-of-interest analyses were used to examine the influence of BDNF Val66Met on 5-HTT binding potential (BP<sub>ND</sub>), BMI, and questionnaire scores. Compared to the homozygous Val/Val genotype, Met-carriers showed a significant increase of 5-HTT BP<sub>ND</sub> in the medial prefrontal cortex. The data did not support a BDNF Val66Met effect on TFEQ measures, especially not on cognitive restraint. However, the construct of disinhibition and hunger correlated positively with BMI in homozygous Val-carriers while cognitive restraint did not. This study, despite its small sample size, indicates a possible dampening effect of BDNF Val66Met on prefrontal cortical serotonergic tone.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 148-154"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-03-09DOI: 10.1016/j.neuroscience.2026.03.006
Xue Shen , Xiaoyu Dong , Jianfei Nao
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, and cholinergic dysfunction. Currently, no disease-modifying drugs are available, and existing symptomatic treatments offer limited efficacy while posing safety concerns, highlighting the urgent need for multi‑target therapeutic strategies. The natural β‑carboline alkaloid harmine has attracted considerable attention due to its favorable blood–brain barrier penetration and multi‑target profile. Accumulating preclinical evidence indicates that harmine can concurrently modulate several core pathological processes of AD. Mechanistically, it potently inhibits dual‑specificity tyrosine phosphorylation‑regulated kinase 1A (DYRK1A), thereby reducing tau hyperphosphorylation, suppressing aberrant amyloid precursor protein processing, and enhancing neprilysin‑mediated Aβ clearance. Concurrently, harmine attenuates neuroinflammation via negative regulation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF‑κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, improves cholinergic neurotransmission through acetylcholinesterase inhibition, and alleviates glutamate excitotoxicity by upregulating astrocytic glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) expression. Structurally optimized harmine derivatives have demonstrated enhanced dual inhibitory activity and improved cognitive outcomes in preclinical models. Despite these promising findings, challenges such as pharmacokinetic limitations, insufficient target selectivity, and a lack of clinical data remain. In conclusion, the harmine scaffold represents a mechanistically grounded and promising direction for the development of multi‑target therapeutics for AD.
{"title":"Harmine and its derivatives: A promising multi-target therapeutic avenue for Alzheimer’s disease","authors":"Xue Shen , Xiaoyu Dong , Jianfei Nao","doi":"10.1016/j.neuroscience.2026.03.006","DOIUrl":"10.1016/j.neuroscience.2026.03.006","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, and cholinergic dysfunction. Currently, no disease-modifying drugs are available, and existing symptomatic treatments offer limited efficacy while posing safety concerns, highlighting the urgent need for multi‑target therapeutic strategies. The natural β‑carboline alkaloid harmine has attracted considerable attention due to its favorable blood–brain barrier penetration and multi‑target profile. Accumulating preclinical evidence indicates that harmine can concurrently modulate several core pathological processes of AD. Mechanistically, it potently inhibits dual‑specificity tyrosine phosphorylation‑regulated kinase 1A (DYRK1A), thereby reducing tau hyperphosphorylation, suppressing aberrant amyloid precursor protein processing, and enhancing neprilysin‑mediated Aβ clearance. Concurrently, harmine attenuates neuroinflammation via negative regulation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF‑κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, improves cholinergic neurotransmission through acetylcholinesterase inhibition, and alleviates glutamate excitotoxicity by upregulating astrocytic glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) expression. Structurally optimized harmine derivatives have demonstrated enhanced dual inhibitory activity and improved cognitive outcomes in preclinical models. Despite these promising findings, challenges such as pharmacokinetic limitations, insufficient target selectivity, and a lack of clinical data remain. In conclusion, the harmine scaffold represents a mechanistically grounded and promising direction for the development of multi‑target therapeutics for AD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 155-168"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-02-12DOI: 10.1016/j.neuroscience.2026.02.017
Minglong Li , Rong Guo , Miaomiao Liu , LuMeng Xu , Hongyu Ning , Jing Wang , Quanyuan Liu , Xianglin Li , Hongcai Wang
Glutamate accumulation linked to Parkinson’s disease (PD) pathogenesis. While glutamate chemical exchange saturation transfer (GluCEST) imaging has been applied in various CNS disorders, its utility in PD remains underexplored. This study investigated the clinical relevance of dentate nucleus and cerebellar hemisphere glutamate levels across PD motor subtypes. We enrolled 36 resting-tremor predominant PD (PDRT), 33 akinetic-rigid predominant PD (PDAR), and 40 healthy controls (HCs). GluCEST data were quantified via magnetization-transfer-ratio asymmetry (MTRasym) analysis, with four regions of interest (ROIs) manually delineated. Cerebellar volumetry was derived using the SUIT atlas. Results demonstrated significantly elevated MTRasym values in the dentate nucleus and cerebellar hemisphere of PDRT patients (*p*<0.05), indicative of increased glutamate concentrations. Concurrently, PDRT exhibited reduced cerebellar volumes compared to HCs, whereas PDAR showed no significant volumetric differences. These findings establish GluCEST as a sensitive, non-invasive biomarker for cerebellar glutamatergic pathology in PD. The subtype-specific metabolic disturbances imply distinct etiological mechanisms underlying tremor-dominant and akinetic-rigid phenotypes.
{"title":"Glutamate chemical exchange saturation transfer imaging reveals cerebellar glutamatergic alterations in Parkinson’s disease subtypes","authors":"Minglong Li , Rong Guo , Miaomiao Liu , LuMeng Xu , Hongyu Ning , Jing Wang , Quanyuan Liu , Xianglin Li , Hongcai Wang","doi":"10.1016/j.neuroscience.2026.02.017","DOIUrl":"10.1016/j.neuroscience.2026.02.017","url":null,"abstract":"<div><div>Glutamate accumulation linked to Parkinson’s disease (PD) pathogenesis. While glutamate chemical exchange saturation transfer (GluCEST) imaging has been applied in various CNS disorders, its utility in PD remains underexplored. This study investigated the clinical relevance of dentate nucleus and cerebellar hemisphere glutamate levels across PD motor subtypes. We enrolled 36 resting-tremor predominant PD (PDRT), 33 akinetic-rigid predominant PD (PDAR), and 40 healthy controls (HCs). GluCEST data were quantified via magnetization-transfer-ratio asymmetry (MTR<sub>asym</sub>) analysis, with four regions of interest (ROIs) manually delineated. Cerebellar volumetry was derived using the SUIT atlas. Results demonstrated significantly elevated MTR<sub>asym</sub> values in the dentate nucleus and cerebellar hemisphere of PDRT patients (*p*<0.05), indicative of increased glutamate concentrations. Concurrently, PDRT exhibited reduced cerebellar volumes compared to HCs, whereas PDAR showed no significant volumetric differences. These findings establish GluCEST as a sensitive, non-invasive biomarker for cerebellar glutamatergic pathology in PD. The subtype-specific metabolic disturbances imply distinct etiological mechanisms underlying tremor-dominant and akinetic-rigid phenotypes.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 58-68"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-02-21DOI: 10.1016/j.neuroscience.2026.02.034
Shiyu Wang , Kangqi Zhao , Zhen Li , Peiling Shi , Yi Deng , Qing Liu , Yongfeng Yang , Chuansheng Wang , Jie Li , Yuanbo Li , Luxain Lv , Wenqiang Li
Objective
The neurodevelopmental hypothesis of schizophrenia posits that early brain developmental abnormalities constitute its core pathological basis. However, the mechanisms by which environmental risk factors regulate specific molecular pathways, leading to long-term behavioral abnormalities, remain incompletely elucidated. This study aims to investigate whether maternal immune activation (MIA) disrupts the ASK1/MAPK signaling pathway in offspring during early development, alters neuronal apoptosis homeostasis, and ultimately mediates the emergence of schizophrenia-like phenotypes.
Methods
A MIA rat model was established. In offspring, at multiple postnatal developmental time points (P1, P7, P14, P21), the protein expression and phosphorylation levels of ASK1, p-p38, and p-JNK in the hippocampus and prefrontal cortex were detected. Additionally, the expression of apoptosis-related proteins Bax and Bcl-2 was measured. Neuronal structure was assessed using Nissl staining, and behavioral tests were performed.
Results
MIA offspring exhibited anxiety-like behaviors, cognitive deficits, and sensory gating impairments. The ASK1/MAPK pathway demonstrated spatiotemporal-specific disturbances: hippocampal ASK1 activity showed a triphasic dynamic abnormality, while the prefrontal cortex displayed biphasic suppression. These pathway disruptions were closely associated with brain region-specific imbalances in apoptosis homeostasis. The Bax/Bcl-2 ratio in the prefrontal cortex exhibited biphasic oscillations, whereas the hippocampus showed selective suppression of apoptotic activity at P7 and P21. Nissl staining further confirmed neuronal structural damage in MIA offspring.
Conclusion
This study first demonstrates that MIA induces spatiotemporal-specific ASK1/MAPK pathway disturbances, thereby altering neuronal apoptosis homeostasis during development and ultimately leading to neuronal structural damage and schizophrenia-like behavioral phenotypes. The differential mechanisms observed in the hippocampus and prefrontal cortex in response to MIA provide new experimental evidence for understanding the neurodevelopmental origins of schizophrenia, suggesting that the ASK1/MAPK pathway may serve as a critical bridge connecting early environmental stress with long-term neuropsychopathological phenotypes.
{"title":"Maternal immune activation impairs neurodevelopment in offspring via ASK1/MAPK-mediated apoptotic disruption during early development","authors":"Shiyu Wang , Kangqi Zhao , Zhen Li , Peiling Shi , Yi Deng , Qing Liu , Yongfeng Yang , Chuansheng Wang , Jie Li , Yuanbo Li , Luxain Lv , Wenqiang Li","doi":"10.1016/j.neuroscience.2026.02.034","DOIUrl":"10.1016/j.neuroscience.2026.02.034","url":null,"abstract":"<div><h3>Objective</h3><div>The neurodevelopmental hypothesis of schizophrenia posits that early brain developmental abnormalities constitute its core pathological basis. However, the mechanisms by which environmental risk factors regulate specific molecular pathways, leading to long-term behavioral abnormalities, remain incompletely elucidated. This study aims to investigate whether maternal immune activation (MIA) disrupts the ASK1/MAPK signaling pathway in offspring during early development, alters neuronal apoptosis homeostasis, and ultimately mediates the emergence of schizophrenia-like phenotypes.</div></div><div><h3>Methods</h3><div>A MIA rat model was established. In offspring, at multiple postnatal developmental time points (P1, P7, P14, P21), the protein expression and phosphorylation levels of ASK1, p-p38, and p-JNK in the hippocampus and prefrontal cortex were detected. Additionally, the expression of apoptosis-related proteins Bax and Bcl-2 was measured. Neuronal structure was assessed using Nissl staining, and behavioral tests were performed.</div></div><div><h3>Results</h3><div>MIA offspring exhibited anxiety-like behaviors, cognitive deficits, and sensory gating impairments. The ASK1/MAPK pathway demonstrated spatiotemporal-specific disturbances: hippocampal ASK1 activity showed a triphasic dynamic abnormality, while the prefrontal cortex displayed biphasic suppression. These pathway disruptions were closely associated with brain region-specific imbalances in apoptosis homeostasis. The Bax/Bcl-2 ratio in the prefrontal cortex exhibited biphasic oscillations, whereas the hippocampus showed selective suppression of apoptotic activity at P7 and P21. Nissl staining further confirmed neuronal structural damage in MIA offspring.</div></div><div><h3>Conclusion</h3><div>This study first demonstrates that MIA induces spatiotemporal-specific ASK1/MAPK pathway disturbances, thereby altering neuronal apoptosis homeostasis during development and ultimately leading to neuronal structural damage and schizophrenia-like behavioral phenotypes. The differential mechanisms observed in the hippocampus and prefrontal cortex in response to MIA provide new experimental evidence for understanding the neurodevelopmental origins of schizophrenia, suggesting that the ASK1/MAPK pathway may serve as a critical bridge connecting early environmental stress with long-term neuropsychopathological phenotypes.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 14-28"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-03-06DOI: 10.1016/j.neuroscience.2026.03.001
Shuo Wang , Yuqing Wei , Yongbiao Li , Hong Qing , Yan Yan , Yong Cheng
Neurodegenerative diseases are marked by progressive neuronal damage and currently lack a cure. Recently, exercise has emerged as a promising non-pharmacological approach to potentially slow disease progression and enhance cognitive function. This narrative review summarizes the effects of various exercise modalities—including aerobic exercise, resistance training, and balance training—on four major neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and spinocerebellar ataxia), as well as their underlying molecular mechanisms. Evidence from existing studies suggests that aerobic exercise activates the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis and supporting astrocyte function, which in turn reduces β-amyloid accumulation and neuroinflammation. Resistance and balance training primarily improve muscle strength and coordination, leading to better motor performance and quality of life. Additionally, exercise modulates the release of neurotrophic factors, enhancing synaptic plasticity and neurogenesis. The review also discusses optimal exercise protocols tailored to specific diseases, providing a foundation for clinical application and future research. Moving forward, studies should focus on personalized exercise regimens and long-term outcomes to maximize the benefits of non-pharmacological interventions in neurodegenerative diseases.
{"title":"Effects of different exercise modalities on four major neurodegenerative diseases and their molecular mechanisms","authors":"Shuo Wang , Yuqing Wei , Yongbiao Li , Hong Qing , Yan Yan , Yong Cheng","doi":"10.1016/j.neuroscience.2026.03.001","DOIUrl":"10.1016/j.neuroscience.2026.03.001","url":null,"abstract":"<div><div>Neurodegenerative diseases are marked by progressive neuronal damage and currently lack a cure. Recently, exercise has emerged as a promising non-pharmacological approach to potentially slow disease progression and enhance cognitive function. This narrative review summarizes the effects of various exercise modalities—including aerobic exercise, resistance training, and balance training—on four major neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and spinocerebellar ataxia), as well as their underlying molecular mechanisms. Evidence from existing studies suggests that aerobic exercise activates the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis and supporting astrocyte function, which in turn reduces β-amyloid accumulation and neuroinflammation. Resistance and balance training primarily improve muscle strength and coordination, leading to better motor performance and quality of life. Additionally, exercise modulates the release of neurotrophic factors, enhancing synaptic plasticity and neurogenesis. The review also discusses optimal exercise protocols tailored to specific diseases, providing a foundation for clinical application and future research. Moving forward, studies should focus on personalized exercise regimens and long-term outcomes to maximize the benefits of non-pharmacological interventions in neurodegenerative diseases.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 121-135"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-03-09DOI: 10.1016/j.neuroscience.2026.03.007
Fernando da Silva Fiorin , Man-Kyo Chung
Post-traumatic headache (PTH) lack effective treatment due to the wide variety of possible brain damage that can occur, as well as the neural mechanisms of pain. However, immunity and maladaptive plasticity are involved in many hyperalgesia states, including secondary headaches. While analgesic drugs can act on specific molecular pathways, headaches involve a complex system of pain. Physical exercise can be a potent nonpharmacological modulator of the immune system and is known to play an important role in neural plasticity. However, further studies are needed to better understand the beneficial effects of physical exercise on secondary headaches and how physical exercise, the immune system, and plasticity interact with PTH. Here, we examine how immune system–induced neuroplasticity contributes to headache pathophysiology and how physical exercise might reverse these maladaptive changes.
{"title":"The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache","authors":"Fernando da Silva Fiorin , Man-Kyo Chung","doi":"10.1016/j.neuroscience.2026.03.007","DOIUrl":"10.1016/j.neuroscience.2026.03.007","url":null,"abstract":"<div><div>Post-traumatic headache (PTH) lack effective treatment due to the wide variety of possible brain damage that can occur, as well as the neural mechanisms of pain. However, immunity and maladaptive plasticity are involved in many hyperalgesia states, including secondary headaches. While analgesic drugs can act on specific molecular pathways, headaches involve a complex system of pain. Physical exercise can be a potent nonpharmacological modulator of the immune system and is known to play an important role in neural plasticity. However, further studies are needed to better understand the beneficial effects of physical exercise on secondary headaches and how physical exercise, the immune system, and plasticity interact with PTH. Here, we examine how immune system–induced neuroplasticity contributes to headache pathophysiology and how physical exercise might reverse these maladaptive changes.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 104-120"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-02-28DOI: 10.1016/j.neuroscience.2026.02.046
Shan Liu , Rui Li , Fei Wang , Yan Wang , Ke Liu
To investigate whether cochlear progenitor cell transplantation into the inner ear can restore kanamycin-induced acute ototoxic sensorineural hearing loss, we established an acute ototoxic injury model via intraperitoneal injection of kanamycin and a diuretic. Cell transplantation was performed on the fifth day after model establishment. Two weeks post-transplantation, auditory brainstem response (ABR) testing assessed hearing recovery in mice. Subsequently, immunofluorescence staining of mouse cochleae analyzed the distribution and engraftment of transplanted cochlear stem cells within the inner ear. Results demonstrated that kanamycin caused acute loss of outer hair cells while significantly elevating hearing thresholds. Following cell transplantation, cochlear progenitor cells predominantly distributed in the scala tympani beneath the basilar membrane, with a small number colonizing the scala media. Concurrently, hearing thresholds partially recovered in transplanted mice. Collectively, these findings demonstrate that transplanted cochlear progenitor cells can survive and colonize within the cochlea, partially restoring hearing in mice with acute ototoxic damage.
{"title":"Inner ear transplantation of cochlear progenitor cells restores acute sensorineural hearing loss","authors":"Shan Liu , Rui Li , Fei Wang , Yan Wang , Ke Liu","doi":"10.1016/j.neuroscience.2026.02.046","DOIUrl":"10.1016/j.neuroscience.2026.02.046","url":null,"abstract":"<div><div>To investigate whether cochlear progenitor cell transplantation into the inner ear can restore kanamycin-induced acute ototoxic sensorineural hearing loss, we established an acute ototoxic injury model via intraperitoneal injection of kanamycin and a diuretic. Cell transplantation was performed on the fifth day after model establishment. Two weeks post-transplantation, auditory brainstem response (ABR) testing assessed hearing recovery in mice. Subsequently, immunofluorescence staining of mouse cochleae analyzed the distribution and engraftment of transplanted cochlear stem cells within the inner ear. Results demonstrated that kanamycin caused acute loss of outer hair cells while significantly elevating hearing thresholds. Following cell transplantation, cochlear progenitor cells predominantly distributed in the scala tympani beneath the basilar membrane, with a small number colonizing the scala media. Concurrently, hearing thresholds partially recovered in transplanted mice. Collectively, these findings demonstrate that transplanted cochlear progenitor cells can survive and colonize within the cochlea, partially restoring hearing in mice with acute ototoxic damage.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 37-44"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-02-28DOI: 10.1016/j.neuroscience.2026.02.044
Fábio Lobato , Jéssica Leite , Antonio Jacob Jr. , Roberto Santana
Advances in connectomics and the characterization of neuronal diversity have been fundamental to understanding how the brain works. Defining a taxonomy is still challenging and requires complex computational methods. In this paper, we present a systematic review of the state-of-the-art methods for neuronal morphology classification, shedding light on trends and future directions. We address three core research questions: (1) What computational methods are used to classify neuronal morphologies? (2) What kind of representation do the classification models work on? (3) How are the classification models evaluated? We applied a structured protocol including peer-reviewed studies published since 2018. We collected 840 papers from five databases, published between 2018 and 2024. We assessed risk of bias using predefined quality criteria on study design, methodology, and reporting; 35 studies met these standards and were included to extract information and consolidate the results. The results show that Artificial Neural Networks are currently the main method for classifying neurons based on morphometric features (21 papers). Representations based on microscopy images for extracting morphometric features (30) are commonly used. Accuracy (29) is the predominant evaluation measure. Our research findings contribute to the body of knowledge by providing an up-to-date perspective on neuronal classification, which can guide future research in neuroscience and related fields.
{"title":"In silico neuronal morphology classification: A systematic review","authors":"Fábio Lobato , Jéssica Leite , Antonio Jacob Jr. , Roberto Santana","doi":"10.1016/j.neuroscience.2026.02.044","DOIUrl":"10.1016/j.neuroscience.2026.02.044","url":null,"abstract":"<div><div>Advances in connectomics and the characterization of neuronal diversity have been fundamental to understanding how the brain works. Defining a taxonomy is still challenging and requires complex computational methods. In this paper, we present a systematic review of the state-of-the-art methods for neuronal morphology classification, shedding light on trends and future directions. We address three core research questions: (1) What computational methods are used to classify neuronal morphologies? (2) What kind of representation do the classification models work on? (3) How are the classification models evaluated? We applied a structured protocol including peer-reviewed studies published since 2018. We collected 840 papers from five databases, published between 2018 and 2024. We assessed risk of bias using predefined quality criteria on study design, methodology, and reporting; 35 studies met these standards and were included to extract information and consolidate the results. The results show that Artificial Neural Networks are currently the main method for classifying neurons based on morphometric features (21 papers). Representations based on microscopy images for extracting morphometric features (30) are commonly used. Accuracy (29) is the predominant evaluation measure. Our research findings contribute to the body of knowledge by providing an up-to-date perspective on neuronal classification, which can guide future research in neuroscience and related fields.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 83-103"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-03-03DOI: 10.1016/j.neuroscience.2026.02.047
Enis Guso , Alessia Lupoli , Emanuele Olivieri , Alessia Bottoni , Maira Gironi , Davide M. Missarelli , Ahmed T. Toosy , Elena Rossi , Roberto Furlan
Trained immunity is the ability of the innate immune system to mount a heightened response to an environmental stimulus after a previous encounter with a noxious trigger. This effect is mediated by metabolic rewiring and epigenetic reprogramming in innate immune cells. In the context of neuroinflammation, trained immunity may represent a major contributor to the pathogenesis of neurological diseases, exerting both detrimental and potentially beneficial effects. While the general mechanisms and systemic implications of trained immunity are widely discussed, evidence in central nervous system (CNS) diseases remains fragmented and largely confined to individual pathological conditions. As a result, a comprehensive framework integrating these findings and identifying shared mechanisms across neurological disorders is still lacking. In this review, we explore the concept of trained immunity with a focus on neuroinflammatory and neurodegenerative diseases, synthetizing evidence from multiple CNS pathologies, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and cerebrovascular disorders. We first critically examine preclinical and experimental studies addressing innate immune memory in the CNS and subsequently integrate these findings with emerging clinical evidence, aiming to identify convergent mechanisms and disease-relevant immune memory signatures. Finally, we discuss potential therapeutic targets identified in preclinical settings and outline key unresolved issues, including the nature of triggering stimuli, thresholds, and temporal dynamics shaping innate immune memory in the CNS. By highlighting current limitations and defining critical questions for future research, this review presents a unifying perspective on trained immunity in neurological diseases and underscores the translational potential to modulate neuroinflammation and to influence disease progression.
{"title":"Trained immunity in neuroinflammation: emerging evidence, clinical perspectives, and future directions","authors":"Enis Guso , Alessia Lupoli , Emanuele Olivieri , Alessia Bottoni , Maira Gironi , Davide M. Missarelli , Ahmed T. Toosy , Elena Rossi , Roberto Furlan","doi":"10.1016/j.neuroscience.2026.02.047","DOIUrl":"10.1016/j.neuroscience.2026.02.047","url":null,"abstract":"<div><div>Trained immunity is the ability of the innate immune system to mount a heightened response to an environmental stimulus after a previous encounter with a noxious trigger. This effect is mediated by metabolic rewiring and epigenetic reprogramming in innate immune cells. In the context of neuroinflammation, trained immunity may represent a major contributor to the pathogenesis of neurological diseases, exerting both detrimental and potentially beneficial effects. While the general mechanisms and systemic implications of trained immunity are widely discussed, evidence in central nervous system (CNS) diseases remains fragmented and largely confined to individual pathological conditions. As a result, a comprehensive framework integrating these findings and identifying shared mechanisms across neurological disorders is still lacking. In this review, we explore the concept of trained immunity with a focus on neuroinflammatory and neurodegenerative diseases, synthetizing evidence from multiple CNS pathologies, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and cerebrovascular disorders. We first critically examine preclinical and experimental studies addressing innate immune memory in the CNS and subsequently integrate these findings with emerging clinical evidence, aiming to identify convergent mechanisms and disease-relevant immune memory signatures. Finally, we discuss potential therapeutic targets identified in preclinical settings and outline key unresolved issues, including the nature of triggering stimuli, thresholds, and temporal dynamics shaping innate immune memory in the CNS. By highlighting current limitations and defining critical questions for future research, this review presents a unifying perspective on trained immunity in neurological diseases and underscores the translational potential to modulate neuroinflammation and to influence disease progression.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 45-57"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-07Epub Date: 2026-03-02DOI: 10.1016/j.neuroscience.2026.02.048
Danil A. Lukovikov , Ilya S. Zhukov , Elena V. Gerasimova , Konstantin A. Demin , Raul R. Gainetdinov , Natalia V. Alenina , Tatiana O. Kolesnikova , Pavel E. Musienko
Rodent models are essential in neuroscience research for investigating brain function, CNS disease mechanisms, and therapeutic interventions. Beyond molecular and physiological analyses, precise behavioral characterization provides crucial functional readouts of neural circuit changes. Accurate behavioral phenotyping is critical for detecting genotype-phenotype relationships, enabling cross-model comparisons, and supporting translational research. Here we developed a machine learning framework for automated rodent behavior analysis in the Cylinder Exploration Test (CET) using pose estimation and explainable machine learning. The framework quantifies freezing, rearing, exploratory movement, and general locomotion activity while identifying key behavioral features that differentiate between experimental conditions. To validate this approach, we phenotyped two rat strains with dopaminergic and serotonergic dysfunction: dopamine transporter knockout (DAT-KO), tryptophan hydroxylase 2 knockout (Tph2-KO), and their wild-type controls. The analysis successfully identified distinct strain-specific behavioral phenotypes and characterized the discriminative features between genotypes, achieving high classification accuracy (AUC = 0.84 for DAT-KO versus DAT-WT and AUC = 0.98 for Tph2-KO versus Tph2-WT). These findings demonstrate that automated Cylinder Exploration Test can detect genotype-specific signatures and establish a scalable method for standardized phenotyping in neuroscience and preclinical research.
{"title":"Automated phenotyping of rodent behavior in the Cylinder Exploration Test using machine learning","authors":"Danil A. Lukovikov , Ilya S. Zhukov , Elena V. Gerasimova , Konstantin A. Demin , Raul R. Gainetdinov , Natalia V. Alenina , Tatiana O. Kolesnikova , Pavel E. Musienko","doi":"10.1016/j.neuroscience.2026.02.048","DOIUrl":"10.1016/j.neuroscience.2026.02.048","url":null,"abstract":"<div><div>Rodent models are essential in neuroscience research for investigating brain function, CNS disease mechanisms, and therapeutic interventions. Beyond molecular and physiological analyses, precise behavioral characterization provides crucial functional readouts of neural circuit changes. Accurate behavioral phenotyping is critical for detecting genotype-phenotype relationships, enabling cross-model comparisons, and supporting translational research. Here we developed a machine learning framework for automated rodent behavior analysis in the Cylinder Exploration Test (CET) using pose estimation and explainable machine learning. The framework quantifies freezing, rearing, exploratory movement, and general locomotion activity while identifying key behavioral features that differentiate between experimental conditions. To validate this approach, we phenotyped two rat strains with dopaminergic and serotonergic dysfunction: dopamine transporter knockout (DAT-KO), tryptophan hydroxylase 2 knockout (Tph2-KO), and their wild-type controls. The analysis successfully identified distinct strain-specific behavioral phenotypes and characterized the discriminative features between genotypes, achieving high classification accuracy (AUC = 0.84 for DAT-KO versus DAT-WT and AUC = 0.98 for Tph2-KO versus Tph2-WT). These findings demonstrate that automated Cylinder Exploration Test can detect genotype-specific signatures and establish a scalable method for standardized phenotyping in neuroscience and preclinical research.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"601 ","pages":"Pages 169-178"},"PeriodicalIF":2.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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