Brain communications最新文献

{"title":"Structural lesions and transcriptomic specializations shape gradient perturbations in Wilson disease.","authors":"Sheng Hu, Chuanfu Li, Yanming Wang, Taohua Wei, Xiaoxiao Wang, Ting Dong, Yulong Yang, Yufeng Ding, Bensheng Qiu, Wenming Yang","doi":"10.1093/braincomms/fcae329","DOIUrl":"10.1093/braincomms/fcae329","url":null,"abstract":"<p><p>Functional dysregulations in multiple regions are caused by excessive copper deposition in the brain in Wilson disease (WD) patients. The genetic mechanism of WD is thought to involve the abnormal expression of <i>ATP7B</i> in the liver, whereas the biological and molecular processes involved in functional dysregulation within the brain remain unexplored. The objective of this study was to unravel the underpinnings of functional gradient perturbations underlying structural lesions and transcriptomic specializations in WD. In this study, we included 105 WD patients and 93 healthy controls who underwent structural and functional MRI assessments. We used the diffusion mapping embedding model to derive the functional connectome gradient and further employed gray matter volume to uncover structure-function decoupling for WD. Then, we used Neurosynth, clinical data, and whole-brain gene expression data to examine the meta-analytic cognitive function, clinical phenotypes, and transcriptomic specializations related to WD gradient alterations. Compared with controls, WD patients exhibited global topographic changes in the principal pramary-to-transmodal gradient. Meta-analytic terms and clinical characteristics were correlated with these gradient alterations in motor-related processing, higher-order cognition, neurological symptoms, and age. Spatial correlations revealed structure-function decoupling in multiple networks, especially in subcortical and visual networks. Within the cortex, the spatial association between gradient alterations and gene expression profiles has revealed transcriptomic specilizations in WD that display properties indicative of ion homeostasis, neural development, and motor control. Furthermore, for the first time, we characterized the role of the <i>ATP7B</i> gene in impacting subcortical function. The transcriptomic specializations of WD were also associated with other neurological and psychiatric disorders. Finally, we revealed that structural lesions and gradient perturbations may share similar transcriptomic specializations in WD. In conclusion, these findings bridged functional gradient perturbations to structural lesions and gene expression profiles in WD patients, possibly promoting our understanding of the neurobiological mechanisms underlying the emergence of complex neurological and psychiatric phenotypes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Childhood anaesthesia and autism risk: population and murine study.","authors":"Mingyang Sun, Ningning Fu, Ting Li, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang","doi":"10.1093/braincomms/fcae325","DOIUrl":"10.1093/braincomms/fcae325","url":null,"abstract":"<p><p>Early childhood exposure to general anaesthesia has been linked to potential changes in infant brain morphology and behaviour in preclinical studies, contributing to long-term behaviours associated with autism spectrum disorder. This study investigates the association between early childhood exposure to general anaesthesia and the risk of autism, using a population-based cohort study with matching for baseline characteristics and evaluates the effect of sevoflurane exposure on autism-like behaviour in mice, using the Taiwan Maternal and Child Health Database. Children aged 0-3 who received at least one exposure to general anaesthesia between 2004 and 2014 were matched 1:1 with children who were not exposed. Risk ratios and confidence intervals were used to assess the relationship between general anaesthesia and the occurrence of autism. Additionally, mice were exposed to sevoflurane for 2 h on postnatal days 5-7, and changes in behaviour related to autism were evaluated. Propensity score matching resulted in 7530 children in each group. The incidence rates (IRs) of autism were 11.26 and 6.05 per 100 000 person-years in the exposed and unexposed groups, respectively. The incidence ratio for autism following exposure to general anaesthesia was 1.86 (95% confidence interval, 1.34-2.59). In mice, sevoflurane exposure induced autism-like behaviours and led to the downregulation of high-risk autism genes, including <i>ARID1B</i>, <i>GABRA5</i>, <i>GABRB3</i>, <i>GRIN2B</i>, <i>SHANK3</i> and <i>SUV420H1</i>. Early childhood exposure to general anaesthesia is associated with an increased risk of autism. Repeated exposure to sevoflurane in mice induces autism-like behaviours, suggesting a potential link between anaesthesia and the development of autism.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the prevalence of <i>MFN2</i> mutations in amyotrophic lateral sclerosis: insights from an Italian cohort.","authors":"Elena Abati, Delia Gagliardi, Arianna Manini, Roberto Del Bo, Dario Ronchi, Megi Meneri, Francesca Beretta, Annalisa Sarno, Federica Rizzo, Edoardo Monfrini, Alessio Di Fonzo, Maria Teresa Pellecchia, Alberto Brusati, Vincenzo Silani, Giacomo Pietro Comi, Antonia Ratti, Federico Verde, Nicola Ticozzi, Stefania Corti","doi":"10.1093/braincomms/fcae312","DOIUrl":"10.1093/braincomms/fcae312","url":null,"abstract":"<p><p>The <i>MFN2</i> gene encodes mitofusin 2, a key protein for mitochondrial fusion, transport, maintenance and cell communication. <i>MFN2</i> mutations are primarily linked to Charcot-Marie-Tooth disease type 2A. However, a few cases of amyotrophic lateral sclerosis and amyotrophic lateral sclerosis/frontotemporal dementia phenotypes with concomitant <i>MFN2</i> mutations have been previously reported. This study examines the clinical and genetic characteristics of an Italian cohort of amyotrophic lateral sclerosis patients with rare, non-synonymous <i>MFN2</i> mutations. A group of patients (<i>n</i> = 385) diagnosed with amyotrophic lateral sclerosis at our Neurology Units between 2008 and 2023 underwent comprehensive molecular testing, including <i>MFN2</i>. After excluding pathogenic mutations in the main amyotrophic lateral sclerosis-related genes (i.e. <i>C9orf72</i>, <i>SOD1</i>, <i>FUS</i> and <i>TARDBP</i>), <i>MFN2</i> variants were classified based on the American College of Medical Genetics and Genomics guidelines, and demographic and clinical data of <i>MFN2</i>-mutated patients were retrieved. We identified 12 rare, heterozygous, non-synonymous <i>MFN2</i> variants in 19 individuals (4.9%). Eight of these variants, carried by nine patients (2.3%), were either pathogenic, likely pathogenic or variants of unknown significance according to the American College of Medical Genetics and Genomics guidelines. Among these patients, four exhibited a familial pattern of inheritance. The observed phenotypes included classic and bulbar amyotrophic lateral sclerosis, amyotrophic lateral sclerosis/frontotemporal dementia, flail arm, flail leg and progressive muscular atrophy. Median survival after disease onset was extremely variable, ranging from less than 1 to 13 years. This study investigates the prevalence of rare, non-synonymous <i>MFN2</i> variants within an Italian cohort of amyotrophic lateral sclerosis patients, who have been extensively investigated, enhancing our knowledge of the underlying phenotypic spectrum. Further research is needed to understand whether <i>MFN2</i> mutations contribute to motor neuron disease and to what extent. Improving our knowledge regarding the genetic basis of amyotrophic lateral sclerosis is crucial both in a diagnostic and therapeutic perspective.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rehabilitating homonymous visual field deficits: white matter markers of recovery-stage 2 registered report.","authors":"Hanna E Willis, Bradley Caron, Matthew R Cavanaugh, Lucy Starling, Sara Ajina, Franco Pestilli, Marco Tamietto, Krystel R Huxlin, Kate E Watkins, Holly Bridge","doi":"10.1093/braincomms/fcae323","DOIUrl":"10.1093/braincomms/fcae323","url":null,"abstract":"<p><p>Damage to the primary visual cortex or its afferent white matter tracts results in loss of vision in the contralateral visual field that can present as homonymous visual field deficits. Evidence suggests that visual training in the blind field can partially reverse blindness at trained locations. However, the efficacy of visual training is highly variable across participants, and the reasons for this are poorly understood. It is likely that variance in residual neural circuitry following the insult may underlie the variation among patients. Many stroke survivors with visual field deficits retain residual visual processing in their blind field despite a lack of awareness. Previous research indicates that intact structural and functional connections between the dorsal lateral geniculate nucleus and the human extrastriate visual motion-processing area hMT+ are necessary for blindsight to occur. We therefore hypothesized that changes in this white matter pathway may underlie improvements resulting from motion discrimination training. Eighteen stroke survivors with long-standing, unilateral, homonymous field defects from retro-geniculate brain lesions completed 6 months of visual training at home. This involved performing daily sessions of a motion discrimination task, at two non-overlapping locations in the blind field, at least 5 days per week. Motion discrimination and integration thresholds, Humphrey perimetry and structural and diffusion-weighted MRI were collected pre- and post-training. Changes in fractional anisotropy (FA) were analysed in visual tracts connecting the ipsilesional dorsal lateral geniculate nucleus and hMT+, and the ipsilesional dorsal lateral geniculate nucleus and primary visual cortex. The (non-visual) tract connecting the ventral posterior lateral nucleus of the thalamus and the primary somatosensory cortex was analysed as a control. Changes in white matter integrity were correlated with improvements in motion discrimination and Humphrey perimetry. We found that the magnitude of behavioural improvement was not directly related to changes in FA in the pathway between the dorsal lateral geniculate nucleus and hMT+ or dorsal lateral geniculate nucleus and primary visual cortex. Baseline FA in either tract also failed to predict improvements in training. However, an exploratory analysis showed a significant increase in FA in the distal part of the tract connecting the dorsal lateral geniculate nucleus and hMT+, suggesting that 6 months of visual training in chronic, retro-geniculate strokes may enhance white matter microstructural integrity of residual geniculo-extrastriate pathways.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rehabilitating homonymous visual field deficits: white matter markers of recovery-stage 1 registered report.","authors":"Hanna E Willis, Matthew R Cavanaugh, Sara Ajina, Franco Pestilli, Marco Tamietto, Krystel R Huxlin, Kate E Watkins, Holly Bridge","doi":"10.1093/braincomms/fcae324","DOIUrl":"10.1093/braincomms/fcae324","url":null,"abstract":"<p><p>Damage to the primary visual cortex (V1) or its afferent white matter tracts results in loss of vision in the contralateral visual field that can present as homonymous visual field deficits. Recent evidence suggests that visual training in the blind field can partially reverse blindness at trained locations. However, the efficacy of visual training to improve vision is highly variable across subjects, and the reasons for this are poorly understood. It is likely that variance in residual functional or structural neural circuitry following the insult may underlie the variation among patients. Many patients with visual field deficits retain residual visual processing in their blind field, termed 'blindsight', despite a lack of awareness. Previous research indicates that an intact structural and functional connection between the dorsal lateral geniculate nucleus (dLGN) and the human extrastriate visual motion-processing area (hMT+) is necessary for blindsight to occur. We therefore predict that changes in this white matter pathway will underlie improvements in motion discrimination training. Twenty stroke survivors with unilateral, homonymous field defects from retro-geniculate brain lesions will complete 6 months of motion discrimination training at home. Visual training will involve performing two daily sessions of a motion discrimination task, at two non-overlapping locations in the blind field, at least 5 days per week. Motion discrimination and integration thresholds, Humphrey perimetry and structural and diffusion-weighted MRI will be collected pre- and post-training. Changes in fractional anisotropy will be analysed in two visual tracts: (i) between the ipsilesional dLGN and hMT+ and (ii) between the ipsilesional dLGN and V1. The (non-visual) tract between the ventral posterior lateral nucleus of the thalamus (VPL) and the primary somatosensory cortex (S1) will be analysed as a control. Tractographic changes will be compared to improvements in motion discrimination and Humphrey perimetry-derived metrics. We predict that (i) improved motion discrimination performance will be directly related to increased fractional anisotropy in the pathway between ipsilesional dLGN and hMT+ and (ii) improvements in Humphrey perimetry will be related to increased fractional anisotropy in the dLGN-V1 pathway. There should be no relationship between behavioural measures and changes in fractional anisotropy in the VPL-S1 pathway. This study has the potential to lead to greater understanding of the white matter microstructure of pathways underlying the behavioural outcomes resulting from visual training in retro-geniculate strokes. Understanding the neural mechanisms that underlie visual rehabilitation is fundamental to the development of more targeted and thus effective treatments for this underserved patient population.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain network changes after the first seizure: an insight into medication response?","authors":"Mangor Pedersen, Heath Pardoe, Remika Mito, Moksh Sethi, David N Vaughan, Patrick W Carney, Graeme D Jackson","doi":"10.1093/braincomms/fcae328","DOIUrl":"https://doi.org/10.1093/braincomms/fcae328","url":null,"abstract":"<p><p>After a first epileptic seizure, anti-seizure medications (ASMs) can change the likelihood of having a further event. This prospective study aimed to quantify brain network changes associated with taking ASM monotherapy. We applied graph theoretical network analysis to longitudinal resting-state functional MRI (fMRI) data from 28 participants who had recently experienced their first seizure. Participants were imaged before and during long-term ASM therapy, with a mean inter-scan interval of 6.9 months. After commencing ASM, we observed an increase in the clustering coefficient and a decrease in network path length. Brain changes after ASM treatment were most prominent in the superior frontoparietal and inferior fronto-temporal regions. Participants with recurrent seizures display the most pronounced network changes after ASM treatment. This study shows changes in brain network function after ASM administration, particularly in participants with recurrent seizures. Larger studies that ideally include control cohorts are required to understand further the connection between ASM-related brain network changes and longer-term seizure status.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compensation patterns and altered functional connectivity in alcohol use disorder with and without Korsakoff's syndrome.","authors":"Alexandrine Morand, Alice Laniepce, Nicolas Cabé, Céline Boudehent, Shailendra Segobin, Anne-Lise Pitel","doi":"10.1093/braincomms/fcae294","DOIUrl":"10.1093/braincomms/fcae294","url":null,"abstract":"<p><p>Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff's syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff's syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff's syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff's syndrome compared to alcohol use disorder without Korsakoff's syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff's syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff's syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff's syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients' overall lower cognitive performance. Korsakoff's syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volume-based structural connectome of epilepsy partialis continua in Rasmussen's encephalitis.","authors":"Cong Fu, Xue Yang, Mengyang Wang, Xiongfei Wang, Chongyang Tang, Guoming Luan","doi":"10.1093/braincomms/fcae316","DOIUrl":"10.1093/braincomms/fcae316","url":null,"abstract":"<p><p>Rasmussen's encephalitis is a rare, progressive neurological inflammatory with hemispheric brain atrophy. Epilepsy partialis continua (EPC) is a diagnostic clinical condition in patients with Rasmussen's encephalitis. However, the incidence of EPC in the natural course of Rasmussen's encephalitis is only about 50%. The majority of experts hold the belief that EPC is associated with dysfunction in the motor cortex, yet the whole pathogenesis remains unclear. We hypothesize that there is a characteristic topological discrepancy between groups with EPC and without EPC from the perspective of structural connectome. To this end, we described the structural MRI findings of 20 Rasmussen's encephalitis cases, 11 of which had EPC, and 9 of which did not have EPC (NEPC), and 20 healthy controls. We performed voxel-based morphometry to evaluate the alterations of grey matter volume. Using a volume-based structural covariant network, the hub distribution and modularity were studied at the group level. Based on the radiomic features, an individual radiomics structural similarity network was constructed for global topological properties, such as small-world index, higher path length, and clustering coefficient. And then, the Pearson correlation was used to delineate the association between duration and topology properties. In the both EPC and NEPC groups, the volume of the motor cortex on the affected side was significantly decreased, but putamen atrophy was most pronounced in the EPC group. Hubs in the EPC group consisted of the executive network, and the contralateral putamen was the hub in the NEPC group with the highest betweenness centrality. Compared to the NEPC, the EPC showed a higher path length and clustering coefficient in the structural similarity network. Moreover, the function of morphological network integration in EPC patients was diminished as the duration of Rasmussen's encephalitis increased. Our study indicates that motor cortex atrophy may not be directly related to EPC patients. Whereas atrophy of the putamen, and a more regularized configuration may contribute to the generation of EPC. The findings further suggest that the putamen could potentially serve as a viable target for controlling EPC in patients with Rasmussen's encephalitis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in cortical thickness: yet another indication of supraspinal adaptations in degenerative cervical myelopathy.","authors":"Aria Nouri, Granit Molliqaj, Karl Schaller, Enrico Tessitore","doi":"10.1093/braincomms/fcae322","DOIUrl":"10.1093/braincomms/fcae322","url":null,"abstract":"<p><p>This scientific commentary refers to 'Patterns of cortical thickness alterations in degenerative cervical myelopathy: associations with dexterity and gait dysfunctions', by Muhammad <i>et al</i>. (https://doi.org/10.1093/braincomms/fcae279).</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology.","authors":"Rin Yanai, Tomoki T Mitani, Etsuo A Susaki, Takeharu Minamihisamatsu, Masafumi Shimojo, Yuri Saito, Hiroshi Mizuma, Nobuhiro Nitta, Daita Kaneda, Yoshio Hashizume, Gen Matsumoto, Kentaro Tanemura, Ming-Rong Zhang, Makoto Higuchi, Hiroki R Ueda, Naruhiko Sahara","doi":"10.1093/braincomms/fcae326","DOIUrl":"https://doi.org/10.1093/braincomms/fcae326","url":null,"abstract":"<p><p>Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the <i>Rosa26</i> locus with a C57BL/6J background. This model closely mimics human tau pathology, particularly in the hippocampal CA1 region, showing age-dependent tau accumulation, neuronal loss and neuroinflammation. Notably, whole-brain 3D staining and light-sheet microscopy revealed a spatial gradient of tau deposition from the entorhinal cortex to the hippocampus, similar to the spatial distribution of Braak neurofibrillary tangle staging. Furthermore, [¹⁸F]PM-PBB3 positron emission tomography imaging enabled the quantification and live monitoring of tau deposition. The rTKhomo mouse model shows potential as a promising next-generation preclinical tool for exploring the mechanisms of tauopathy and for developing interventions targeting the spatial progression of tau pathology.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}