Cerebellum最新文献

{"title":"Brainstem Substructure Atrophy in Late-Onset GM2-Gangliosidosis Imaging Using Automated Segmentation.","authors":"Olivia E Rowe, D Rangaprakash, Florian S Eichler, Jeremy D Schmahmann, Robert L Barry, Christopher D Stephen","doi":"10.1007/s12311-025-01803-4","DOIUrl":"10.1007/s12311-025-01803-4","url":null,"abstract":"<p><p>Late-Onset GM2-Gangliosidoses (LOGG) are rare, neurodegenerative lysosomal disorders that include late-onset Tay-Sachs (LOTS) and Sandhoff disease (LOSD) subtypes. Cerebellar atrophy is common, even in the absence of clinical ataxia, particularly in LOTS. Recent reports have also described brainstem atrophy in LOTS. We assessed brainstem substructure atrophy in LOGG, including LOSD. 10 LOGG patients (7 LOTS, 3 LOSD) and 7 age-matched controls had structural MRI brain imaging. A FreeSurfer brainstem substructure module was used for automatic segmentation and included the pons, medulla, superior cerebellar peduncle (SCP), midbrain, and total brainstem. Clinical ataxia severity was assessed with the LOTS Severity Scale, Brief Ataxia Rating Scale, Friedreich's Ataxia Rating Scale and Scale for the Assessment and Rating of Ataxia. There were differences between LOGG and controls in the pons (12,785.06 ± 1,603.84 vs. 15,457.14 ± 2,748.41 mm³, p = 0.0069) and SCP (196.93 ± 31.20 vs. 293.57 ± .70.16 mm³, p = 0.0003). In LOTS vs. controls, there was similar pons (p = 0.0055) and SCP atrophy (p = 0.0023). The LOSD group was too small for independent comparisons. There were no significant associations between SCP/pons volume and clinical scales or disease duration. Cerebellar volume, which was analyzed in a previous study by Rowe et al. (2021), was relatively preserved in LOSD compared to the SCP/pons, while in LOTS, the pontocerebellar atrophy profile was dominated by cerebellar atrophy. These findings provide anatomical and clinical insights to the cerebellar/brainstem atrophy observed in LOGG and highlight a need to stratify LOGG by subtypes.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"50"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomics-based Modelling Unveils Cerebellar Involvement in Parkinson's Disease.","authors":"Yini Chen, Yiwei Qi, Yiying Hu, Tao Qiu, Meichen Liu, Qiqi Jia, Yubing Sun, Xinhui Qiu, Bo Sun, Zhanhua Liang, Weidong Le, Tianbai Li","doi":"10.1007/s12311-025-01797-z","DOIUrl":"10.1007/s12311-025-01797-z","url":null,"abstract":"<p><p>Emerging pathological and neurophysiological evidence has highlighted the cerebellum's involvement in Parkinson's disease (PD). This study aimed to explore the potential of cerebellum-derived magnetic resonance imaging (MRI) radiomics in distinguishing PD patients from healthy controls (HC). A retrospective analysis was conducted using three-dimensional-T1 MRI data (n= 374) from the Parkinson's Progression Markers Initiative (PPMI) dataset (n= 204) and an independent in-house cohort (n= 170). Radiomic features (n= 883) were extracted from the cerebellar gray and white matter of each individual. Three machine learning models were developed: a cerebellar gray matter model, a cerebellar white matter model, and a combined gray and white matter model, to classify PD patients and HC. The results showed that the cerebellar gray matter model achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.931 in the training set, with a sensitivity of 60.8% and specificity of 97.1%, while in the testing set, it obtained an AUC of 0.874, with a sensitivity of 86.1% and specificity of 62.6%. The white matter-based model demonstrated an AUC of 0.846 (sensitivity, 59.8%; specificity, 87.3%) in the training set and an AUC of 0.868 (sensitivity, 81.0%; specificity, 75.8%) in the testing set. Notably, the combined gray and white matter model exhibited superior performance, achieving an AUC of 0.936 (sensitivity, 65.7%; specificity, 96.1%) in the training set and an AUC of 0.881 (sensitivity, 82.3%; specificity, 63.7%) in the testing set. Key radiomic features contributing to PD classification included Gray-level Dependence Matrix, Gray-level Co-occurrence Matrix and First-Order from gray matter, as well as Gray-level Size Zone Matrix from white matter, highlighting significant radiomics changes in the cerebellum associated with PD. In conclusion, this study demonstrates that MRI radiomics of cerebellar gray and white matter can effectively differentiate PD patients from HC, supporting the cerebellum's pivotal role in PD pathology and its potential as an imaging biomarker for PD.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"48"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442676","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}

{"title":"Differential Protective Effects of Edaravone in Cerebellar and Hippocampal Ischemic Injury Models.","authors":"Jens Dickmeiß, Yoshiyuki Henning, Sarah Stahlke, Thomas Weber, Carsten Theiss, Veronika Matschke","doi":"10.1007/s12311-025-01804-3","DOIUrl":"10.1007/s12311-025-01804-3","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of mortality and disability, with cerebellar strokes posing severe complications such as herniation and brainstem compression. Edaravone, a radical scavenger known for reducing oxidative stress, has shown neuroprotective effects in cerebral strokes, but its impact on cerebellar strokes remains unclear. This study investigates Edaravone's protective properties in organotypic slice cultures of rat cerebellum and hippocampus, employing an oxygen-glucose deprivation (OGD) model to simulate ischemic stroke. The hippocampus served as comparative structure due to its high hypoxia sensitivity. Our results confirmed effective hypoxic induction with increases in HIF-1α and HIF-2α expression. Edaravone significantly reduced lactate dehydrogenase (LDH) levels, indicating diminished cellular damage, with cerebellar tissues showing greater vulnerability. Additionally, Edaravone reduced reactive oxygen species (ROS) in both tissues, though its efficacy may be limited by higher oxidative stress in cerebellar cultures. Seahorse XF analysis revealed that Edaravone preserved mitochondrial respiration and tissue integrity in cerebellar and hippocampal slice cultures. However, Edaravone was more effective in preserving mitochondrial respiration in hippocampal slices, suggesting that OGD-induced damage is more severe in cerebellar tissue. In conclusion, Edaravone demonstrates significant cell protective effects in both cerebellar and hippocampal tissues under OGD conditions, preserving tissue integrity and enhancing mitochondrial function in a tissue-dependent manner. These findings suggest Edaravone as a promising therapeutic candidate for cerebellar stroke. Further in vivo studies are required to assess its full clinical potential.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"49"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cerebellar Role in Emotions at a Turning Point: Bibliometric Analysis and Collaboration Networks.","authors":"Dianela A Osorio-Becerra, Egidio D'Angelo, Claudia Casellato","doi":"10.1007/s12311-025-01800-7","DOIUrl":"10.1007/s12311-025-01800-7","url":null,"abstract":"<p><p>The neural basis of emotional experience, both in neurotypical and clinical conditions, remains an open research topic. Historically, the cerebellum was considered a purely motor structure; however, studies since the mid-twentieth century and contributions like the cerebellar cognitive-affective syndrome, evidenced its role in emotion. This has led to an expansion of the paradigm, encouraging further research into the cerebellar role in emotion. Understanding this field's development is essential to assessing its current state, identifying knowledge gaps, and exploring emerging areas. This paper analyzes the evolution of scientific production, addressing how scientific interest has changed over time, factors driving growth, dominant topics, leading figures, and collaboration networks. This analysis identifies trends and opportunities, guiding strategies and advancing knowledge through a comprehensive view of the state-of-the-art in this research area. To achieve this, a systematic search was conducted in key databases, identifying 1,162 publications with which an exhaustive quantitative analysis was conducted using bibliometric techniques, network analysis, and visualization tools. The results show exponential growth in the field, evidenced by the increase in publications, researchers, funding sources, and the emergence of new topics. This interest, along with an interdisciplinary approach, has fostered collaboration, with large teams and multicenter projects emerging, although small, isolated teams still predominate. Research mainly focuses on neurological and affective disorders, with a predominance of studies in humans, followed by rodent models. Overall, the analysis reveals a highly interdisciplinary and expanding field. However, challenges remain, including unequal access to resources and limited exploration of some topics.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"47"},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar Neuromodulation in Autism Spectrum Disorders and Social Cognition: Insights from Animal and Human Studies.","authors":"Yannis Elandaloussi, Océane Dufrenne, Aline Lefebvre, Josselin Houenou, Suhan Senova, Charles Laidi","doi":"10.1007/s12311-025-01801-6","DOIUrl":"10.1007/s12311-025-01801-6","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by social atypicalities and repetitive behaviors. Growing evidence suggests that alterations in brain networks may contribute to ASD symptoms. The cerebellum, with its widespread connections to the cortex, has emerged as a potential key player in ASD. Non-invasive neuromodulation techniques, such as transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) offer a promising avenue for modulating brain activity and potentially alleviating ASD symptoms. In addition, preclinical studies in rodents further emphasize the therapeutic effect of cerebellar stimulation to target autism-related symptoms. This article reviews both clinical and preclinical studies aiming to modulate cerebellar circuits to improve symptoms of ASD. We found ten relevant studies assessing the effect of cerebellar neuromodulation in human and preclinical models. Posterior cerebellar tDCS represented the most frequent neuromodulation method and suggested that cerebellar tDCS can lead to improvements in symptoms of ASD and restore cerebellar connectivity in individuals with ASD. In neurotypical participants, there is evidence that cerebellar tDCS can enhance social cognitive abilities. These results are in line with preclinical studies, suggesting that chemogenetic stimulation can modulate cerebellar circuits involved in ASD and improve related behaviors. Further research is needed to establish standardized protocols, assess long-term effects, and investigate the underlying mechanisms of cerebellar stimulation. We examine research questions that need to be addressed before launching large scale randomized clinical trials.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"46"},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400513","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}

{"title":"Demystifying the Etiology of ILOCA in the Genomic Era: A Narrative Review.","authors":"Luiz Eduardo Novis, Thiago Yoshinaga Tonholo Silva, José Luiz Pedroso, Orlando Graziani Póvoas Barsottini","doi":"10.1007/s12311-025-01798-y","DOIUrl":"10.1007/s12311-025-01798-y","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Late-Onset Cerebellar Ataxia (ILOCA) is a challenging and heterogeneous disorder characterized by progressive cerebellar ataxia beginning after the age of 40 without a family history of cerebellar ataxia. Despite extensive investigations, many cases remain undiagnosed. The advent Next Generation Sequencing (NGS) has significantly advanced the identification of genetic causes associated with ILOCA.</p><p><strong>Objective: </strong>This study aims to review the concept of ILOCA, its historical perspective, epidemiology, diagnostic criteria, and the impact of the new era of genetic diagnosis facilitated by NGS technologies.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted, focusing on the genetic advancements in diagnosing ILOCA.</p><p><strong>Results: </strong>ILOCA accounts for a significant proportion of late-onset cerebellar ataxias. The prevalence of late-onset cerebellar ataxias ranges from 2.2 to 12.4 per 100,000 individuals, with genetic causes identified in up to 30-50% of cases using NGS. Key genetic findings include repeat expansion disorders such as Spinocerebellar Ataxia type 27 B, Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome and Friedreich Ataxia. SCAs and Autosomal Recessive Cerebellar Ataxia caused by point mutations are also frequently observed in large cohorts. Advances in NGS have increased the diagnostic yield for ILOCA.</p><p><strong>Conclusion: </strong>ILOCA represents a significant diagnostic challenge due to its heterogeneous nature and the overlap with other neurodegenerative and genetic conditions. The use of NGS technologies has revolutionized the diagnostic approach, uncovering genetic causes in a substantial number of previously undiagnosed cases. Routine investigation of specific genes associated with ILOCA is recommended to improve diagnostic accuracy and patient management.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"45"},"PeriodicalIF":2.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371332","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}

{"title":"Novel Intermediate ATXN10 Alleles in the Healthy Peruvian Population: A Matter of Indigenous American Ethnic Origin.","authors":"Karina Milla-Neyra, Ismael Araujo-Aliaga, Carla Manrique-Enciso, Elison Sarapura-Castro, Maryenela Illanes-Manrique, Diego Veliz-Otani, Ana Saldarriaga-Mayo, Angel Medina-Colque, Julia Rios-Pinto, Ivan Cornejo-Herrera, Andrea Rivera-Valdivia, Ignacio F Mata, Douglas Loesch, Leonel Lozano-Vasquez, Tanuja Bordia, Timothy O'Connor, Birgitt Schüle, Mario Cornejo-Olivas","doi":"10.1007/s12311-025-01795-1","DOIUrl":"10.1007/s12311-025-01795-1","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease predominant in Latin American individuals with Indigenous American ancestry. SCA10 is caused by an expansion of ATTCT repeat within the ATXN10 gene. Healthy individuals carry 9-32 ATTCT repeats, whereas SCA10 patients carry an expansion of 280 repeats and higher. Recently, intermediate alleles (over than 32 repeats) have been identified in healthy Peruvian Indigenous American individuals, with unclear significance. This study aims to characterize the variability of the ATTCT repeats within the ATXN10 gene across self-declared Indigenous American and Mestizo subpopulations from Peru. A total of 871 samples (754 Mestizo and 117 Indigenous American) were analyzed using PCR, and RP-PCR when suspecting apparent homozygosity due to larger alleles. 8.7% of the total of healthy individuals (76/871) carry at least one intermediate allele. The 14-repeat allele being the most common for both subpopulations (41.5%). Intermediate alleles were detected in the Peruvian population (4.5%) with a significantly higher frequency among self-declared Indigenous American compared to Mestizo, suggesting a possible association with the ethnic origin. The G allele at the SNP rs41524547 had a frequency of 51.39% in individuals with intermediate alleles, with not significantly difference between subpopulations. Further analysis should be performed to confirm the size and composition of ATTCT repeat tract, as well as the contribution of rs41524547 in SCA10.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"44"},"PeriodicalIF":2.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366634","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}

{"title":"Hyperconnectivity and Connectome Gradient Dysfunction of Cerebello-Thalamo-Cortical Circuitry in Alzheimer's Disease Spectrum Disorders.","authors":"Chenyang Yao, Yi Shan, Bixiao Cui, Zhigeng Chen, Sheng Bi, Tao Wang, Shaozhen Yan, Jie Lu","doi":"10.1007/s12311-025-01792-4","DOIUrl":"10.1007/s12311-025-01792-4","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cerebellar functional connectivity changes have been reported in Alzheimer's disease (AD), but a comprehensive framework integrating these findings is lacking. This retrospective study investigates the cerebello-thalamo-cortical (CTC) circuit in AD, using functional gradient analysis to elucidate deficits and potential biomarkers. We analyzed data from 246 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI-3; NCT02854033), including 58 with AD, 103 with mild cognitive impairment (MCI), and 85 cognitively normal (CN) controls, matched for age and sex. All individuals underwent comprehensive neuropsychological assessments (MMSE, MoCA, ADAS-Cog) and MRI scans. We extracted mean time series for 270 brain regions (an extended Power atlas) and computed pairwise functional connectivity, focusing on CTC circuitry. Thalamic and cerebellar connectivity gradients were derived using voxel-wise correlation matrices and the BrainSpace toolbox, defining thalamic and cerebellar masks from the Melbourne subcortical atlas and AAL atlas, respectively. ANCOVA with post hoc analyses, controlling for age and sex, was conducted to assess abnormal CTC connectivity across AD, MCI, and CN groups. LASSO regression identified edges within the CTC circuitry that significantly differed between AD and CN, MCI and CN, AD and MCI, as well as was used to construct Logistic classification model. Pearson correlations were performed to examine relationships between mean CTC connectivity, individual edges, and cognitive scores (MMSE, MoCA, ADAS-Cog). To explore the hierarchical organization of the thalamus and cerebellum, global gradient distributions were compared across groups using two-sample Kolmogorov-Smirnov tests. Additionally, ANCOVA was applied to compare subfield- and functional-level gradients of the thalamus and cerebellum among AD, MCI, and CN. False discovery rate (FDR) corrections were used, setting the statistical significance threshold was set at P &lt; 0.05. AD and MCI individuals exhibited increased CTC connectivity compared to CN (all P &lt; 0.05). Average CTC connectivity did not correlate with cognitive scores (P &gt; 0.05), but specific CTC edges were correlated. LASSO regression identified 20 discriminative edges, achieving high accuracy in AD-CN classification (AUC = 0.92 training, AUC = 0.80 test). Thalamic and cerebellar gradient distributions differed significantly across groups (all P &lt; 0.05), with specific regions showing distinct gradient scores. Five cerebellar functional networks exhibited decreased gradient scores. Significant CTC hyperconnectivity in AD and MCI compared with CN suggests early thalamic and cerebellar dysregulation. Classification analyses effectively distinguished AD vs. CN but were moderate for MCI vs. CN and limited for MCI vs. AD. Gradient analyses revealed global- and subfield-level disruptions in AD, emphasizing the role of thalamic and cerebellar interactions in cognitive decline and offering potential ","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"43"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257322","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}

{"title":"Functional Characterization of Parallel Fiber-Purkinje Cell Synapses in Two Friedreich's Ataxia Mouse Models.","authors":"Donald J Joseph, Elizabeth Mercado-Ayon, Liam Flatley, Angela N Viaene, Juliette Hordeaux, Eric D Marsh, David R Lynch","doi":"10.1007/s12311-025-01796-0","DOIUrl":"10.1007/s12311-025-01796-0","url":null,"abstract":"<p><p>Friedreich ataxia (FRDA) is an autosomal recessive disorder caused by GAA expansions in the FXN gene, which codes for the protein frataxin (FXN). These mutations reduce FXN expression, leading to mitochondrial dysfunction and multisystemic disease. Accumulating evidence suggests that neuronal dysfunction, rather than neuronal death, may drive the neurological phenotypes of FRDA, but the mechanisms underlying such neurological phenotypes remain unclear. To investigate the neural circuit basis of this dysfunction, we employed field recordings to measure Purkinje cell (PC) function and synaptic properties along with western blotting and immunohistochemistry to determine their density and structure in two established FRDA mouse models, the shRNA-frataxin (FRDAkd) and the frataxin knock in-knockout (KIKO) mice. Western blotting demonstrated subtle changes in mitochondrial proteins and only a modest reduction in the density of calbindin positive cells PCs in the cerebellar cortex of the FRDAkd mice, with no change in the density of PCs in the KIKO mice. Though PC density differed slightly in the two models, field recordings of parallel fiber-PC synapses in the molecular layer demonstrated concordant hypo-excitability of basal synaptic transmission and impairments of long-term plasticity using induction protocols associated with both potentiation and depression of synaptic strength. These results indicate that synaptic instability might be a common feature in FRDA mouse models.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"42"},"PeriodicalIF":2.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Spinocerebellar Ataxia 25: First Case Report of a Brazilian Family.","authors":"Renata Barreto Tenorio, José Sávio Soares de Lira, Marcela Ferreira Cordellini, Karina Carvalho Donis","doi":"10.1007/s12311-025-01794-2","DOIUrl":"10.1007/s12311-025-01794-2","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 25 (SCA25) is a rare autosomal dominant disorder caused by heterozygous pathogenic variants in the PNPT1 gene, primarily affecting the critical S1 RNA-binding domain. This study reports the first Brazilian and South American family with SCA25. To describe the clinical, genetic, and molecular findings in a family with a novel PNPT1 variant and compare them with previously reported cases. Clinical evaluation, neuroimaging, and genetic testing were performed on affected family members. The proband underwent clinical exome sequencing, with Sanger confirmation of the identified variant. Computational tools, including SpliceAI, were used to predict the molecular consequences of the variant. The proband, a 1-year-8-month-old girl, presented with progressive ataxia, cerebellar atrophy, and sensory neuropathy. Genetic testing identified a novel heterozygous truncating variant in PNPT1 (c.2068del; p.?), inherited from her father, who was mildly affected with polyneuropathy but no ataxia. SpliceAI predicted significant splicing disruptions, including intron retention or exon skipping, leading to a frameshift (p.(Arg690Glyfs*5)) and likely triggering nonsense-mediated decay or post-translational degradation. These findings align with previously reported PNPT1 variants associated with SCA25, which exhibit phenotypic variability and incomplete penetrance. This report expands the clinical and genetic spectrum of SCA25 and highlights the importance of considering this condition in the differential diagnosis of progressive ataxias. Further studies, including RNA and protein analyses, are required to confirm the molecular consequences of the PNPT1:c.2068del variant and to advance our understanding of the pathophysiology of SCA25.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":"24 2","pages":"41"},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081955","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}