Cerebellum最新文献

Recognizing the MRI characteristics of progressive multifocal leukoencephalopathy is essential for early diagnosis. This report describes the oldest known case of an 83-year-old man with rapidly progressive dementia and HIV-associated classic PML. Brain MRI revealed hallmark findings, including asymmetric, continuous, non-enhancing subcortical lesions in the parietooccipital regions and the "shrimp sign" in the cerebellar white matter. These characteristic imaging patterns, in the appropriate clinical context, are clues for the early identification of PML.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and restricted and repetitive patterns of behavior. In addition, individuals diagnosed with ASD may also present cognitive impairments. The neurobiological mechanisms possibly associated with the cause of ASD have not yet been fully elucidated. Studies suggest that brain alterations, especially in the cerebellum, play a fundamental role in the etiology of ASD. This brain region, traditionally associated with motor control, has been implicated in several cognitive and emotional processes, many of which are impaired in autistic individuals. This mini-review examines the evidence on cerebellar abnormalities associated with ASD, discussing their implications for the understanding and treatment of the disorder.

In the cerebellar cortex, 17β-estradiol (E2) binds to estrogen receptors (ERs) and plays a role in regulating cerebellar synaptic plasticity and motor learning behaviors. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of E2 on synaptic transmission between cerebellar molecular layer interneurons (MLIs) and Purkinje cells (PCs) in urethane-anesthetized mice. Using in vivo cell-attached and whole-cell recordings combined with immunohistochemistry, we examined MLI-PC synaptic responses elicited by facial air-puff stimulation. Cell-attached recordings from PCs demonstrated that air-puff stimulation of the ipsilateral whisker pad elicited MLI-PC synaptic currents (P1), which were significantly enhanced by local micro-application of E2 to the cerebellar molecular layer. The E2-induced potentiation of P1 amplitude exhibited dose dependency, with a 50% effective concentration (EC50) of 30 nM. The effects of E2 on amplitude of P1 and pause of simple spike firing were completely prevented by blockade of ERs or ERβ, but not by blockade of ERα or a G-protein coupled receptor (GPER). Application of a selective ERβ agonist mimicked and overwhelmed the E2-induced enhancement of the MLI-PC synaptic transmission. Whole-cell recording with biocytin staining showing that E2 does not change the spontaneous and the evoked spike firing properties of basket-type MLIs. Rotarod test indicated that microinjection of E2 onto the cerebellar surface significantly promotes initial motor learning ability, which is abolished by blockade of ERβ. ERβ immunoreactivity was expressed in the ML and PC layer, especially around the PC somata in the mouse cerebellar cortex. These results indicate that E2 binds to ERβ, resulting in an enhance in the cerebellar MLI-PC synaptic transmission and an improvement of initial motor learning ability in vivo in mice.

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.

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.

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.

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.

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.

Background: 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.

Objective: 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.

Methods: A comprehensive literature review was conducted, focusing on the genetic advancements in diagnosing ILOCA.

Results: 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.

Conclusion: 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.

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.