1. The authors' goal was to compare the size and density of Purkinje cells in the cerebellum of subjects with and without autism. Blocks of cerebellum were dissected at autopsy from the brains of age, sex- and postmortem-intervaled (PMI) groups of autistic and normal control individuals (N = 5 per group). Frozen, unfixed blocks were sectioned and stained with 1% cresyl violet. 2. The linear, molecular, granular densities and cross-sectional area of Purkinje cells were measured using computer-assisted image analysis. The average cross-sectional areas of Purkinje cells of the patients with autism were smaller by 24% when compared to the normal subjects. Two of the five autistic subjects had mean Purkinje cell sizes that corresponded to greater than 50% reduction in size. There was a substantial effect size difference in Purkinje cell size (eta2 = 0.29) between control and autistic brains (F(1, 8) = 3.32, P = 0.106). No differences in Purkinje cell densities were observed between the two groups 3. These data indicate the possibility of Purkinje cell atrophy in autism with significant neurohistological heterogeneity among individuals diagnosed with this disorder.
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http://dx.doi.org/10.1023/a:1019861721160 | DOI Listing |
Nat Metab
January 2025
CECAD Excellence Center, University of Cologne, Cologne, Germany.
Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Neuroscience, Laboratory of Prion Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
There is no cure for Marinesco-Sjögren syndrome (MSS), a genetic multisystem disease linked to loss-of-function mutations in the SIL1 gene, encoding a BiP co-chaperone. Previously, we showed that the PERK kinase inhibitor GSK2606414 delays cerebellar Purkinje cell (PC) degeneration and the onset of ataxia in the woozy mouse model of MSS. However, GSK2606414 is toxic to the pancreas and does not completely rescue the woozy phenotype.
View Article and Find Full Text PDFJ Vis Exp
December 2024
The David and Inez Myers Laboratory for Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Faculty of Health and Medical Sciences, School of Medicine, Tel Aviv University;
Cerebellar Purkinje cells (PCs) exhibit a unique interplay of high metabolic rates, specific chromatin architecture, and extensive transcriptional activity, making them particularly vulnerable to DNA damage. This necessitates an efficient DNA damage response (DDR) to prevent cerebellar degeneration, often initiated by PC dysfunction or loss. A notable example is the genome instability syndrome, ataxia-telangiectasia (A-T), marked by progressive PC depletion and cerebellar deterioration.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Cerebro, Emoción y Conducta, School of Medicine, Universidad de las Américas (UDLA), Quito 170124, Ecuador.
Paraneoplastic cerebellar degeneration (PCD) is a rapidly progressive, immune-mediated syndrome characterized by the degeneration of Purkinje cells, often associated with the presence of antibodies targeting intracellular antigens within these cells. These autoantibodies are implicated in the induction of cytotoxicity, leading to Purkinje cell death, as demonstrated in in vitro models. However, the precise roles of antibodies and T lymphocytes in mediating neuronal injury remain a subject of ongoing research, with T cells appearing to be the main effectors of cerebellar injury.
View Article and Find Full Text PDFCurr Biol
January 2025
Johns Hopkins University, Department of Biomedical Engineering, 720 Rutland Avenue, Baltimore 21205, USA. Electronic address:
The integration of different sensory streams is required to dynamically estimate how our head and body are oriented and moving relative to gravity. This process is essential to continuously maintain stable postural control, autonomic regulation, and self-motion perception. The nodulus/uvula (NU) in the posterior cerebellar vermis is known to integrate canal and otolith vestibular input to signal angular and linear head motion in relation to gravity.
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