This study provides a detailed anatomical description of the relation between olivo-cortico-nuclear modules of the intermediate cerebellum of the rat and the intrinsic zebrin pattern of the Purkinje cells. Strips of climbing fibers were labeled using small injections of biotinylated dextran amine into either the medial or dorsal accessory olives, while, in some cases, simultaneous retrograde labeling of Purkinje cells was obtained using gold-lectin injections into selected parts of the interposed nuclei. Our data are represented in a new, highly detailed, cortical surface reconstruction of the zebrin pattern and in relation to the collateral labeling of the climbing fibers to the cerebellar nuclei. We show that the somatotopic regions of the dorsal accessory olive behave differently in their projections to essentially zebrin-negative regions that represent the C1 and C3 zones of the anterior and posterior parts of the cortex. The rostral part of the medial accessory olive projects to zebrin-positive areas, in particular to the P4+ band of the anterior lobe and lobule VI and to the P5+ band of the posterior lobe, indicating that C2 has two noncontiguous representations in the SL and crus 1. By relating the areas of overlap that resulted from the injections in the accessory olives, i.e., labeling of climbing fiber strips and patches of climbing fiber nuclear collaterals, with the results from the injections in the interposed nuclei, i.e., retrograde labeling of Purkinje cells and of inferior olivary neurons, direct verification of the concept of modular cerebellar connections was obtained.
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PLoS 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.
View Article and Find Full Text PDFVet Res Commun
January 2025
Department of Veterinary Medicine, University of Perugia, Via San Costanzo, 4, Perugia, 06126, Italy.
This study describes the congenital goiter in an alpaca (Vicugna pacos) fetus aborted in November 2021 with the clinical and pathological findings in the dam that was found dead on the farm three weeks after a miscarriage. The dam was a black coat alpaca bred in the Netherlands, imported in Italy in January 2021, and housed in a farm of central Italy for breeding purposes. Signalment and clinical data on dam and fetus were collected from the farmer and referring veterinarian.
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