The receptor tyrosine kinase TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), are critically important for growth, survival and activity-dependent synaptic strengthening in the central nervous system. These TrkB-mediated actions occur in a highly cell-type specific manner. Here we report that cerebellar Purkinje cells, which are richly endowed with TrkB receptors, develop a normal morphology in trkB-deficient mice. Thus, in contrast to other types of neurons, Purkinje cells do not need TrkB for dendritic growth and spine formation. Instead, we find a moderate delay in the maturation of GABAergic synapses and, more importantly, an abnormal multiple climbing fiber innervation in Purkinje cells in trkB-deficient mice. Thus, our results demonstrate an involvement of TrkB receptors in synapse elimination and reveal a new role for receptor tyrosine kinases in the brain.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303929 | PMC |
http://dx.doi.org/10.1007/s11068-006-9002-z | DOI Listing |
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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!