Nitric Oxide Critically Regulates Purkinje Neuron Dendritic Development Through a Metabotropic Glutamate Receptor Type 1–Mediated Mechanism
| Autor: | Matthew J.E. Maksoud, Vasiliki Tellios, Yun-Yan Xiang, Wei-Yang Lu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
Agonist Cerebellum Dendritic spine medicine.drug_class Neurogenesis Nitric Oxide Synthase Type I Neurotransmission Nitric Oxide Receptors Metabotropic Glutamate 050105 experimental psychology Nitric oxide Mice Purkinje Cells 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals 0501 psychology and cognitive sciences Mice Knockout 05 social sciences Dendrites Cell biology Mice Inbred C57BL medicine.anatomical_structure nervous system Neurology chemistry Metabotropic glutamate receptor Excitatory postsynaptic potential Metabotropic glutamate receptor 1 Neurology (clinical) 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Cerebellum. 19:510-526 |
| ISSN: | 1473-4230 1473-4222 |
| Popis: | Nitric oxide (NO), specifically derived from neuronal nitric oxide synthase (nNOS), is a well-established regulator of synaptic transmission in Purkinje neurons (PNs), governing fundamental processes such as motor learning and coordination. Previous phenotypic analyses showed similar cerebellar structures between neuronal nitric oxide null (nNOS−/−) and wild-type (WT) adult male mice, despite prominent ataxic behavior within nNOS−/− mice. However, a study has yet to characterize PN molecular structure and their excitatory inputs during development in nNOS−/− mice. This study is the first to explore morphological abnormalities within the cerebellum of nNOS−/− mice, using immunohistochemistry and immunoblotting. This study sought to examine PN dendritic morphology and the expression of metabotropic glutamate receptor type 1 (mGluR1), vesicular glutamate transporter type 1 and 2 (vGluT1 and vGluT2), stromal interaction molecule 1 (STIM1), and calpain-1 within PNs of WT and nNOS−/− mice at postnatal day 7 (PD7), 2 weeks (2W), and 7 weeks (7W) of age. Results showed a decrease in PN dendritic branching at PD7 in nNOS−/− cerebella, while aberrant dendritic spine formation was noted in adult ages. Total protein expression of mGluR1 was decreased in nNOS−/− cerebella across development, while vGluT2, STIM1, and calpain-1 were significantly increased. Ex vivo treatment of WT slices with NOS inhibitor L-NAME increased calpain-1 expression, whereas treating nNOS−/− cerebellar slices with NO donor NOC-18 decreased calpain-1. Moreover, mGluR1 agonist DHPG increased calpain-1 in WT, but not in nNOS−/− slices. Together, these results indicate a novel role for nNOS/NO signaling in PN development, particularly by regulating an mGluR1-initiated calcium signaling mechanism. |
| Databáze: | OpenAIRE |
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