Cited by 10RNA Research and SplicingEpilepsy research and treatmentNeuroscience and Neuropharmacology Research

Cholinergic regulation of striatal Nova mRNAs

Jelen, N., Ule, J., Živin, M.·2010·Neuroscience

Abstract

Alternative splicing is an important mechanism for expanding proteome diversity from a limited number of genes, especially in higher vertebrates. Brain-specific splicing factors play an important role in establishing specific patterns of alternative splicing in the brain and thereby contribute to its complex architecture and function. Nova proteins are splicing factors that are expressed specifically in the central nervous system, where they regulate a large number of pre-mRNAs encoding synaptic proteins that are important for the balance of neuronal excitation and inhibition. Since this balance is interrupted in epileptic seizures, we explored whether LiCl/pilocarpine- or kainate-induced epileptic seizures would induce changes in the levels of Nova mRNAs in the rat brain. We found that the muscarinic agonist, pilocarpine, but not the glutamatergic agonist, kainate, induced a significant downregulation of Nova2 mRNA and upregulation of all three Nova1 mRNA isoforms in the striatum. Treatment with the muscarinic antagonist, scopolamine, at the onset of pilocarpine-induced seizures inhibited the seizures and the changes in Nova mRNA levels. Therefore it seems likely that pilocarpine stimulation of muscarinic acetylcholine receptors was a prerequisite for the observed changes, while the contribution of other striatal neurotransmitter systems activated by seizures could not be excluded. We propose that the LiCl/pilocarpine seizure model could serve as a valuable tool for studying mechanisms of Nova-regulated alternative splicing in rat striatum.

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Crossref · 10.1016/j.neuroscience.2010.05.013

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  • In our dataset, several genes carrying HHMCs and associated with basal ganglia functions stand out, like SLITRK1 and NOVA1.

    “in our dataset, several genes carrying HHMCs and associated with basal ganglia functions (critical for language and cognition) stand out, like SLITRK1114 and NOVA136,115–118 (Supplementary Information 4).”

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Authors
Jelen, N., Ule, J., & Živin, M.
Affiliations
  • University of Ljubljana (SI)
  • MRC Laboratory of Molecular Biology (GB)
Corresponding author
Živin, M.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2010-08
Volume
169
Issue
2
Pages
619-627
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2055727344
Cited by
10
References
39
Citations by year
2026: 1 · 2025: 2 · 2020: 1 · 2019: 1 · 2014: 1 · 2012: 1
FWCI
0.52
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Wellcome Trust (089701)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
alternative splicing, striatum, cholinergic modulation, muscarinic receptors, pilocarpine-induced seizures, kainate-induced seizures, scopolamine, epilepsy, excitation-inhibition balance
MeSH terms
Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Corpus Striatum, Kainic Acid, Male, Nerve Tissue Proteins, Pilocarpine, RNA, Messenger, Scopolamine, Seizures, RNA-Binding Proteins, Rats, Wistar, Lithium Chloride, Excitatory Amino Acid Agonists, Muscarinic Agonists, Muscarinic Antagonists, Rats

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