Cholinergic regulation of striatal Nova mRNAs
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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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).”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [115]
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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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