Cholinergic regulation of striatal Nova mRNAs

• Published in: Neuroscience 2010-08, Vol.169 (2), p.619-627
• Main Authors: Jelen, N, Ule, J, Živin, M
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); alternative splicing; Animals; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Excitatory Amino Acid Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; kainate; Kainic Acid - pharmacology; Lithium Chloride - pharmacology; Male; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neuro-Oncological Ventral Antigen; Neurology; Nova; pilocarpine; Pilocarpine - pharmacology; Rats; Rats, Wistar; RNA, Messenger - metabolism; RNA-Binding Proteins - biosynthesis; RNA-Binding Proteins - genetics; Scopolamine - pharmacology; seizures; Seizures - metabolism; striatum; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.05.013

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.