Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent neurons following partial monoamine loss induced by methamphetamine.

Abstract

The immediate-early gene Arc (activity-regulated cytoskeleton-associated protein) is provocative in the context of neuroplasticity because of its experience-dependent regulation and mRNA transport to and translation at activated synapses. Normal rats have more preproenkephalin-negative (ppe-neg; presumed striatonigral) neurons with cytoplasmic Arc mRNA than ppe-positive (ppe-pos; striatopallidal) neurons, despite equivalent numbers of these neurons showing novelty-induced transcriptional activation of Arc. Furthermore, rats with partial monoamine loss induced by methamphetamine (METH) show impaired Arc mRNA expression in both ppe-neg and ppe-pos neurons relative to normal animals following response-reversal learning. In this study, Arc expression induced by exposure to a novel environment was used to assess transcriptional activation and cytoplasmic localization of Arc mRNA in striatal efferent neuron subpopulations subsequent to METH-induced neurotoxicity. Partial monoamine depletion significantly altered Arc expression. Specifically, basal Arc expression was elevated, but novelty-induced transcriptional activation was abolished. Without novelty-induced Arc transcription, METH-pre-treated rats also had fewer neurons with cytoplasmic Arc mRNA expression, with the effect being greater for ppe-neg neurons. Thus, METH-induced neurotoxicity substantially alters striatal efferent neuron function at the level of Arc transcription, suggesting a long-term shift in basal ganglia neuroplasticity processes subsequent to METH-induced neurotoxicity. Such changes potentially underlie striatally based learning deficits associated with METH-induced neurotoxicity.

• Authors: Melissa L Barker-Haliski, Katharina Oldenburger, Kristen A Keefe
• Journal: Journal of neurochemistry (J Neurochem) Vol. 123 Issue 5 Pg. 845-55 (Dec 2012) ISSN: 1471-4159 [Electronic] England
• PMID: 22978492 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Chemical References

• Central Nervous System Stimulants
• Cytoskeletal Proteins
• Nerve Tissue Proteins
• RNA, Messenger
• activity regulated cytoskeletal-associated protein
• Methamphetamine
• Dopamine

Topics

• Animals
• Central Nervous System Stimulants (toxicity)
• Corpus Striatum (drug effects, metabolism)
• Cytoskeletal Proteins (biosynthesis)
• Dopamine (metabolism)
• Gene Expression Regulation
• In Situ Hybridization, Fluorescence
• Male
• Methamphetamine (toxicity)
• Nerve Tissue Proteins (biosynthesis)
• Neurons, Efferent (drug effects, metabolism)
• Neurotoxicity Syndromes (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Transcription, Genetic (drug effects)