Effects of Stress and MDMA on Hippocampal Gene Expression
| Autor: | Gary A. Gudelsky, Bethann N. Johnson, Bryan K. Yamamoto, Georg F. Weber |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Protein Folding
Serotonin Article Subject lcsh:Medicine Neuropeptide Hippocampus Pharmacology Serotonergic General Biochemistry Genetics and Molecular Biology Stress Disorders Post-Traumatic Serotonin Agents Downregulation and upregulation mental disorders medicine Animals Chronic stress 3 4-Methylenedioxyamphetamine General Immunology and Microbiology business.industry lcsh:R Neurotoxicity MDMA General Medicine medicine.disease Rats Gene Expression Regulation Protein Biosynthesis Unfolded protein binding Neurotoxicity Syndromes business psychological phenomena and processes Research Article medicine.drug |
| Zdroj: | BioMed Research International, Vol 2014 (2014) BioMed Research International |
| ISSN: | 2314-6133 |
| DOI: | 10.1155/2014/141396 |
| Popis: | MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature. |
| Databáze: | OpenAIRE |
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