Serotonin-related gene expression in female monkeys with individual sensitivity to stress.

TitleSerotonin-related gene expression in female monkeys with individual sensitivity to stress.
Publication TypeJournal Article
Year of Publication2005
AuthorsBethea CL, Streicher JM, Mirkes SJ, Sanchez RL, Reddy AP, Cameron JL
Date Published2005
KeywordsAmenorrhea, Animals, Brain Chemistry, Cell Count, Disease Models, Animal, Down-Regulation, Female, Gene Expression, Genetic Predisposition to Disease, Macaca fascicularis, Membrane Glycoproteins, Membrane Transport Proteins, Menstrual Cycle, Molecular Sequence Data, Monoamine Oxidase, Nerve Tissue Proteins, Progesterone, Promoter Regions, Genetic, Raphe Nuclei, Receptor, Serotonin, 5-HT1A, RNA, Messenger, Sequence Homology, Nucleic Acid, Serotonin, Serotonin Plasma Membrane Transport Proteins, Stress, Psychological

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n=3; normal menstrual cyclicity through two stress cycles), medium stress resistant (n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n=4; anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (P<0.04). SERT mRNA OD in the caudal DRN was positively correlated with serum progesterone during a pre-stress control cycle (P<0.0007). 5HT1A mRNA OD signal tended to decline in the stress-sensitive group, but statistical difference between averages was lacking in analysis of variance. However, 5HT1A mRNA signal was positively correlated with control cycle progesterone (P<0.009). There was significantly less MAO-A mRNA signal in the stress-sensitive group (P<0.007) and MAO-A OD was positively correlated with progesterone from a pre-stress control cycle (P<0.007). MAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (P<0.003). There were significantly fewer serotonin neurons in the stress-sensitive group. All animals contained only the long form of the 5HTTLPR. Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present.

Alternate JournalNeuroscience
PubMed ID15780474
Grant ListMH50748 / MH / NIMH NIH HHS / United States
MH62677 / MH / NIMH NIH HHS / United States
RR000163 / RR / NCRR NIH HHS / United States
U54 HD 18185 / HD / NICHD NIH HHS / United States
Faculty Member Reference: 
John M. Streicher, PhD