Mechanisms of Susceptibility and Resilience to PTSD: Role of Dopamine Metabolism and BDNF Expression in the Hippocampus

Abstract

Susceptibility and resilience to post-traumatic stress disorder (PTSD) are recognized, but their mechanisms are not understood. Here, the hexobarbital sleep test (HST) was used to elucidate mechanisms of PTSD resilience or susceptibility. A HST was performed in rats 30 days prior to further experimentation. Based on the HST, the rats were divided into groups: (1) fast metabolizers (FM; sleep duration < 15 min); (2) slow metabolizers (SM; sleep duration ≥ 15 min). Then the SM and FM groups were subdivided into stressed (10 days predator scent, 15 days rest) and unstressed subgroups. Among stressed animals, only SMs developed experimental PTSD, and had higher plasma corticosterone (CORT) than stressed FMs. Thus, resilience or susceptibility to PTSD was consistent with changes in glucocorticoid metabolism. Stressed SMs had a pronounced decrease in hippocampal dopamine associated with increased expressions of catecholamine-O-methyl-transferase and DA transporter. In stressed SMs, a decrease in monoaminoxidase (MAO) A was associated with increased expressions of hippocampal MAO-A and MAO-B. BDNF gene expression was increased in stressed FMs and decreased in stressed SMs. These results demonstrate relationships between the microsomal oxidation phenotype, CORT concentration, and anxiety, and they help further the understanding of the role of the liver–brain axis during PTSD.

Limited Cheese Intake Paradigm Replaces Patterns of Behavioral Disorders in Experimental PTSD: Focus on Resveratrol Supplementation

“…Interestingly, trans -resveratrol (RES), a natural polyphenol belonging to the phytoalexins similar to SSRIs, has been found to downregulate the mRNA expression of 5-HT transporter in the hippocampus [ 28 ]. Recent studies have shown that RES can alleviate anxiety-like behavior and decrease brain-derived neurotrophic factor (BDNF) levels, which are typically decreased in stressed rats in experimental PTSD models [ 29 , 30 ]. It is worth noting that PTSD-resilient rats exhibit increased hippocampal BDNF mRNA levels along with simultaneous increases in DOP (DAT) transporter mRNA levels in the hippocampus [ 30 ].…”

“…Recent studies have shown that RES can alleviate anxiety-like behavior and decrease brain-derived neurotrophic factor (BDNF) levels, which are typically decreased in stressed rats in experimental PTSD models [ 29 , 30 ]. It is worth noting that PTSD-resilient rats exhibit increased hippocampal BDNF mRNA levels along with simultaneous increases in DOP (DAT) transporter mRNA levels in the hippocampus [ 30 ].…”

Adaptation to intermittent hypoxia protects the brain in post-traumatic stress disorder

“…Наиболее известной, хорошо валидированной и приближенной к клинике экспериментальной моделью ПТСР является предаторный стресс (ПС) у грызунов [16]. Эта модель позволяет разделить животных на высоко-и низкотревожных для изучения возможных механизмов устойчивости к стрессу [17][18][19][20]. ПС моделируют путем экспозиции крыс к запаху кошачье мочи или виду кошки на 10-15 мин в день в течение 10 дней.…”

“…Эти параметры используются для расчета индекса тревожности, разработанного Cohen с соавт. [16] и широко используемого в моделях ПТСР [17][18][19][20][21].…”

“…BDNF защищает нейроны гиппокампа от повреждения и гибели и стимулирует их регенерацию [54]. Экспрессия BDNF выше у устойчивых к ПТСР крыс, чем у чувствительных, и, по-видимому, BDNF является важным фактором этой устойчивости [18]. Показано, что АГ увеличивает экспрессию BDNF и тормозит апоптоз в гиппокампе мышей [26].…”