Homiack Damek, O'Cinneide Emma, Hajmurad Sema, Dohanich Gary P, Schrader Laura A
a Neuroscience Program, Brain Institute , Tulane University , New Orleans , LA , USA.
b Department of Cell and Molecular Biology , Tulane University , New Orleans , LA , USA.
Stress. 2018 Jul;21(4):292-303. doi: 10.1080/10253890.2018.1484099. Epub 2018 Jun 19.
Post-traumatic stress disorder (PTSD) is characterized by the development of paradoxical memory disturbances including intrusive memories and amnesia for specific details of the traumatic experience. Despite evidence that women are at higher risk to develop PTSD, most animal research has focused on the processes by which male rodents develop adaptive fear memory. As such, the mechanisms contributing to sex differences in the development of PTSD-like memory disturbances are poorly understood. In this investigation, we exposed adult male and female Wistar rats to the synthetic alarm odor 2,4,5-trimethylthiazole (TMT) to assess development of generalized fear behavior and rapid modulation of glutamate uptake and signaling cascades associated with hippocampus-dependent long-term memory. We report that female Wistar rats exposed to alarm odor exhibit context discrimination impairments relative to TMT-exposed male rats, suggesting the intriguing possibility that females are at greater risk in developing generalized fear memories. Mechanistically, alarm odor exposure rapidly modulated signaling cascades consistent with activation of the CREB shut-off cascade in the male, but not the female hippocampus. Moreover, TMT exposure dampened glutamate uptake and affected expression of the glutamate transporter, GLT-1 in the hippocampus. Taken together, these results provide evidence for rapid sex-dependent modulation of CREB signaling in the hippocampus by alarm odor exposure which may contribute to the development of generalized fear.
创伤后应激障碍（PTSD）的特征是出现矛盾性记忆障碍，包括侵入性记忆和对创伤经历特定细节的失忆。尽管有证据表明女性患PTSD的风险更高，但大多数动物研究都集中在雄性啮齿动物形成适应性恐惧记忆的过程上。因此，导致PTSD样记忆障碍发展中性别差异的机制尚不清楚。在这项研究中，我们将成年雄性和雌性Wistar大鼠暴露于合成警报气味2,4,5-三甲基噻唑（TMT）中，以评估广泛性恐惧行为的发展以及与海马依赖性长期记忆相关的谷氨酸摄取和信号级联的快速调节。我们报告说，与暴露于TMT的雄性大鼠相比，暴露于警报气味的雌性Wistar大鼠表现出情境辨别障碍，这表明雌性在形成广泛性恐惧记忆方面面临更大风险这一有趣的可能性。从机制上讲，警报气味暴露迅速调节了与雄性而非雌性海马中CREB关闭级联激活一致的信号级联。此外，TMT暴露抑制了谷氨酸摄取并影响了海马中谷氨酸转运体GLT-1的表达。综上所述，这些结果为警报气味暴露对海马中CREB信号的快速性别依赖性调节提供了证据，这可能有助于广泛性恐惧的发展。
