López-Aranda Manuel F, Bach Karen, Bui Raymond, Phan Miranda, Lu Odilia, Thadani Chirag, Luchetti Alessandro, Mandanas Rochelle, Herrera Isaiah, López-Ávalos María Dolores, Silva Alcino J
Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29010 Málaga, Spain.
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
Biomedicines. 2024 Jan 17;12(1):203. doi: 10.3390/biomedicines12010203.
There is evidence that viral infections during pre-natal development constitute a risk factor for neuropsychiatric disorders and lead to learning and memory deficits. However, little is known about why viral infections during early post-natal development have a different impact on learning and memory depending on the sex of the subject. We previously showed that early post-natal immune activation induces hippocampal-dependent social memory deficits in a male, but not in a female, mouse model of tuberous sclerosis complex (TSC; mice). Here, we explored the impact of a viral-like immune challenge in object memory. We demonstrate that early post-natal immune activation (during the first 2 weeks of life) leads to object memory deficits in female, but not male, mice that are heterozygous for a gene responsible for tuberous sclerosis complex ( mice), while no effect was observed in wild type (WT) mice. Moreover, we found that the same immune activation in adult mice was not able to cause object memory deficits in females, which suggests that the early post-natal development stage constitutes a critical window for the effects of immune challenge on adult memory. Also, our results suggest that mTOR plays a critical role in the observed deficit in object memory in female mice. These results, together with previous results published by our laboratory, showing sex-specific memory deficits due to early post-natal immune activation, reinforce the necessity of using both males and females for research studies. This is especially true for studies related to immune activation, since the higher levels of estrogens in females are known to affect inflammation and to provide neuroprotection.
有证据表明，产前发育期间的病毒感染是神经精神疾病的一个危险因素，并会导致学习和记忆缺陷。然而，对于产后早期发育期间的病毒感染为何会根据受试者的性别对学习和记忆产生不同影响，人们知之甚少。我们之前表明，在结节性硬化症（TSC；小鼠）的雄性而非雌性小鼠模型中，产后早期免疫激活会诱发海马体依赖的社会记忆缺陷。在此，我们探讨了类病毒免疫挑战对物体记忆的影响。我们证明，产后早期免疫激活（在出生后的前2周内）会导致患有结节性硬化症相关基因杂合的雌性而非雄性小鼠出现物体记忆缺陷（小鼠），而在野生型（WT）小鼠中未观察到影响。此外，我们发现成年小鼠中的相同免疫激活无法导致雌性小鼠出现物体记忆缺陷，这表明产后早期发育阶段是免疫挑战对成年记忆产生影响的关键窗口。而且，我们的结果表明，mTOR在雌性小鼠观察到的物体记忆缺陷中起关键作用。这些结果与我们实验室之前发表的结果一起，表明产后早期免疫激活导致的性别特异性记忆缺陷，强化了在研究中同时使用雄性和雌性的必要性。对于与免疫激活相关的研究尤其如此，因为已知雌性体内较高水平的雌激素会影响炎症并提供神经保护。
