RT Journal Article T1 Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female Tsc2+/− Mice: The Importance of Including Both Sexes in Neuroscience Research A1 López-Aranda, Manuel F. A1 Bach, Karen A1 Bui, Raymond A1 Phan, Miranda A1 Lu, Odilia A1 Thadani, Chirag A1 Luchetti, Alessandro A1 Mandanas, Rochelle A1 Herrera, Isaiah A1 López-Ávalos, María Dolores A1 Silva, Alcino J. K1 Inmunología K1 Niños recién nacidos - Desarrollo K1 Esclerosis tuberosa AB 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; Tsc2+/− 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 (Tsc2+/− mice), while no effect was observed in wild type (WT) mice. Moreover, we found that the same immune activation in Tsc2+/− 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 Tsc2+/− 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. PB MDPI YR 2024 FD 2024-01-17 LK https://hdl.handle.net/10630/45782 UL https://hdl.handle.net/10630/45782 LA eng NO López-Aranda MF, Bach K, Bui R, Phan M, Lu O, Thadani C, Luchetti A, Mandanas R, Herrera I, López-Ávalos MD, Silva AJ. Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female Tsc2+/- Mice: The Importance of Including Both Sexes in Neuroscience Research. Biomedicines. 2024 Jan 17;12(1):203. doi: 10.3390/biomedicines12010203. PMID: 38255309; PMCID: PMC10813674. NO Takeda Pharmaceutical Company Limited NO Human Frontier Science Program (Ref.#: LT000822/2011- L) NO Children’s Tumor Foundation (Grant#: 2014-01-014 NO NIH R01 MH084315 DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 18 mar 2026