Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female <i>Tsc2</i><sup>+/−</sup> Mice: The Importance of Including Both Sexes in Neuroscience Research
Manuel F. López-Aranda,
Karen Bach,
Raymond Bui,
Miranda Phan,
Odilia Lu,
Chirag Thadani,
Alessandro Luchetti,
Rochelle Mandanas,
Isaiah Herrera,
María Dolores López-Ávalos,
Alcino J. Silva
Affiliations
Manuel F. López-Aranda
Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29010 Málaga, Spain
Karen Bach
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
Raymond Bui
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
Miranda Phan
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
Odilia Lu
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
Chirag Thadani
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
Alessandro Luchetti
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
Rochelle Mandanas
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
Isaiah Herrera
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
María Dolores López-Ávalos
Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29010 Málaga, Spain
Alcino J. Silva
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
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.
