RT Journal Article
T1 Role of Type I Interferon Signaling and Microglia in the Abnormal Long-term Potentiation and Object Place Recognition Deficits of Male Mice With a Mutation of the Tuberous Sclerosis 2 Gene.
A1 López-Aranda, Manuel Francisco
A1 Boxx, Gayle M.
A1 Phan, Miranda
A1 Bach, Karen
A1 Mandanas, Rochelle
A1 Herrera, Isaiah
A1 Taloma, Sunrae
A1 Thadani, Chirag
A1 Lu, Odilia
A1 Bui, Raymond
A1 Liu, Shuhan
A1 Nan, Li
A1 Zhou, Yu
A1 Cheng, Genhong
A1 Silva, Alcino J.
K1 Interferón
K1 Microglia
K1 Neuroglia
K1 Memoria
K1 Hipocampo (Cerebro)
K1 Esclerosis tuberosa - Modelos animales
AB BACKGROUND: Tuberous sclerosis complex is a genetic disorder associated with high rates of intellectual disability and autism. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-) show deficits in hippocampal dependent tasks and abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of tuberous sclerosis complex, the results presented here demonstrate a role for microglia in these deficits. METHODS: To test the possible role of microglia and type I interferon in abnormal hippocampal-dependent memory and LTP of Tsc2+/- mice, we used field recordings in CA1 and the object place recognition (OPR) task. We used the colony stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia in Tsc2+/- mice and interferon alpha/beta receptor alpha chain null mutation (Ifnar1-/-) to manipulate a signaling pathway known to modulate microglia function.RESULTS: Unexpectedly, we demonstrate that male, but not female, Tsc2+/- mice show OPR deficits. These deficits can be rescued by depletion of microglia and by the Ifnar1-/- mutation. In addition to rescuing OPR deficits, depletion of microglia also reversed abnormal LTP of the Tsc2+/- mice. Altogether, our results suggest that altered IFNAR1 signaling in microglia causes the abnormal LTP and OPR deficits of male Tsc2+/- mice.CONCLUSIONS: Microglia and IFNAR1 signaling have a key role in the hippocampal-dependent memory deficits and abnormal hippocampal LTP of Tsc2+/- male mice.
PB Elsevier
YR 2023
FD 2023-07
LK https://hdl.handle.net/10630/39306
UL https://hdl.handle.net/10630/39306
LA eng
NO López-Aranda MF, Boxx GM, Phan M, et al. Role of Type I Interferon Signaling and Microglia in the Abnormal Long-term Potentiation and Object Place Recognition Deficits of Male Mice With a Mutation of the Tuberous Sclerosis 2 Gene. Biol Psychiatry Glob Open Sci. 2022;3(3):451-459. Published 2022 Apr 14. doi:10.1016/j.bpsgos.2022.03.015
NO This work was supported by the Human Frontier Science Program (Fellowship No. LT000822/2011-L [to MFL-A]), Children’s Tumor Foundation (Grant No. 2014-01-014 [to MFL-A]), Takeda Pharmaceutical Company Limited, and the National Institutes of Health (Grant No. R01 MH084315 [to AJS]).
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026