Original articleNeuronal subset-specific phosphatase and tensin homolog knockout mice exhibit age and brain region-associated alterations in microglia/macrophage activationNarvaiz, David A.a; Sullens, D. Gregorya; Santana-Coelho, Daniellea; Lugo, Joaquin N.a,b,c Author Information aDepartment of Psychology and Neuroscience bDepartments of Biology cInstitute of Biomedical Studies, Baylor University, Waco, Texas, USA Received 2 May 2022 Accepted 31 May 2022 Correspondence to Joaquin N. Lugo, PhD, Department of Psychology and Neuroscience, Baylor University, One Bear Place # 97334, Waco, TX 76798, USA, Tel: +254 710 2389; fax: +254 710 3033; e-mail: [email protected] NeuroReport ():10.1097/WNR.0000000000001808, July 05, 2022. | DOI: 10.1097/WNR.0000000000001808 Buy PAP Metrics Abstract Seizures induce brain region-dependent enhancements in microglia/macrophage activation. Neuronal subset–specific phosphatase and tensin homolog (PTEN) knockout (KO) mice display hyperactive mammalian target of rapamycin (mTOR) signaling in the hippocampus, cerebellum, and cortex followed by seizures that increase in severity with age. To determine if KO mice also exhibit alterations in the spatiotemporal activation pattern of microglia, we used flow cytometry to compare the percentage of major histocompatibility complex-II activated microglia/macrophages between KO and wildtype (WT) mice at 5, 10, and 15 weeks of age. At 5 weeks, microglia/macrophage activation was greater in the cortex, P < 0.001, cerebellum, P < 0.001, and hippocampus, P < 0.001, of KO compared to WT mice. At 10 weeks, activation was greatest in the cortex of KO mice, P < 0.001, in the cerebellum of WT mice, P < 0.001, but similar in the hippocampus, P > 0.05. By 15 weeks, activation in the hippocampus was more than 25 times greater in KO mice compared to WT mice, P < 0.001. We show that hyperactive mTOR signaling is associated with an altered spatiotemporal pattern of microglia/macrophage activation in the brain and induces an enhanced neuroimmune response in the hippocampus. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.