Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number.

Autor: Smith CJ; Duke University, Department of Psychology and Neuroscience, Durham, NC, USA., Kingsbury MA; Lurie Center for Autism, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Dziabis JE; Duke University, Department of Psychology and Neuroscience, Durham, NC, USA., Hanamsagar R; Duke University, Department of Psychology and Neuroscience, Durham, NC, USA., Malacon KE; Duke University, Department of Psychology and Neuroscience, Durham, NC, USA., Tran JN; Lurie Center for Autism, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Norris HA; Lurie Center for Autism, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Gulino M; Lurie Center for Autism, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Bordt EA; Lurie Center for Autism, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA., Bilbo SD; Duke University, Department of Psychology and Neuroscience, Durham, NC, USA. Electronic address: Staci.bilbo@duke.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2020 Nov; Vol. 90, pp. 332-345. Date of Electronic Publication: 2020 Aug 26.
DOI: 10.1016/j.bbi.2020.08.013
Abstrakt: Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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