Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood

Abstract

Neurogenesis is known to take place in the adult brain. This work identifies T lymphocytes and microglia as being important to the maintenance of hippocampal neurogenesis and spatial learning abilities in adulthood. Hippocampal neurogenesis induced by an enriched environment was associated with the recruitment of T cells and the activation of microglia. In immune-deficient mice, hippocampal neurogenesis was markedly impaired and could not be enhanced by environmental enrichment, but was restored and boosted by T cells recognizing a specific CNS antigen. CNS-specific T cells were also found to be required for spatial learning and memory and for the expression of brain-derived neurotrophic factor in the dentate gyrus, implying that a common immune-associated mechanism underlies different aspects of hippocampal plasticity and cell renewal in the adult brain.

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

“…In addition, IGF-1 overexpression promotes neurogenesis and synaptogenesis in the dentate gyrus and IGF-1 knock out mouse exhibit a reduction in granule cell numbers (Beck et al, 1995;O'Kusky et al, 2000). Furthermore, Ziv et al (2006) reported that environmental enrichment-induced neurogenesis in the hilus correlates with hilar microglial activation and IGF-1 expression. Finally, in cell culture assays, the effects of IGF-1 on hippocampal progenitor cell proliferation were shown to be mediated, in part, via the MAPK pathway (Aberg et al, 2003).…”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…From a therapeutic standpoint, urging T cells to traffic to the brain via administration of a CNS-related antigen has been shown to exhibit both an antianxiety and antidepressant effect depending on the animal model (Lewitus and Schwartz, 2009;. Along similar lines, T cells have been shown to be essential for normal cognitive function such that T cell-deficient animals exhibit impaired learning and memory as revealed by Morris water maze, Barnes maze, and radial arm maze that can be reversed by the adoptive transfer of T cells (Kipnis et al, 2004;Ziv et al, 2006). Moreover, experiments using RAG-1 knockout mice (that are deficient in mature B and T cells) have revealed that long-term deficiencies in CD4+ T cells are associated with impaired behavioral responses including increased digging and marble-burying activities compared with wild-type mice (Rattazzi et al, 2013).…”

Behavioral immunization: immunity to self-antigens contributes to psychological stress resilience

“…6,12,13 In addition to the role of CNSspecific T cells in CNS repair, our group has found that adaptive immune cells are key players in CNS maintenance under nonpathological conditions, especially in hippocampal plasticity. 9,14 We showed that autoreactive T cells are needed to support hippocampal-dependent learning and memory tasks, as well as for the regulation of adult hippocampal neurogenesis and neurotrophic factor production, 14 possibly by regulating microglial phenotype. 15 Adaptive immunity in coping with mental stress Recently, we found an association between T cells and adaptation to psychological stress.…”