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Stressors ranging from psychogenic/social to neurogenic/injury to systemic/microbial can impact microglial inflammatory processes, but less is known regarding their effects on trophic properties of microglia. Recent studies do suggest that microglia can modulate neuronal plasticity, possibly through brain derived neurotrophic factor (BDNF). This is particularly important given the link between BDNF and neuropsychiatric and neurodegenerative pathology. We posit that certain activated states of microglia play a role in maintaining the delicate balance of BDNF release onto neuronal synapses. This focused review will address how different "activators" influence the expression and release of microglial BDNF and address the question of tropomyosin receptor kinase B (TrkB) expression on microglia. We will then assess sex-based differences in microglial function and BDNF expression, and how microglia are involved in the stress response and related disorders such as depression. Drawing on research from a variety of other disorders, we will highlight challenges and opportunities for modulators that can shift microglia to a "trophic" phenotype with a view to potential therapeutics relevant for stressor-related disorders., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been implicated in mood and anxiety disorders and is upregulated by antidepressants. It has marked effects on synaptic and extra-synaptic plasticity through tropomyosin receptor kinase B (TrkB). Importantly, early life stressors that affect BDNF production are known to predispose individuals towards the later development of depression or anxiety disorders. Yet, few studies have actually assessed the long-term impact of selective early life BDNF manipulation. Therefore, we utilized a knock-in transgenic mouse line (TrkB F616A ) with a mutation on the full-length TrkB receptor (TrkB.tk+), to reversibly block early postnatal BDNF/TrkB signaling. This was done during exposure to early life stress (maternal separation) followed by exposure to 35 days of chronic unpredictable stress (CUS) in adulthood. The TrkB.tk + mice that received the stressor treatments displayed a blunted anhedonic-like response (sucrose preference), compared to stressed animals that did not have the transient early life TrkB knockdown. But the TrkB.tk + mice actually showed an enhanced anxiety-like response in an open field in response following the CUS. This was paralleled by reductions of BDNF within the PFC and hippocampus of stressed TrkB.tk + mice, but basal elevations of BDNF was evident in the nucleus accumbens. These data are consistent with the contention that early in life, BDNF may program stress responsive circuits but this may differentially map onto depressive and anxiety-like responses in adulthood., (Copyright © 2019 Elsevier B.V. All rights reserved.)