Department of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada.
Neurosci Biobehav Rev. 2021 Dec;131:135-163. doi: 10.1016/j.neubiorev.2021.09.018. Epub 2021 Sep 16.
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.
从心理社会到神经源性/损伤到全身/微生物等压力源都可能影响小胶质细胞的炎症过程，但对于它们对小胶质细胞营养特性的影响知之甚少。最近的研究确实表明，小胶质细胞可以调节神经元可塑性，可能通过脑源性神经营养因子 (BDNF)。鉴于 BDNF 与神经精神和神经退行性病理学之间的联系，这一点尤为重要。我们假设小胶质细胞的某些激活状态在维持 BDNF 释放到神经元突触的微妙平衡中发挥作用。本重点综述将讨论不同的“激活剂”如何影响小胶质细胞 BDNF 的表达和释放，并探讨小胶质细胞上原肌球蛋白受体激酶 B (TrkB)表达的问题。然后，我们将评估基于性别的小胶质细胞功能和 BDNF 表达的差异，以及小胶质细胞如何参与应激反应和相关疾病，如抑郁症。我们将借鉴来自各种其他疾病的研究，强调调节剂的挑战和机遇，这些调节剂可以将小胶质细胞转变为具有“营养”表型的细胞，以期为与应激源相关的疾病提供潜在的治疗方法。
