Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Department of Pharmacology and Therapeutics, Afe Babalola University, Ado-Ekiti, Nigeria.
Adv Neurobiol. 2024;37:457-495. doi: 10.1007/978-3-031-55529-9_26.
This chapter will focus on microglial involvement in neurodevelopmental and neuropsychiatric disorders, particularly autism spectrum disorder (ASD), schizophrenia and major depressive disorder (MDD). We will describe the neuroimmune risk factors that contribute to the etiopathology of these disorders across the lifespan, including both in early life and adulthood. Microglia, being the resident immune cells of the central nervous system, could play a key role in triggering and determining the outcome of these disorders. This chapter will review preclinical and clinical findings where microglial morphology and function were examined in the contexts of ASD, schizophrenia and MDD. Clinical evidence points out to altered microglial morphology and reactivity, as well as increased expression of pro-inflammatory cytokines, supporting the idea that microglial abnormalities are involved in these disorders. Indeed, animal models for these disorders found altered microglial morphology and homeostatic functions which resulted in behaviours related to these disorders. Additionally, as microglia have emerged as promising therapeutic targets, we will also address in this chapter therapies involving microglial mechanisms for the treatment of neurodevelopmental and neuropsychiatric disorders.
这一章将重点关注小胶质细胞在神经发育和神经精神疾病中的作用,特别是自闭症谱系障碍(ASD)、精神分裂症和重度抑郁症(MDD)。我们将描述神经免疫风险因素,这些因素在整个生命周期中导致这些疾病的发病机制,包括生命早期和成年期。小胶质细胞作为中枢神经系统的固有免疫细胞,可能在触发和决定这些疾病的结果方面发挥关键作用。这一章将回顾小胶质细胞形态和功能在 ASD、精神分裂症和 MDD 背景下的临床前和临床研究结果。临床证据表明小胶质细胞形态和反应性改变,以及促炎细胞因子表达增加,支持小胶质细胞异常参与这些疾病的观点。事实上,这些疾病的动物模型发现小胶质细胞形态和稳态功能改变,导致与这些疾病相关的行为。此外,由于小胶质细胞已成为有前途的治疗靶点,我们还将在这一章中讨论涉及小胶质细胞机制的治疗方法,以治疗神经发育和神经精神疾病。