Complex Neuroimmune Involvement in Neurodevelopment: A Mini-Review

Figures & data

Table 1 A Summary of Neurophysiological Functions and Neuroinflammatory Activities of Microglia and Astrocytes in Relation to Neurodevelopmental Diseases and Health

References	Finding	Non-Inflammatory Activity	Inflammatory Activity	Outcome	Association with Neurodevelopmental Diseases or Health
Han et al, 2021^Citation17	Astrocyte-derived cytokine expression regulates microglia homeostasis and microglial synaptic pruning	Yes		Neural circuit refinement	Normal brain development
Vainchtein et al, 2018^Citation30	Astrocytes regulate microglial metabolism to contribute to synaptic pruning	Yes		Proper neural circuitry formation	Normal brain development
Liu et al, 2019^Citation58	Astrocytes can influence microglial activation and production of inflammatory cytokines		Yes	Microglial activation	The pathogenesis of affective disorders
Sokolowski et al, 2014^Citation87	Microglial elimination of neurons undergoing apoptosis is guided by “find-me” signals	Yes		Elimination of excessive neurons	Normal brain development
Diaz-Aparicio et al, 2020;^Citation89 Parkhurst et al, 2013^Citation101	Microglia promotes neurogenesis by secreting factors such as BDNF	Yes		Increased neuron production	Normal brain development
Parellada et al, 2021^Citation90	Microglia is a driver of excessive dendritic pruning and dendritic apoptosis		Yes	Imbalance of excitatory/inhibitory circuit activity	Schizophrenia
Schafer et al, 2012;^Citation91 Hong et al, 2016;^Citation92 Scott-Hewitt et al, 2020;^Citation93 Lehrman et al, 2018^Citation94	Microglial synaptic pruning is guided by “eat-me” signals	Yes		Neural circuit refinement	Normal brain development
Zhan et al, 2014^Citation97	A reduction of microglia during the early postnatal period results in a synaptic pruning deficit		Yes	Impaired functional brain connectivity and deficits in social interaction	Deficits in social interaction is a common manifestation of many neurodevelopmental diseases
Weinhard et al, 2018^Citation98	Microglia remodels synapses by interfering with pre- and post-synaptic connections	Yes		Synaptic circuit remodeling and maturation	Normal brain development
Aarum et al, 2003^Citation102	Microglia can direct migration and differentiation of neural precursor cells	Yes		Directing the replacement of damaged or lost cells in the CNS during neurodevelopment	Normal brain development
Lebovitz et al, 2019^Citation103	Microglial dysfunction leads to impaired synaptic remodeling	Yes		Social deficits due to dysfunction of microglia	Autism spectrum disorders
Todd et al, 2019^Citation105	Microglia can provide protection to neurons	Yes		Neuronal survival	Normal brain development
Aronica et al, 2012^Citation106	Astrocytes regulate the innate immune responses in epilepsy		Yes	Astrocyte-mediated neuronal damage	Epileptogenesis/epilepsy
Hart et al, 2021^Citation107	Astrocytes modulate homeostatic functions and neuroinflammation	Yes	Yes	Neuroinflammation initiation and resolving neuroinflammation	CNS injury and repair mechanisms
Christopherson et al, 2005^Citation109	Astrocytes contribute to synaptogenesis	Yes		Efficient synaptogenesis and neural circuitry formation	Normal brain development
Chung et al, 2013^Citation114	Astrocytes help mediate synapse elimination	Yes		Proper neural circuitry formation	Normal brain development
Li et al, 2022^Citation123	Impairment of astrocyte-derived ATP is an etiological factor for neurodevelopmental disorders		Yes	Autism spectrum disorder-like behavior	Neurodevelopmental diseases
Gravina et al, 2022^Citation126	Impairment of astrocyte-mediated synaptic pruning		Yes	Excessive phagocytic activity in the brain	Schizophrenia
Wang et al, 2022^Citation136	Astrocytes contribute to intellectual disability via the inflammatory response		Yes	CNS homeostasis disruption and inhibition of neuronal growth	Intellectual disability

Figure 1 Schematic diagram showing neuroimmune activities involved in neurodevelopment. Microglia and astrocytes play a role in appropriate neurodevelopment and contribute to the pathophysiology of neurodevelopmental diseases. In frank inflammation, which is stimulated by perinatal immune activation, astrocytes and microglia are activated by immune stimulus. This activation leads to production of proinflammatory cytokines (TNFa, IL-1β) and damage to the blood–brain barrier. Infiltration of immune cells to the brain parenchyma together with astrocyte and microglial activation results in neuronal damage. Under physiological conditions, astrocytes and microglia play critical roles during neurodevelopment and homeostasis. Astrocyte- and microglia-driven cytokines regulate 5 critical processes of neurodevelopment that are crucial for developing a healthy brain: neuronal proliferation, synaptogenesis, synaptic pruning, neuronal migration, and neural circuitry regulation. Created with BioRender.com.

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