Evolutionary Perspective on Microglial/Neuronal Coupling with Special Relevance to Psychiatric Illnesses

Abstract

Journal of Psychiatry AbstractMicroglia have selectively evolved as a morphologically and chemically distinct class of immuno-competent CNS resident cells with potent bidirectional signaling capabilities linked to induction of a macrophage-like phenotype following metabolic, microbiological, or viral insults. It has been empirically determined that a conserved set of shared chemical messengers connects a communication network mediating reciprocal exchange of regulatory information between immune, central nervous, and neuroendocrine systems. From an evolutionary perspective, the pluripotent neuro-protective capabilities of invertebrate microglia have been extended and amplified in classes of mammalian microglia. The state-dependent plasticity of microglia has provoked considerable empirical investigation into their functional/regulatory roles in mediating innate immune surveillance and neural protection within the CNS. Upon pathophysiological dysregulation, aberrant microglial activities may provide significant contributory factors in the etiology and persistence of major neurological, degenerative, and psychiatric disorders. Within this context, invertebrate microglia appear to represent highly appropriate model systems to investigate underlying cellular and molecular mechanisms involved in higher order neuroimmune regulation of multiple CNS activities by mammalian microglia.

New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

“…Microglial cells with migratory activity have also been described in snails and insects (Sonetti et al, 1994). Thus, the open circulatory system of invertebrates lent itself to the origin of neuroimmune cooperative events, whereby macrophage-like immune cells gained the capabilities for penetration and residence within "privileged" neuronal compartments (Stefano and Krearn, 2015).…”

“…Both IL-1β and monoamines are produced in response to neural trauma and circulating IL-1β and norepinephrine exert multiple effects on different cells and organs in the body, including the vasculature, inflammatory cells and neurons. Many of these shared signalling mechanisms are functionally linked with diverse forms of injury or neuronal death in mammals or the development of neurodegenerative-and psychiatric diseases in humans (Elenkov et al, 2000;Allan et al, 2005;Denes et al, 2011;Mélik Parsadaniantz et al, 2015;Stefano and Krearn, 2015). Some of these signalling pathways, have been observed in invertebrates and vertebrates during 500 million years of evolution, such as iNOS (Peruzzi et al, 2004), anandamide (Stefano et al, 1996) or 17β-estradiol (Stefano et al, 2003).…”

Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders

“…Accordingly, the predominant focus of the multi-generation pharmacopeia of clinically employed therapeutic agents for AfSD-related psychiatric disorders involves functional targeting of dysregulated DA-ergic and interactive biogenic amine signaling systems in cortical and limbic CNS areas (Moonen et al 2017 ). Several of these classes of therapeutic agents have been observed to partially restore pathophysiological changes in mitochondrial bioenergetics associated with AfSD in discrete CNS areas (Stefano and Kream 2015a , b ). In contrast, there is a significant lack of empirical studies designed to evaluate the effects of commonly used antidepressant and neuroleptic agents on AfSD-associated gut dysbiosis (Macedo et al 2017 ).…”