Microglia as a Hub for Suicide Neuropathology: Future Investigation and Prevention Targets

Abstract

Suicide is a complex public health challenge associated worldwide with one death every 40 s. Research advances in the neuropathology of suicidal behaviors (SB) have defined discrete brain changes which may hold the key to suicide prevention. Physiological differences in microglia, the resident immune cells of the brain, are present in post-mortem tissue samples of individuals who died by suicide. Furthermore, microglia are mechanistically implicated in the outcomes of important risk factors for SB, including early-life adversity, stressful life events, and psychiatric disorders. SB risk factors result in inflammatory and oxidative stress activities which could converge to microglial synaptic remodeling affecting susceptibility or resistance to SB. To push further this perspective, in this Review we summarize current areas of opportunity that could untangle the functional participation of microglia in the context of suicide. Our discussion centers around microglial state diversity in respect to morphology, gene and protein expression, as well as function, depending on various factors, namely brain region, age, and sex.

Using focused ultrasound to modulate microglial structure and function

“…Microglia constantly adapt their morphology to probe and sense their environment ( Savage et al, 2019 ; Bosch and Kierdorf, 2022 ). On average, microglia extend and retract their processes at a rate of 1.5 μm per minute in mice ( Nimmerjahn et al, 2005 ; Fuhrmann et al, 2010 ) and can increase their cell body size to enhance translation and traduction, as well as phagocytic turnover ( Gonçalves de Andrade et al, 2022 ). The morphological states of microglia exist in a spectrum and are broadly classified as: ramified (normal soma, highly branched processes), ameboid (enlarged cell soma with filopodia), hypertrophic (large soma, short and thick processes), rod-shaped (small nuclei and bipolar processes), and dystrophic (fragmented) ( Savage et al, 2019 ; Šimončičová et al, 2022 ).…”

Ketogenic diet alters microglial morphology and changes the hippocampal lipidomic profile distinctively in stress susceptibleversusresistant male mice upon repeated social defeat

“…There were no changes in these microglial interactions between CTRL, SUS, and RES mice under both diets (Table 2). As microglia-synapse interactions are relevant to the regulation of neuronal activity and plasticity processes, notably upon stress and in MDD 93 , microglial direct contacts with excitatory synapses were next quantified. They were classified as contacts with presynaptic axon terminals (identified by their synaptic vesicles), dendritic spines (recognized by their postsynaptic density) and synaptic clefts (contact with both pre-and post-synaptic elements) (Fig.…”

Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice

“…Both glial cells contribute to neuroinflammation by producing a range of inflammatory mediators (i.e., cytokines, chemokines, growth factors, etc.) and consequent neuronal activation or sensitization in the central nervous system (CNS) [18,19]. Microgliosis and astrogliosis are nonspecific reactive changes manifested in their proliferation, hypertrophy or ramification with increased expression of the activation markers, ionized calcium-binding adapter molecule (Iba1) [20] and glial fibrillary acidic protein (GFAP), respectively [21,22].…”