Microglia in the aging brain: relevance to neurodegeneration

“By using in vivo two-photon imaging techniques, Nimmerjahn et al[37].”

“Extrinsic factors might include neurotransmitter, oxidative stress, neuroendocrine factors[10,68], hormones, and pathological factors such as abnormal protein aggregation [52] that exists in the microenvironment where microglia live.”

“When triggered by appropriate stimulation, microglia rapidly transformed from a resting state to an activated state with deramified shape and enhanced antigen presentation, which has been graded to a series of stages[18].”

“Microglia are distributed ubiquitously throughout the brain and function as resident macrophages and antigen-presenting cells in the CNS[35,36].”

“These studies indicate that microglia are capable of being both neurotrophic and neurotoxic, depending on the specific stimulus, the severity of injury, and the environment [31-34].”

“These genes include Abbinding scavenger receptors A (SRA), CD36, receptor for advanced glycosylation end products (RAGE), Abdegrading enzymes (insulysin, neprilysin) and MMP9 [74].”

“Insulin-like signaling pathway has been shown to regulate life span in worms, flies, and mice[ 72 ].”

“Microglia activation is normally controlled under physiological conditions of the CNS through neuron-glia contact, CD200R-CD200 pathway[19], neuronal electrical activity[20], and/or some soluble neurotransmitters [21].”

“”[50] Characteristics of “dystrophic” microglia that were observed in the aged brain include deramification (loss of finely branched cytoplasmic processes), cytoplasmic beading/spheroid formation, shortened and twisted cytoplasmic processes, and instances of partial or complete cytoplasmic fragmentation[50].”

“These parameters indicate that as humans and rodents age microglia take on a phenotype consistent with a pro-inflammatory response, even in the absence of overt pathological stimuli (Luo et al. 2010; Choi & Won, 2011; Wong, 2013; Sierra et al. 2014; Ojo et al. 2015; Barrientos et al. 2015a).”

“…aging changes in microglia have been hypothesized to drive the pathogenic progression through a diminution of neuroprotective functions, direct increases in neurotoxicity, and dysregulated responses to signals and perturbations (Flanary et al., 2007; Streit et al., 2008; Luo et al., 2010).”

“…hypothesized that changes in the aging microglia drive pathogenic progression of diseases or injury through a diminution of neuroprotective functions, increase in neurotoxicity, and dysregulation of responses to signals and perturbations (Flanary et al., 2007; Lopes et al., 2008; Luo et al., 2010).”