Dystrophic microglia in the aging human brain

Abstract

We have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high-resolution LN-3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68-year-old) than in the younger one (38-year-old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age-related declines in cognitive function.

Glucocorticoid‐mediated modulation of morphological changes associated with aging in microglia

“…Further research should point out which other age‐related variables contribute to these morphological changes of microglia. Our work supports previous evidence describing dystrophic microglial in the aged brain (Streit, Sammons, Kuhns & Sparks, 2004), age‐related microglial changes in actin (dis)assembly genes that arrange the cell cytoskeleton (Galatro et al., 2017), and a decline in engagement of microglia with their environment in a brain‐region‐dependent manner (Grabert et al., 2016). Interfering with these processes by GC‐mediated modulation of neuroinflammation under (patho)physiological conditions might help to restore microglial homeostasis during aging and therefore possibly neuronal network maintenance as well as behavior (Bilbo & Schwarz, 2012).…”

β-Amyloid Stimulates Murine Postnatal and Adult Microglia Cultures in a Unique Manner

“…This is not surprising given the fact that microglia in aged human and rodent brains undergo morphologic dystrophy characterized by enlargement, deramification, and adoption of a more phagocytic phenotype (Sheng et al, 1998;Streit et al, 2004). More importantly, studies using both human and rodent adult microglial cultures have demonstrated that adult cells respond differently than postnatal cells regarding upregulation of cyclooxygenase expression (Hoozemans et al, 2002) and interleukin 6 (IL-6) and IL-1␤ secretion (Xie et al, 2003) after stimulation with A␤ (Hoozemans et al, 2002) and LPS (Xie et al, 2003).…”

“…This discrepancy suggests that the microglial response to A␤ derived from postnatal culture studies may differ significantly from that used by adult or aged microglia. In fact, in aged humans and rodents, it has been demonstrated that microglia undergo a morphologic dystrophy characterized by enlargement, deramification, and adoption of a more phagocytic phenotype (Sheng et al, 1998;Streit et al, 2004). These differences suggest that microglial cultures from aged brains may offer a more relevant model system for determining cellular responses to A␤ stimulation during disease.…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Brain aging includes proinflammatory phenotypes, altered signaling, and accumulation of senescent microglia (Harry, 2013; Mosher & Wyss‐Coray, 2014). Abnormalities in microglial cytoplasmic structure were observed in a case study of two nondemented subjects (one 68‐year‐old and one 38‐year‐old) were defined as microglial dystrophy which was further concluded as a sign of microglial cell senescence (Streit, Sammons, Kuhns, & Sparks, 2004). A transcriptional analysis of microglia from discrete brain regions at three different ages in mouse revealed that microglia aging could happen in a region‐specific manner (Grabert et al, 2016).…”