Altered antigen expression of microglia in the aged rodent CNS

Abstract

Microglia, the resident macrophages of the central nervous system, are characterised by a highly specialized morphology and unusual antigenic phenotype. Microglia appear to be downregulated by their microenvironment when compared to other tissue macrophages. We have studied the microglia in brains of healthy, aged rats with a panel of monoclonal antibodies. We have found that microglia in the brains of these aged rats express antigens that are downregulated or absent from microglia of juvenile rats. The stimuli which give rise to this upregulated phenotype are not known. Age related changes in the phenotype of microglia should be taken into account when considering the possible role of microglia in neuropathological conditions.

[11C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

“…Aging is known to lead to changes in the microglial phenotype with a shift toward a more activated state; the microglia tend to become larger and more complex, with several changes in antigen expression. 18,[35][36][37] Arterial blood sampling in rodents is technically challenging, and its requirement is not ideal for longitudinal investigations. The use of arterial blood data can also lead to additional variance in the outcome measures, seen here as a higher standard deviation in group-wise estimates and lower repeatability (ICC) for V T as compared with blood-free measures (the SUV).…”

Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats

“…9 -THC, 9 -tetrahydrocannabinol; aCSF, artificial cerebral spinal fluid; AD, Alzheimer's disease; CB1, cannabinoid receptor 1; CB2, cannabinoid receptor 2; CBr, cannabinoid receptors; DG, dentate gyrus; EC, entorhinal cortex; LPS, lipopolysaccharide; NMDA, N-methyld-aspartate; PBS, phosphate buffer saline; TBS, Tris buffer saline; WIN-55212-2, (R)-(+)- [2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) and treatment with NSAIDs does not reduce microglia activation in old rats, in contrast to their effectiveness in young rats (Hauss-Wegrzyniak et al, 1999), thus raising the possibility of microglial senescence (Perry et al, 1993;Streit, 2006).…”

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

“…A chronic inflammatory response, identified by increases in ED1 + activated microglia, has been demonstrated repeatedly in the CNS of young animals months after irradiation (8,10,13,14). To date, however, experimental studies of radiation-induced inflammation, brain injury and cognitive dysfunction have been conducted almost exclusively in animals a few weeks to a few months old, young ages that do not reflect important neurobiological changes that occur with normal aging, such as decreased proliferation and neurogenesis (15)(16)(17)(18), increased microglial activation (19,20) and expression of pro-inflammatory cytokines (20)(21)(22). Experimental studies of stroke, traumatic brain injury, exogenous cytokine administration, and axotomy support the hypothesis that aging impacts the intensity and duration of brain inflammation and glial activation following challenges (23)(24)(25)(26)(27)(28).…”