Exaggerated astrocyte reactivity after nigrostriatal deafferentation in the aged rat

Abstract

Although clinical experience suggests that brain injury in the aged is associated with a poor prognosis, little research has examined this phenomenon at a cellular or molecular level. Unilateral 6-hydroxydopamine lesions of the nigrostriatal system were produced in 6-, 15- or 24-month-old rats. In the deafferented neostriatum, the time-dependent induction of glial fibrillary acidic protein (GFAP) was larger and persisted longer in the aged rats. The response of middle-aged rats was intermediate. In contrast, no induction of S-100 or glutamine synthetase was observed in any age group. In a second series of rats with stab wounds in the neostriatum, there were substantially larger GFAP inductions than after deafferentation, but fewer effects of age. However, in both lesion paradigms, GFAP staining increased in the contralateral striatum of old rats, but not in young rats. These data support and extend our earlier work describing larger GFAP RNA inductions after fornix transections in aged mouse hippocampus. The consistency of this exaggerated glial reactivity in the aged brain after modest injury suggests the following: 1) aged astrocytes are more sensitive to gliotrophic factors released by terminal degeneration, 2) larger quantities of such factors are produced after injury, 3) clearance of these factors is delayed in old rodents, and/or 4) aged astrocytes are less able to terminate GFAP inductions after activation. Given the potential role of inflammatory reactions as pathogenic mechanisms in Alzheimer's dementia, these data suggest that age-related glial hypersensitivity may independently increase the risk for some degenerative diseases.

Accelerated Glial Reactivity to Stroke in Aged Rats Correlates with Reduced Functional Recovery

“…Generally there is an increased astrocytic reaction following injury to the aging CNS. For example, Gordon et al (1997) found that nigrostriatal deafferentation causes a time-dependent induction of GFAP that is larger and more persistent in aged rats than in young animals. Interestingly, the authors noted an intensification of GFAP staining in the contralateral hemisphere of aged (but not young) rats, a phenomenon that was confirmed by our findings.…”

Baicalin mitigates cognitive impairment and protects neurons from microglia‐mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF‐κB signaling pathway

“…Immunohistochemistry was performed as previously described. 22 Briefly, paraffin-embedded slices (4 μm) were quenched to inactivate endogenous peroxidase for 30 minutes using 0.5% H 2 O 2 ; then, the nonspecific binding sites were blocked using 5% BSA (bovine serum albumin) at room temperature for 1 hour. The sections were incubated overnight at 4°C with Cleaved-caspase-3 (CASP3) antibody Immunofluorescence microscopy was performed on brain and cell slices as previously described.…”

Biochemical and Histochemical Evidence of Nonspecific Binding of α7nAChR Antibodies to Mouse Brain Tissue

“…Immunohistochemical analysis of ␣ 7 nAChRs was performed using 25-m free-floating sections spaced 300 m apart through the hippocampus. Details of this procedure were originally described elsewhere (Gordon et al 1997). All steps were performed on a rotating platform at ‫ف‬ 40 rpm, room temperature, unless otherwise stated.…”