Abstract
Objective: To examine the possible contribution of inflammation and breakdown of the blood–brain barrier in the central nervous system (CNS) of physiologically aged rats showing cognitive decline.
Methods: Young (3- to 6-month-old) and aged (24- to 30-month-old) Wistar rats were assessed by the novel object recognition test. Vascular and inflammatory changes in the CNS were investigated in whole-mount preparations or sections of retinas from young adult or aged male Wistar rats.
Results: Aged rats showed a significant impairment in short-term memory compared with young adults. Deterioration of blood–retinal barrier function in aged rats was evidenced by leakage of intravascular tracer into the retinal parenchyma and reduced immunoreactivity for the tight junctional protein, occludin. Immunohistochemistry revealed the presence of major histocompatibility complex (MHC) class II-positive resident microglia, activated T cells, and monocyte-like cells in the retinal parenchyma of aged rats only. Microglia positive for the ED1 antigen, indicative of phagocytic activity, were also observed in these retinas.
Conclusion: Breakdown of the blood–retinal barrier, MHC class II expression, microglial activation, and trafficking of activated T cells are associated with physiological aging. Such changes in the CNS may contribute to the pathogenesis of age-related cognitive decline.
This work was supported by grants to T. Chan-Ling from the National Health and Medical Research Council of Australia 464859 & 402824, Macular Vision Loss Support Society of Australia Inc, the Baxter Charitable Foundation, and the Rebecca Cooper Medical Research Foundation (Sydney, Australia). We thank A. Goodchild for blood pressure measurements; F. Seow and A. Broe (Concord Hospital, Sydney, Australia) for allowing us access to aged rats; C. Chamberlain and A. Everitt for helpful discussions; and R-A. Sterling, C. Jeffrey, and R. Smith for assistance with digital imaging and photography.
Ping Hu's current address is Prince of Wales Medical Research Institute, Sydney, Australia.