PERICYTE AND CAPILLARY MAY DECLINE DEPENDING ON THE AGING PROCESS IN MICE

Purpose. In this study, we explore the effects of aging on pericytes and capillaries using mice. Pericytes are important components of the neurovascular unit and function as contractile cells around the walls of capillaries. They play many important roles in the brain, such as blood vessel formation, cerebral brain blood flow, maintenance of the blood-brain barrier, and regulation of immune cell entry into the CNS. Dysfunction of pericytes contribute to a wide range of illnesses that result in cognitive impairments such as cerebrovascular disease, stroke, Alzheimer's disease (AD), and other neurological disorders. Aging has been studied and shown to be an established risk for vascular dysfunction that affects the integrity of the neurovascular unit. Furthermore, studies have shown significant reductions in pericyte density during age-related disorders, but these studies are few. Most nutrients in the brain are supplied by capillaries, and because pericytes are embedded on capillaries, studying their patterns and effects may lead to a better understanding of the pathophysiology and preliminary triggers of age-related disorders. In this study, we explore whether both pericyte and capillary numbers are affected in the adult brain of mice as they age. Methods. All experiments were performed on young (3 month old; n=3) and old (20-23 month old; n=3) C57BL/6 male mice. To identify pericytes and capillaries for quantification, immunohistochemistry and immunofluorescence were used. Pericytes were stained using the biomarker PDGFrβ and capillaries were stained using Lectin. CA1, CA2, CA3, and DG sites were chosen for quantification in the hippocampus, and layers I-VI in the somatosensory cortex of each mouse. Confocal imaging was used to study and quantify the population of PDGFrβ and lectin-positive cells. T-tests were performed to compare the number of pericytes in the hippocampus and somatosensory cortex of the two groups of mice (young and old). Results. Old mice exhibited significantly lower capillary (via lectin) and pericyte (via PDGFrβ) numbers than young mice (p < 0.0001) in the hippocampus. There was no significant reduction in the number of pericyte (p = 0.1448) and capillary (p = 0.0967) in the somatosensory cortex. Pericytes that expressed PDGFrβ were only classified as such when colocalized to capillaries. To record the number of pericytes embedded on capillaries, the number of PDGFrβ + Lectin that expressed a "bump-on-a-log" morphology was also quantified and showed a significant reduction in the hippocampus (p < 0.0001) and somatosensory cortex (p = 0.0110) with age. Conclusion. Since cerebrovascular dysfunction plays a vital role in the development of cognitive impairment disorders, understanding the aging patterns of neurovasculature cells such as pericytes may aid in the early prevention of age-related illnesses.