Overexpression of catalase targeted to mitochondria improves neurovascular coupling responses in aged mice

AbstractMoment-to-moment adjustment of cerebral blood flow (CBF) to neuronal activity via the homeostatic mechanism known as neurovascular coupling (NVC) has an essential role in maintenance of normal brain function. In advanced age cerebromicrovascular endothelial dysfunction impairs NVC responses, which contribute to age-related cognitive decline. Recently, we have shown that pharmacological treatments that attenuate mitochondrial production of reactive oxygen species (ROS) provide significant neurovascular protection, improving NVC responses in aged mice. Transgenic mice that overexpress human catalase localized to the mitochondria (mCAT) are protected from age-related mitochondrial oxidative stress and exhibit a longevity phenotype associated with resistance to several age-related pathologies. The present study was designed to test the hypothesis that mitochondria-targeted overexpression of catalase also confers protection against age-related impairment of NVC responses. To achieve this goal, NVC responses were assessed in aged (24 months old) mCAT mice and compared with those in age-matched wild-type mice and young control mice by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that mitochondrial overexpression of catalase resulted in improved NVC in aged mice due to preserved NO-mediated (L-NAME inhibitable) component of the response. Thus, our present and previous findings demonstrate that interventions tha...

Source: AGE - October 22, 2019 Category: Geriatrics Source Type: research