Photoperiodic regulation of cerebral blood flow in white-footed mice (Peromyscus leucopus)

Abstract

Individuals living outside the tropics need to adjust their behavioral and physiological repertoires throughout the year to adapt to the changing seasons. White-footed mice (Peromyscus leucopus) reduce hippocampal volumes, hippocampal-dependent memory function, long-term potentiation, and alter neurogenesis in response to short (winter-like) day lengths (photoperiods). During winter, these mice putatively shunt energy away from the brain to maximize peripheral thermogenesis, immune function, and survival. We hypothesized that these changes in brain function are accompanied by alterations in brain vasculature. We maintained white-footed mice in short (8 h light/16 h dark) or long (16 h light/8 h dark) photoperiods for 8-9 weeks. Mice were then perfused with fluorescein isothiocyanate (FITC)-conjugated tomato (Lycopersicon esculentum) lectin to visualize the perfused cerebrovasculature. Short-day mice reduced hippocampal and cortical capillary density (FITC+area); vessels isolated from short day-exposed mice expressed higher mRNA levels of the gelatinase matrix metalloproteinase 2 (MMP2). Additionally, short-day mice reduced cerebral blood flow ~15[%] compared with their long-day counterparts, as assessed by laser speckle flowmetry. Immunohistochemistry revealed higher levels of MMP2 in the hippocampus of mice maintained in short days compared with long days, potentially contributing to the observed vascular remodeling. These data demonstrate that a discrete environmental signal (i.e., day length) can substantially alter cerebral blood flow in adult mammals.