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 (LTP), 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 (16:8) photoperiods for 8-9 wks. 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 MMP2. Additionally, short day mice reduced cerebral blood flow ∼15% compared to their long day counterparts as assessed by laser speckle flowmetry. Immunohistochemistry revealed higher levels of MMP2 protein in the hippocampus of mice maintained in short- compared to 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 an adult mammal.
Significance Statement Individuals living in non-tropical climates show seasonal changes in physiology and behavior primarily controlled by day length (photoperiod). Specifically, white-footed mice (Peromyscus leucopus) display reduced hippocampal function, neurogenesis, and cognitive capacity in response to short days. It is unknown, however, whether these changes are preceded or accompanied by alterations in cerebral blood flow. This study provides evidence that short days elicit a reduction in hippocampal and cortical blood flow, and this reduction is accompanied by increased mRNA and protein expression of the gelatinase MMP2, a primary component in vascular remodeling. These results have broad implications for our understanding of postnatal brain plasticity, environmental modulation of behavior, and seasonal changes in brain function.
Authors report no conflict of interest.
This research was supported by NSF IOS 11-18792 to RJN, Presidential and Pelotonia fellowships to JCB, and in part by AHA 12SDG11780023 to CR.