Apoaequorin differentially modulates fear memory in adult and aged rats

Abstract

Introduction: Cognitive deficits during aging are pervasive across species and learning paradigms. One of the major mechanisms thought to play a role in age-related memory decline is dysregulated calcium (Ca2+) homeostasis. Aging is associated with impaired function of several calcium-regulatory mechanisms, including calcium-binding proteins that normally support intracellular Ca2+ regulation. This age-related calcium-binding protein dysfunction and changes in expression lead to disrupted maintenance of intracellular Ca2+, thus contributing to memory decline. Other work has found that age-related cognitive deficits can be mitigated by either blocking Ca2+ entry into the cytosol or preventing its release from intracellular Ca2+ stores. However, the effect of calcium-binding protein administration on cognitive function during aging is not well-understood. Our laboratory has previously shown that the calcium-binding protein apoaequorin (AQ) is neuroprotective during oxygen–glucose deprivation, a model of in vitro ischemia characterized by calcium-induced excitotoxicity. The current experiments assessed the effect of direct dorsal hippocampal AQ infusion on trace and context fear memory in adult and aged rats. Methods: Adult (3–6 months) and aged (22–26 months) male F344 rats were randomly assigned to different experimental infusion groups before undergoing trace fear conditioning and testing. In experiment 1, rats received bilateral dorsal hippocampal infusions of either vehicle or AQ (4% w/v) 24 hr before trace fear conditioning. In experiment 2, rats received bilateral dorsal hippocampal infusions of either vehicle or 4% AQ 1 hr before trace fear conditioning and 1 hr before testing. Results: Aged rats displayed impaired trace and context fear memory. While a single AQ infusion 24 hr before trace fear conditioning was insufficient to rescue age-related trace fear memory deficits, AQ infusion 1 hr before both conditioning and testing abolished age-related context fear memory deficits. Conclusions: These results suggest that intrahippocampal infusion of AQ may reverse aging-related deficits in hippocampus-dependent context fear memory.