Involvement of CNS luteinizing hormone receptor in Alzheimer's disease pathogenesis.

Abstract

CNS Luteinizing hormone and its receptor have been shown to modulate neuronal plasticity and cognition. Importantly, levels of brain LH are inversely related to levels in the periphery, thus low upon menopause-related upregulation of peripheral LH. Previously we have shown that downregulation of peripheral LH improves function and plasticity in AD mouse models, improvements that are positively correlated with brain LH. However, whether these improvements are driven directly through the activation of central LHR signaling is not known. Therefore, the current study addresses whether central LHR activation was able to rescue cognitive and neuronal plasticity changes previously observed by peripheral LH downregulation. Female APP/PS1 transgenic and wild-type mice underwent ovariectomy or sham surgery and received ICV hCG or aCSF treatment for 8 weeks. Upon completion cognitive testing, tissue was collected to determine changes in structural plasticity and Abeta pathology. Preliminary data demonstrates the ability of hCG treatment to differentially modulate cognition, pathology, and plasticity markers. This work supports the involvement of LHR in CNS function and begets its further study as a contributor linking menopause and increased AD risk.