Effects of Corticotropin-Releasing Factor 1 Receptor Antagonism on In Vivo Dentate Gyrus Long-Term Potentiation in the TgF344-AD Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by irreversible neurobiological deterioration and cognitive impairment. AD patients exhibit stress system abnormalities including upregulation of the corticotropin releasing factor type 1 receptor (CRF1) and elevated cortisol. Psychological distress increases the likelihood of AD diagnosis and hastens neurocognitive decline. Administration of the CRF1 antagonist, Antalarmin, reduces AD pathogenesis and anxiety-like behavior in models of AD. Motivated by these observations, the current study examined the potential contributions of CRF1 to altered synaptic plasticity in AD neuropathology and stress in the TgF344-AD rat model. In vivo electrophysiological recordings to assess long-term potentiation (LTP) in the perforant pathway to dentate gyrus synapses were performed in aged transgenic rats and wild-type (WT) controls (2-2.5 years). TgF344-AD rats had abnormal LTP measures of field excitatory post-synaptic potentials (fEPSP) and population spikes (PS). Treatment with Antalarmin did not alter LTP measures in TgF344-AD or WT rats. These observations indicate that LTP in TgF344-AD rats is reduced compared to WT rats and that acute treatment with a CRF1 antagonist did not rescue LTP deficits. Future research should further examine the mechanism of CRF1 in AD and implications of agonism or direct infusions of Antalarmin in vivo.