The effects of the 5-HT7 receptor on hippocampal long-term potentiation and apoptosis in a rat model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder involving synaptic loss and impairments in learning and memory. Long-term potentiation (LTP) of synaptic function is a model of learning- and memory-related neural plasticity, of which serotonin (5-HT) is a key modulator in the hippocampus. As the 5-HT7 receptor subtype is implicated in hippocampal neuronal function, dendritic rearrangement, and neurogenesis, the aim of this study was to assess the effect of 5-HT7 receptor activation on hippocampal synaptic plasticity and apoptosis in a rat model of AD. AD was induced via intracerebroventricular (icv) administration of streptozotocin (STZ). Forty adult male Wistar rats were divided into naive control, sham-operated, AD+saline (1μL icv for 30days), and AD+AS19 (a selective 5-HT7 receptor agonist, 1μg/μL, icv for 30days) groups. Following the treatment period, rats were anesthetized and placed in a stereotaxic apparatus. LTP was induced by high-frequency stimulation of the perforant pathway. The population spike (PS) and field excitatory postsynaptic potentials (fEPSP) in the dentate gyrus of the hippocampus were measured. Then, neuronal apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The PS and fEPSP of the AD+saline group were significantly decreased compared to the control and sham-operated groups. Moreover, the PS and fEPSP of the AD+AS19 group were significantly increased compared to the AD+saline group. We found that STZ-induced AD impaired LTP in the dentate granule cells. One month of AS19 treatment restored hippocampal LTP and reduced neuronal apoptosis in the AD+AS19 group. These findings suggest that 5-HT7 receptor activation by AS19 improves synaptic dysfunction in a rat model of AD via reduction of apoptosis in the hippocampus and it could potentially prevent the progression of AD.

Keywords: Alzheimer’s disease; Hippocampus; Long-term potentiation; Rat; Serotonin-7 receptor; Streptozotocin.