The effect of NAD-299 and TCB-2 on learning and memory and hippocampal BDNF levels in Streptozotocin-induced Alzheimer s disease in male rats

Background and Aim : Alzheimer s disease (AD) is the most common form of dementia characterized by a progressive decline in cognitive function. The serotonergic system via 5-HT1A receptor and 5-HT2A receptor are proposed to affects cognitive process. In the present study, the effects of NAD-299 (5-HT1A receptor antagonist) and TCB-2 (5-HT2A receptor agonist) on learning and memory processes and hippocampal brain-derived neurotrophic factor (BDNF) levels have been investigated in streptozotocin-induced Alzheimer s disease in rats.Methods : Adult male Wistar rats (250–300 g) were divided into six groups: control, sham-operated, AD, AD+NAD-299 (icv for 30 days), AD+TCB-2 (icv for 30 days) and AD+NAD-299+TCB-2 [icv for 30 days). Following the treatment period, rats were subjected to behavioral tests of learning and memory. Then Hippocampal BDNF and amyloid-beta (Aβ) plaque were determined by ELISA Kit and Congo red staining, respectively.Results : Our results showed that icv-STZ injection decreased the discrimination index in the novel object recognition (NOR) test. In the passive avoidance (PAL) task, icv-STZ injection significantly decreased step-through latency (STLr) and increased time in dark compartment (TDC). Treatment with NAD-299, TCB-2, and NAD-299+TCB-2 attenuated the STZ-induced memory impairment in both NOR and PAL tasks. Icv-STZ induced a decrease in hippocampal BDNF level fallowing by Aβ plaques production in the brain, whereas treatment with NAD-299, TCB-2 and NAD-299+TCB-2 reduced Aβ plaques in the brain and increased the hippocampal BDNF level.Conclusion : These findings suggest that 5-HT1AR blockade by NAD-299 and 5-HT2AR activation by TCB-2 improve cognitive dysfunction in a rat model of AD and these drugs could potentially prevent the progression of AD.

کلیدواژه ها:

Alzheimer’s disease ، Streptozotocin ، 5-HT1A ، 5-HT2A ، Amyloid plaque ، cognition