Protective effects of 5-HT 1A receptor antagonist and 5-HT 2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer's disease

Simin Afshar, Siamak Shahidi, Ali Haeri Rohani, Sara Soleimani Asl, Alireza Komaki
Journal of Chemical Neuroanatomy 2019 January 23, 96: 140-147
Alzheimer's disease (AD) is a neurodegenerative disorder and neuropathologically characterized by the aggregation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, enhanced oxidative stress and neurodegeneration. Involvement of serotonergic systems in AD has been supposed and it is suggested that serotonin receptors modulation may provide a novel therapeutic target for AD. This study aimed at investigating the protective effect of NAD-299 (the selective 5-HT1A receptor antagonist) and TCB-2 (the potent5-HT2A receptor agonist) on the hippocampal oxidative stress biomarkers and the number of intact neurons in streptozotocin (STZ)-induced Alzheimer's disease in rats. Fifty adult male Wistar rats weighing 250-300 g were divided into five groups: sham, STZ-treated, STZ + NAD-299 (5 μg/1 μl icv), STZ + TCB-2 (5 μg/1 μl icv) and STZ + NAD-299 (5 μg/0.5 μl icv) +TCB-2 (5 μg/0.5 μl icv). At the end of the study, the rats were weighed, then hippocampal oxidative stress markers [total antioxidant capacity (TAC), malondialdehyde (MDA), the total thiol group (TTG), and DNA damage] were measured. In addition, the number of intact neurons in the CA1 area of the hippocampus was determined using hematoxylin and eosin staining. The results showed that icv injection of STZ reduced hippocampal TAC, TTG levels and intact pyramidal cells and increased DNA damage and MDA levels in the hippocampus of STZ-treated rats. Icv administration of NAD-299, TCB-2, and NAD-299+TCB-2 increased TAC and TTG contents and hippocampal intact neurons and reduced hippocampal DNA damage, MDA levels in icv-STZ treated rats. Moreover, there was no significant difference in weight changes among the experimental groups. According to the obtained results, it is suggested that 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) can reduce oxidative stress and neuronal loss in a rat model of AD and may prevent the AD progression.

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