Protective Effects of 5-HT1A Receptor Inhibition and 5-HT2A Receptor Stimulation Against Streptozotocin-Induced Apoptosis in the Hippocampus.

Siamak Shahidi,Alireza Komaki,Sara Soleimani Asl,Nasrin Hashemi-Firouzi,Simin Afshar

doi:10.21315/mjms2019.26.2.5

Abstract

IntroductionIntracerebroventricular administration of streptozotocin (icv-STZ) induced apoptosis changes in neurons similar to Alzheimer’s disease. The serotonergic system via its receptor involved in survival of neurons. The present study examined the ability of selective 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) to attenuate the apoptosis caused by the icv-STZ in the rat.MethodsThe icv-STZ (3 mg/kg, 10 μL, twice) induced neuronal loss in the hippocampus of adult male rats. Animals were divided into naive control, sham-operated, STZ+saline (1 μL, icv), STZ+NAD-299 (5 μg/μL, icv), STZ+TCB-2 (5 μg/μL, icv), and STZ+NAD-299+TCB-2 (5 μg/μL of any agent, icv) groups. Following the 35 days’ treatment period, neuronal apoptosis was detected using the Tunnel. Cells with morphological features of apoptotic cell were contended by microscopy.ResultsTCB-2 and NAD-299 administration decreased number of apoptotic neurons in the treatment group compared with the STZ group. Combined treatment of STZ rat with NAD+TCB more decreased number of apoptotic cells in compare to TCB-2 or NAD-299 treated STZ groups.ConclusionTreatment with 5-HT1A receptor antagonist or 5-HT2A receptor agonist diminished apoptosis. The beneficial effect of 5HT1A receptor inhibition was potentiated with activation of 5-HT2A receptor in prevention of apoptosis in hippocampus.

Highlights

Intracerebroventricular administration of streptozotocin induced apoptosis changes in neurons similar to Alzheimer's disease
NAD-299 and TCB-2 were dissolved in dimethyl sulfoxide (DMSO) and STZ was dissolved in normal saline
Tukey post-hoc analysis revealed a higher number of apoptotic neurons in the STZ group, than in the control, sham and STZ treated with NAD299, TCB-2 and NAD+TCB groups, respectively (P < 0.001)

Summary

Introduction

Intracerebroventricular administration of streptozotocin (icv-STZ) induced apoptosis changes in neurons similar to Alzheimer's disease. The present study examined the ability of selective 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) to attenuate the apoptosis caused by the icv-STZ in the rat. Alzheimer’s disease (AD) is a neurodegenerative disorder [1] that leads to progressive cognitive dysfunction [2,3,4] and affects different areas of the brain such as the amygdala, entorhinal cortex, and hippocampus [3, 5]. Accumulation of Aβ plaques in the hippocampus lead to synaptic degeneration [12,13,14], neuronal apoptosis [15] and cognitive impairment [16, 17].

Objectives

Methods

Results

Discussion

Conclusion