Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine.

Yasaman Razavi,Mehdi Mehdizadeh,Ronak Shabani,Fariborz Keyhanfar,Abbas Haghparast

doi:10.1007/s11011-021-00774-9

Abstract

Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine whether cannabidiol (CBD) can promote proliferation and maturation of neuronal progenitor cells, this study investigated the CBD effect on neurogenesis in the hippocampal dentate gyrus (DG) following chronic exposure to meth in rats. The rats received 2mg/kg of meth twice a day for ten days. Next, immunofluorescence was performed to evaluate the effect of intracerebroventricular (ICV) administration of CBD (50μg/5 μL) over an abstinence period (ten days) on the expression levels of neurogenesis markers, such as Ki67, NeuN, and doublecortin (DCX). Moreover, neuronal degeneration in the hippocampus was assessed using Nissl staining. According to our findings, repeated ICV administration of CBD improved cell proliferation and neurogenesis and increased the number of Ki-67 and DCX-positive cells in the abstinence period. Meanwhile, meth treatment subjects caused a significant decrease in the number of neurogenesis makers, as compared to the control group. The neurogenesis markers (Ki-67 and DCX) could be somewhat reversed, while NeuN did not show any significant increase in the CBD group. Our findings demonstrated that CBD can induce neuroprotective effects by modulating neurogenesis. Therefore, it can provide a promising therapeutic approach to improve cognitive performance following chronic exposure to psychostimulant drugs, including meth.

Highlights

Adult neurogenesis is a distinguished example of activity-dependent neuroplasticity
Since the ICV administration of CBD (50 μg/5 μL) could prevent impairments in memory recognition among rats with chronic exposure to meth during the abstinence period (Razavi et al 2020b), we aimed to determine whether CBD affected the expression of hippocampal neurogenesis markers, namely Ki67, NeuN, and DCX, which indicated the amount of neuronal proliferation and differentiation in the dentate gyrus (DG)
Our findings indicated that repeated ICV administration of CBD at a dose of 50 μg/5 μL led to higher cell proliferation (i.e., Ki-67 immunoreactivity) and increased the number of neurons (i.e., DCX immunoreactivity) in the hippocampal DG during an abstinence period in rats with chronic meth exposure

Summary

Introduction

Adult neurogenesis is a distinguished example of activity-dependent neuroplasticity. It is influenced by numerous factors, including stress, drugs, and brain damage (Jun et al, 2012; Parent 2003; Van Praag et al, 1999). The properties of neural progenitor cells detected in the sub-granular zone (SGZ) are shown by adult hippocampal neurogenesis of the dentate gyrus (DG). After proliferation and migration of these cells to the granular zone (GZ), they are distinguished from mature granule neurons (Kempermann, 2008). Different neurogenesis phases can be identified using specific markers, and proliferation of progenitor cells is evaluated by Ki-67 (Gerdes et al, 1984). Clinical studies have shown that methamphetamine (meth) dependence alters the hippocampal morphology (Canales 2010a; Kim et al 2010)

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