Mohamed Nabil

Conference 2023 Live Talk

Talk title

Adipose tissue-derived mesenchymal stem cells ameliorate neuroinflammation and apoptosis in aluminium-induced cognitive impairment rat model

Authors and Affiliations

Mohamed Nabil1, Dina H. Kassem2, Azza A. Ali3, and Hala O. El-Mesallamy2,4

1. Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt
2. Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
3. Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo Egypt
4. Faculty of Pharmacy, Sinai University, Sinai, Egypt

Abstract

Background

Aluminium is an environmental neurotoxin present in our daily life; in food and drinking water. Prolonged exposure to aluminium has been highly linked to dementia and Alzheimer’s disease (AD). Neuroinflammation and apoptosis have been shown to play pivotal roles in AD pathogenesis. Over the past decade, mesenchymal stem cells (MSCs) have made their mark as an efficient novel therapeutic modality for a wide array of diseases, including neurodegenerative disorders. This study aimed to investigate the potential ameliorative effects of adipose tissue-derived MSCs (Ad-MSCs) on neuroinflammatory and apoptotic events induced by aluminium, and the implication of these effects on cognitive dysfunction.

Methods

Ad-MSCs were isolated from rat epidydimal fat-pads and characterized properly afterwards. Aged male rats were randomly allocated into three groups (10 rats/group): group I, control group (normal saline, I.P, daily injection for 4 weeks); group II, AD rats were given Aluminium Chloride AlCl3 (70 mg/kg, I.P, daily injection for 4 weeks); group III, AD/Ad-MSCs rats that received a single dose of Ad-MSCs (2X10^6 cell, I.V per rat) after AD induction. One month after Ad-MSCs transplantation, behavioral tests were conducted, followed by histopathological and biochemical evaluations. Amyloid beta (Aβ) levels were determined by ELISA. Whereas expression levels of Bax, Bcl-2, IL-1β, IL-6, and NGF were assessed using quantitative real time polymerase chain reaction.

Results

Transplantation of Ad-MSCs mitigated cognitive impairment in AlCl3-induced AD rats. Interestingly, Ad-MSCs treated rats exhibited significant reduction in hippocampal Bax/Bcl-2 ratio by 2.4 folds compared to their untreated counterparts. Besides, downregulation of hippocampal expression levels of IL-1β and IL-6 by 11.4 and 10.6 folds, respectively, was observed in Ad-MSCs treated group compared to the untreated one. Moreover, NGF expression was found to be upregulated by 15.9 folds in the hippocampus. These findings were consistent with lower levels of hippocampal Aβ in the Ad-MSCs treated rats compared to the untreated ones (22.23±0.8 vs. 28.07±0.9 pg/mg protein, respectively, p= 0.003).

Conclusions

Ad-MSCs effectively ameliorate cognitive dysfunction induced by aluminium, at least partially, via exhibiting anti-inflammatory, anti-apoptotic and neurogenic effects. These findings shed lights on Ad-MSCs as a promising novel approach for AD treatment.