Delta-9-tetrahydrocannabinol Ameliorates D-galactose/ Aluminium Chloride-Induced Alzheimer’s-Like Cognitive Deficit in Rats via Neurogenesis in their Hippocampus

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Delta-9-tetrahydrocannabinol Ameliorates D-galactose/ Aluminium Chloride-Induced Alzheimer’s-Like Cognitive Deficit in Rats via Neurogenesis in their Hippocampus
J Young Pharm. Vol 16/Issue 1/2024 
Fatin Nadzirah Zakaria2,1, Mohamad Aris Mohd Moklas1, Mohamad Taufik Hidayat Baharuldin3, Che Norma Mat Taib1, Hasiah Ab Hamid1, Hafizah Abdul Hamid1 and Samaila Musa Chiroma4
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1Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, MALAYSIA

2Department of Basic Sciences, Faculty of Health Sciences, Universiti Teknologi Mara Puncak Alam Campus, Puncak Alam, Selangor, MALAYSIA

3Faculty of Medicine and Defense Health, National Defense Universiti of Malaysia, Kem Perdana Sungai Besi, Federal Territory of , Kuala Lumpur, MALAYSIA

4Newcastle University Medicine Malaysia (NUMed), Kota Ilmu, EduCity, Iskandar Puteri, Johor, MALAYSIA

Corresponding author.

Correspondence: Dr. Fatin Nadzirah Binti Zakaria Department of Basic Sciences, Faculty of Health Sciences, Universiti Teknologi Mara, Puncak Alam Campus, 42300 Puncak Alam, Selangor, MALAYSIA. Email: fatinn9604@uitm.edu.my
Received October 11, 2023; Revised November 08, 2023; Accepted December 05, 2023.
Copyright 2024 Authors
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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Published in: Journal of Young Pharmacists, 2024; 16(1): 33-41. Published online: 07 July 2025DOI: 10.5530/jyp.2024.16.5

ABSTRACT

Background: Chronic administration of D-galactose and aluminium chloride (D-gal/AlCl3) has been associated with neurodegenerative diseases, such as Alzheimer’s disease (AD). Delta- 9-tetrahydrocannabinol (Δ9THC) is the key psychoactive constituent in Cannabis sativa and has shown promising memory-enhancing capability. This study evaluated the therapeutic effects of Δ9THC on D-gal/AlCl3-induced AD-like rat models through behavioural and histological analysis. Materials and Methods: Healthy male Wistar rats were subjected to AD induction by administering D-gal (60 mg/kg, intraperitoneal injection) and AlCl3 (200 mg/kg, oral) once daily for 10 consecutive weeks. Afterwards, Δ9THC (0.75 mg/kg, 1.5 mg/kg, and 3.0 mg/kg) were administered for 28 days as a treatment phase. Morris Water Maze (MWM) was employed to assess the rats’ behaviour. The structural abnormalities in the hippocampus and neurogenesis markers were assessed. Results: Treatment with Δ9THC alleviated the cognitive dysfunction, as recorded from the MWM, and restored the morphological aberrations in the rat’s hippocampus. Additionally, Δ9THC boosted neurogenesis by marked increased in GFAP+ cells, DCX+ cells, NeuN immunoreactivity and calbindin+ cells. Conclusion: In conclusion, Δ9THC ameliorates D-gal/ AlCl3-induced AD-like cognitive deficits in rat models, which could be linked to its ability to enhance neurogenesis.

Keywords: Aluminium chloride, Alzheimer’s disease, Δ9THC, Cognitive dysfunction, D- galactose, Neurogenesis