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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

Fatin Nadzirah Zakaria1,2★, Mohamad Aris Mohd Moklas1, Mohamad Taufik Hidayat Baharuldin3, Che Norma Mat Taib1, Hasiah Ab Hamid1, Hafizah Abdul Hamid1, Samaila Musa Chiroma4★ Corresponding author

  1. 1Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, MALAYSIA.
  2. 2Department of Basic Sciences, Faculty of Health Sciences, Universiti Teknologi Mara Puncak Alam Campus, Puncak Alam, Selangor, MALAYSIA.
  3. 3Faculty of Medicine and Defense Health, National Defense Universiti of Malaysia, Kem Perdana Sungai Besi, Federal Territory of Kuala Lumpur, MALAYSIA.
  4. 4Newcastle University Medicine Malaysia (NUMed), Kota Ilmu, EduCity, Iskandar Puteri, Johor, MALAYSIA.

CORRESPONDENCE

Fatin Nadzirah Zakaria

Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, MALAYSIA.

fatinn9604@uitm.edu.my

Received: 11-10-2023; Revised: 08-11-2023; Accepted: 05-12-2023.

Volume 16, Issue 1 · pp. 33–41 · PUBLISHED · DOI: 10.5530/jyp.2024.16.5

View on JYP original site ↗

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.

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    Zakaria, F. N., Moklas, M. A. M., Baharuldin, M. T. H., Taib, C. N. M., Hamid, H. A., Hamid, H. A., & Chiroma, S. M. (). Delta-9-tetrahydrocannabinol Ameliorates D-galactose/ Aluminium Chloride-Induced Alzheimer’s-Like Cognitive Deficit in Rats via Neurogenesis in their Hippocampus. Journal of Young Pharmacists, 16(1), 33–41. https://doi.org/10.5530/jyp.2024.16.5