Cannabidiol Ameliorates Cognitive Function via Regulation of IL-33 and TREM2 Upregulation in a Murine Model of Alzheimer’s Disease

Article type: Short Communication

Authors: Khodadadi, Hesam^{a; b} | Salles, Évila Lopes^{a; b} | Jarrahi, Abbas^c | Costigliola, Vincenzo^d | Khan, MB^e | Yu, Jack C.^f | Morgan, John C.^g | Hess, David C.^e | Vaibhav, Kumar^c | Dhandapani, Krishnan M.^c | Baban, Babak^{a; b; *}

Affiliations: [a] Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA, USA | [b] Center for Excellence in Research, Scholarship and Innovation, Dental College of Georgia, Augusta University, Augusta, GA, USA | [c] Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA | [d] European Medical Association (EMA), Brussels, Belgium | [e] Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA | [f] Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA | [g] Parkinson’s Foundation Center of Excellence, Movement Disorders, Program, Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA, USA

Correspondence: [*] Correspondence to: Babak Baban, PhD, MPH, MBA, FAHA, Department of Oral Biology and Diagnostic Sciences, DCG Center for Excellence in Research, Scholarship and Innovation (CERSI) Augusta University, Augusta, GA, USA. E-mail: [email protected].

Abstract: There is a dire need for due innovative therapeutic modalities to improve outcomes of AD patients. In this study, we tested whether cannabidiol (CBD) improves outcomes in a translational model of familial AD and to investigate if CBD regulates interleukin (IL)-33 and triggering receptor expressed on myeloid cells 2 (TREM2), which are associated with improved cognitive function. CBD was administered to 5xFAD mice, which recapitulate early onset, familial AD. Behavioral tests and immunoassays were used to evaluate cognitive and motor outcomes. Our findings suggest that CBD treatment enhanced IL-33 and TREM2 expression, ameliorated the symptoms of AD, and retarded cognitive decline.

Keywords: Alzheimer’s disease, cannabidiol, CBD, dementia, ILC2, innate lymphoid cells

DOI: 10.3233/JAD-210026

Journal: Journal of Alzheimer's Disease, vol. 80, no. 3, pp. 973-977, 2021