» Articles » PMID: 23108550

The Endocannabinoid System in Normal and Pathological Brain Ageing

Overview
Specialty Biology
Date 2012 Oct 31
PMID 23108550
Citations 66
Authors
Affiliations
Soon will be listed here.
Abstract

The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

Citing Articles

The Complex Relationship Between Cannabis Use and Mental Health: Considering the Influence of Cannabis Use Patterns and Individual Factors.

Sagar K, Gruber S CNS Drugs. 2025; 39(2):113-125.

PMID: 39753766 DOI: 10.1007/s40263-024-01148-2.


Bidirectional Effect of Long-Term Δ-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome.

Bilkei-Gorzo A, Schurmann B, Schneider M, Kraemer M, Nidadavolu P, Beins E ACS Pharmacol Transl Sci. 2024; 7(9):2637-2649.

PMID: 39296258 PMC: 11406684. DOI: 10.1021/acsptsci.4c00002.


Data-driven dynamic profiles of tonic heat pain perception in pain-free volunteers are associated with differences in anandamide levels.

Potvin S, Vincenot M, Haroune L, Giguere C, Gendron L, Leonard G Sci Rep. 2024; 14(1):17238.

PMID: 39060336 PMC: 11282288. DOI: 10.1038/s41598-024-67401-2.


Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation.

Armeli F, Mengoni B, Laskin D, Businaro R Curr Issues Mol Biol. 2024; 46(7):6868-6884.

PMID: 39057052 PMC: 11276139. DOI: 10.3390/cimb46070410.


The Neurotherapeutic Arsenal in : Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects.

Al-Khazaleh A, Zhou X, Bhuyan D, Munch G, Al-Dalabeeh E, Jaye K Molecules. 2024; 29(2).

PMID: 38257323 PMC: 10821245. DOI: 10.3390/molecules29020410.


References
1.
Vara D, Salazar M, Olea-Herrero N, Guzman M, Velasco G, Diaz-Laviada I . Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ. 2011; 18(7):1099-111. PMC: 3131949. DOI: 10.1038/cdd.2011.32. View

2.
Ricciarelli R, dAbramo C, Massone S, Marinari U, Pronzato M, Tabaton M . Microarray analysis in Alzheimer's disease and normal aging. IUBMB Life. 2004; 56(6):349-54. DOI: 10.1080/15216540412331286002. View

3.
Derkinderen P, Valjent E, Toutant M, Corvol J, Enslen H, Ledent C . Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus. J Neurosci. 2003; 23(6):2371-82. PMC: 6742049. View

4.
Berrendero F, Romero J, Suarez I, de la Cruz P, Ramos J, Fernandez-Ruiz J . Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats. Biochim Biophys Acta. 1998; 1407(3):205-14. DOI: 10.1016/s0925-4439(98)00042-8. View

5.
Toescu E . Normal brain ageing: models and mechanisms. Philos Trans R Soc Lond B Biol Sci. 2005; 360(1464):2347-54. PMC: 1569594. DOI: 10.1098/rstb.2005.1771. View