Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity

Pacheco-Sánchez, Beatriz; Tovar, Rubén; Ben Rabaa, Meriem; Sánchez-Salido, Lourdes; Vargas, Antonio; Suárez, Juan; Rodríguez de Fonseca, Fernando; Rivera, Patricia

doi:10.3390/ijms241612598

Open AccessArticle

Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity

by

Beatriz Pacheco-Sánchez

^1,†

,

Rubén Tovar

^1,†,

Meriem Ben Rabaa

^1,2,

Lourdes Sánchez-Salido

¹,

Antonio Vargas

¹,

Juan Suárez

^1,3

,

Fernando Rodríguez de Fonseca

^1,*

and

Patricia Rivera

^1,*

¹

Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Hospital Universitario Regional de Málaga, 29010 Málaga, Spain

²

Molecular Biotechnology, FH Campus Wien, University for Applied Sciences, Favoritenstraße 222, 1100 Vienna, Austria

³

Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Universidad de Málaga, 29010 Málaga, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(16), 12598; https://doi.org/10.3390/ijms241612598

Submission received: 31 May 2023 / Revised: 28 July 2023 / Accepted: 5 August 2023 / Published: 9 August 2023

(This article belongs to the Special Issue New Trends in Alzheimer's Disease Research: From Molecular Mechanisms to Therapeutics)

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Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca²⁺ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca²⁺ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.

Keywords: 3×Tg-AD-AD mice; Alzheimer’s disease; astrocytes; hippocampus; endocannabinoid system

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MDPI and ACS Style

Pacheco-Sánchez, B.; Tovar, R.; Ben Rabaa, M.; Sánchez-Salido, L.; Vargas, A.; Suárez, J.; Rodríguez de Fonseca, F.; Rivera, P. Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity. Int. J. Mol. Sci. 2023, 24, 12598. https://doi.org/10.3390/ijms241612598

AMA Style

Pacheco-Sánchez B, Tovar R, Ben Rabaa M, Sánchez-Salido L, Vargas A, Suárez J, Rodríguez de Fonseca F, Rivera P. Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity. International Journal of Molecular Sciences. 2023; 24(16):12598. https://doi.org/10.3390/ijms241612598

Chicago/Turabian Style

Pacheco-Sánchez, Beatriz, Rubén Tovar, Meriem Ben Rabaa, Lourdes Sánchez-Salido, Antonio Vargas, Juan Suárez, Fernando Rodríguez de Fonseca, and Patricia Rivera. 2023. "Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity" International Journal of Molecular Sciences 24, no. 16: 12598. https://doi.org/10.3390/ijms241612598

APA Style

Pacheco-Sánchez, B., Tovar, R., Ben Rabaa, M., Sánchez-Salido, L., Vargas, A., Suárez, J., Rodríguez de Fonseca, F., & Rivera, P. (2023). Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity. International Journal of Molecular Sciences, 24(16), 12598. https://doi.org/10.3390/ijms241612598

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Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer’s Disease: Implications for Controlling Astroglial Activity

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