Signalling mechanisms involved in memory function : focus on the effects of Δ9-tetrahydrocannabinol

Galera López, Lorena

Signalling mechanisms involved in memory function : focus on the effects of Δ9-tetrahydrocannabinol

Document Type

Doctoral thesis
Published Version

Author

Galera López, Lorena

Director

Ozaita, Andres
Maldonado, Rafael

Publication Date

2021-09-22

Pages

445 p.

Citation

Galera López, L. Signalling mechanisms involved in memory function : focus on the effects of Δ9-tetrahydrocannabinol. 2021. handle: http://hdl.handle.net/10803/672693

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Memory is a physiological brain function crucial for adaptive behaviour of individuals. Memory alterations are described as impairments in the processes by which memory is perceived, encoded, consolidated, retrieved, or used. there are countless situations that can lead to memory alterations. In this thesis we used specific murine mouse models to study the cellular and molecular mechanisms involved in learning and memory performance in specific situations where memory is compromised. Specifically, we described that repeated non-amnesic low doses of Δ9-tetrahydrocannabinol (THC) affect memory performance through serotonergic signalling in mice. Moreover, we reported specific memory alterations associated to the genetic inhibition of protein kinase C (PKC) gamma gene. Additionally, we revealed the involvement of the PKC-gamma isoform in the amnesic-like effects produced by THC in mice. Overall, combining behavioural, biochemical, and pharmacological approaches we have advanced in the understanding of relevant mechanisms for memory function and dysfunction associated to cannabis exposure.
La memoria es una función fisiológica del cerebro cuyas alteraciones se definen como déficits en la percepción, codificación, consolidación, recuperación o utilización de esta. En esta tesis hemos utilizado modelos específicos de ratón para estudiar los mecanismos celulares y moleculares involucrados en el desempeño del aprendizaje y de la memoria cuando esta se encuentra afectada. Específicamente, describimos que dosis bajas repetidas y no amnésicas de Δ9-tetrahidrocannabinol (THC) afectan al funcionamiento de la memoria a través de la señalización serotoninérgica. Además, reportamos alteraciones de la memoria asociadas a la inhibición genética de la isoforma gamma de la proteína quinasa C (PKC). Por otra parte, mostramos la participación de la isoforma PKC-gamma en los efectos de tipo amnésico producidos por el THC. Combinando enfoques conductuales, bioquímicos y farmacológicos, hemos avanzado en la comprensión de los mecanismos implicados en la función y la disfunción de la memoria asociada a la exposición al cannabis.

Keywords

Memory, PKC-gamma, Δ9-tetrahydrocannabinol (THC), CB1 cannabinoid receptor, 5-HT2A serotonin receptor, Memoria, CB1 receptor cannabinoide, 5-HT2A receptor serotoninérgico