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Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice

Endocannabinoid system activity declines with age in the hippocampus, along with the density of the cannabinoid receptor type-1 (CB1). This process might contribute to brain ageing, as previous studies showed that the constitutive deletion of the CB1 receptor in mice leads to early onset of memory d...

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Autores principales: Palmisano, Michela, Gargano, Alessandra, Olabiyi, Bolanle Fatimat, Lutz, Beat, Bilkei-Gorzo, Andras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819823/
https://www.ncbi.nlm.nih.gov/pubmed/36613469
http://dx.doi.org/10.3390/ijms24010026
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author Palmisano, Michela
Gargano, Alessandra
Olabiyi, Bolanle Fatimat
Lutz, Beat
Bilkei-Gorzo, Andras
author_facet Palmisano, Michela
Gargano, Alessandra
Olabiyi, Bolanle Fatimat
Lutz, Beat
Bilkei-Gorzo, Andras
author_sort Palmisano, Michela
collection PubMed
description Endocannabinoid system activity declines with age in the hippocampus, along with the density of the cannabinoid receptor type-1 (CB1). This process might contribute to brain ageing, as previous studies showed that the constitutive deletion of the CB1 receptor in mice leads to early onset of memory deficits and histological signs of ageing in the hippocampus including enhanced pro-inflammatory glial activity and reduced neurogenesis. Here we asked whether the CB1 receptor exerts its activity locally, directly influencing hippocampal ageing or indirectly, accelerating systemic ageing. Thus, we deleted the CB1 receptor site-specifically in the hippocampus of 2-month-old CB1(flox/flox) mice using stereotaxic injections of rAAV-Cre-Venus viruses and assessed their social recognition memory four months later. Mice with hippocampus-specific deletion of the CB1 receptor displayed a memory impairment, similarly as observed in constitutive knockouts at the same age. We next analysed neuroinflammatory changes in the hippocampus, neuronal density and cell proliferation. Site-specific mutant mice had enhanced glial cell activity, up-regulated levels of TNFα in the hippocampus and decreased cell proliferation, specifically in the subgranular zone of the dentate gyrus. Our data indicate that a local activity of the CB1 receptor in the hippocampus is required to maintain neurogenesis and to prevent neuroinflammation and cognitive decline.
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spelling pubmed-98198232023-01-07 Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice Palmisano, Michela Gargano, Alessandra Olabiyi, Bolanle Fatimat Lutz, Beat Bilkei-Gorzo, Andras Int J Mol Sci Article Endocannabinoid system activity declines with age in the hippocampus, along with the density of the cannabinoid receptor type-1 (CB1). This process might contribute to brain ageing, as previous studies showed that the constitutive deletion of the CB1 receptor in mice leads to early onset of memory deficits and histological signs of ageing in the hippocampus including enhanced pro-inflammatory glial activity and reduced neurogenesis. Here we asked whether the CB1 receptor exerts its activity locally, directly influencing hippocampal ageing or indirectly, accelerating systemic ageing. Thus, we deleted the CB1 receptor site-specifically in the hippocampus of 2-month-old CB1(flox/flox) mice using stereotaxic injections of rAAV-Cre-Venus viruses and assessed their social recognition memory four months later. Mice with hippocampus-specific deletion of the CB1 receptor displayed a memory impairment, similarly as observed in constitutive knockouts at the same age. We next analysed neuroinflammatory changes in the hippocampus, neuronal density and cell proliferation. Site-specific mutant mice had enhanced glial cell activity, up-regulated levels of TNFα in the hippocampus and decreased cell proliferation, specifically in the subgranular zone of the dentate gyrus. Our data indicate that a local activity of the CB1 receptor in the hippocampus is required to maintain neurogenesis and to prevent neuroinflammation and cognitive decline. MDPI 2022-12-20 /pmc/articles/PMC9819823/ /pubmed/36613469 http://dx.doi.org/10.3390/ijms24010026 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palmisano, Michela
Gargano, Alessandra
Olabiyi, Bolanle Fatimat
Lutz, Beat
Bilkei-Gorzo, Andras
Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title_full Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title_fullStr Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title_full_unstemmed Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title_short Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice
title_sort hippocampal deletion of cb1 receptor impairs social memory and leads to age-related changes in the hippocampus of adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819823/
https://www.ncbi.nlm.nih.gov/pubmed/36613469
http://dx.doi.org/10.3390/ijms24010026
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