Cannabinoid 1 receptor signaling on GABAergic neurons influences astrocytes in the ageing brain. Academic Article uri icon

Overview

abstract

  • Astrocytes, key regulators of brain homeostasis, interact with neighboring glial cells, neurons and the vasculature through complex processes involving different signaling pathways. It is not entirely clear how these interactions change in the ageing brain and which factors influence astrocyte ageing. Here, we investigate the role of endocannabinoid signaling, because it is an important modulator of neuron and astrocyte functions, as well as brain ageing. We demonstrate that mice with a specific deletion of CB1 receptors on GABAergic neurons (GABA-Cnr1-/- mice), which show a phenotype of accelerated brain ageing, affects age-related changes in the morphology of astrocytes in the hippocampus. Thus, GABA-Cnr1-/- mice showed a much more pronounced age-related and layer-specific increase in GFAP-positive areas in the hippocampus compared to wild-type animals. The number of astrocytes, in contrast, was similar between the two genotypes. Astrocytes in the hippocampus of old GABA-Cnr1-/- mice also showed a different morphology with enhanced GFAP-positive process branching and a less polarized intrahippocampal distribution. Furthermore, astrocytic TNFα levels were higher in GABA-Cnr1-/- mice, indicating that these morphological changes were accompanied by a more pro-inflammatory function. These findings demonstrate that the disruption of endocannabinoid signaling on GABAergic neurons is accompanied by functional changes in astrocyte activity, which are relevant to brain ageing.

publication date

  • August 16, 2018

Research

keywords

  • Aging
  • GABAergic Neurons
  • Receptor, Cannabinoid, CB1
  • Tumor Necrosis Factor-alpha

Identity

PubMed Central ID

  • PMC6095551

Scopus Document Identifier

  • 85053418503

Digital Object Identifier (DOI)

  • 10.1016/j.jneuroim.2006.11.018

PubMed ID

  • 30114280

Additional Document Info

volume

  • 13

issue

  • 8