Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
Rodríguez de Fonseca, Fernando
Pavón, Francisco Javier
MetadataShow full item record
Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.
Is part ofCellular Neuroscience, 2015, vol. 9, núm. 379, p. 1-14
European research projects
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by (c) Rodríguez de Fonseca, Fernando et al., 2015
Showing items related by title, author, creator and subject.
Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat Blanco Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodríguez de Fonseca, Fernando (Frontiers Media S.A., 2014-01-08)Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated ...
Localization of peroxisome proliferator-activated receptor alpha (PPARa) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Blanco Calvo, Eduardo; Serrano, Antonia; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Suárez, Juan (Frontiers Media S.A., 2014-03-17)The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D ...
Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum Rivera, Patricia; Silva Peña, Daniel; Blanco Calvo, Eduardo; Vargas, Antonio; Arrabal, Sergio; Serrano, Antonia; Pavón, Francisco Javier; Bindila, Laura; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan (Elsevier, 2019-03-01)Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects ...