The cannabinoid CB2 receptor agonist AM1241 enhances neurogenesis in GFAP/Gp120 transgenic mice displaying deficits in neurogenesis.
Br J Pharmacol
; 171(2): 468-79, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24148086
ABSTRACT
BACKGROUND AND PURPOSE:
HIV-1 glycoprotein Gp120 induces apoptosis in rodent and human neurons in vitro and in vivo.â HIV-1/Gp120 is involved in the pathogenesis of HIV-associated dementia (HAD) and inhibits proliferation of adult neural progenitor cells (NPCs) in glial fibrillary acidic protein (GFAP)/Gp120 transgenic (Tg) mice. As cannabinoids exert neuroprotective effects in several model systems, we examined the protective effects of the CB2 receptor agonist AM1241 on Gp120-mediated insults on neurogenesis. EXPERIMENTALAPPROACH:
We assessed the effects of AM1241 on survival and apoptosis in cultures of human and murine NPCs with immunohistochemical and TUNEL techniques. Neurogenesis in the hippocampus of GFAP/Gp120 transgenic mice in vivo was also assessed by immunohistochemistry. KEYRESULTS:
AM1241 inhibited in vitroâ Gp120-mediated neurotoxicity and apoptosis of primary human and murine NPCs and increased their survival. AM1241 also promoted differentiation of NPCs to neuronal cells. While GFAP/Gp120 Tg mice exhibited impaired neurogenesis, as indicated by reduction in BrdU⺠cells and doublecortin⺠(DCXâº) cells, and a decrease in cells with proliferating cell nuclear antigen (PCNA), administration of AM1241 to GFAP/Gp120 Tg mice resulted in enhanced in vivo neurogenesis in the hippocampus as indicated by increase in neuroblasts, neuronal cells, BrdU⺠cells and PCNA⺠cells. Astrogliosis and gliogenesis were decreased in GFAP/Gp120 Tg mice treated with AM1241, compared with those treated with vehicle. CONCLUSIONS AND IMPLICATIONS The CB2 receptor agonist rescued impaired neurogenesis caused by HIV-1/Gp120 insult. Thus, CB2 receptor agonists may act as neuroprotective agents, restoring impaired neurogenesis in patients with HAD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína gp120 do Envelope de HIV
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Receptor CB2 de Canabinoide
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Neurogênese
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Proteína Glial Fibrilar Ácida
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article