Canna~Fangled Abstracts

CB2 cannabinoid agonist enhanced neurogenesis in GFAP/Gp120 transgenic mice displaying deficits in neurogenesis

By October 22, 2013No Comments

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Research Paper

CB2 cannabinoid agonist enhanced neurogenesis in GFAP/Gp120 transgenic mice displaying deficits in neurogenesis

  1. Hava Karsenty Avraham1,
  2. Shuxian Jiang1,
  3. Yigong Fu1,
  4. Edward Rockenstein2,
  5. Alexandros Makriyannis3,
  6. Alexander Zvonok3,
  7. Eliezer Masliah2,
  8. Shalom Avraham1,*

DOI: 10.1111/bph.12478

Additional Information(Show All)

Author InformationPublication History

  1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/bph.12478

Keywords:

  • CB2 agonist;
  • neural progenitor cells;
  • HIV-1 Gp120 protein;
  • GFAP/Gp120 transgenic mice;
  • neurogenesis

Summary

Background and purpose

HIV-1 glycoprotein Gp120 induces apoptosis in rodent and human neurons in vitro and in vivo. HIV-1/Gp120 is involved in the pathogenesis of HIV-associated dementia (HAD) and inhibits proliferation of adult neural progenitor cells (NPCs) in GFAP/Gp120 transgenic (Tg) mice. Since cannabinoids exert neuroprotective effects in several model systems, we examined the protective effects of CB2 agonist AM1241 on Gp120-mediated insults on neurogenesis.

Experimental approach

The effects of AM1241 on NPCs were examined in vitro and in vivo using GFAP/Gp120 transgenic mice.

Key results

AM1241 inhibited in vitro Gp120-mediated neurotoxicity and apoptosis of primary human and murine NPCs and increased their survival. In addition, AM1241 agonist promoted differentiation of NPCs to neuronal cells. While GFAP/Gp120 Tg mice exhibited impaired neurogenesis, as indicated by reduction in BrdU+ cells and doublecortin+ (DCX+) cells as well as a decrease in the number of 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+ cells and PCNA+ cells. Further, a significant decrease in astrogliosis and gliogenesis was observed in GFAP/Gp120 Tg mice treated with AM1241 as compared to those treated with vehicle control.

Conclusions and implications

CB2 agonist rescued impaired neurogenesis caused by HIV-1/Gp120 insult. Thus, CB2 agonists may act as neuroprotective agents for rescuing impaired neurogenesis in HAD patients.
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