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CB2R induces a protective response for epileptic seizure via the PI3K 110α-AKT signaling pathway

Qingjun Cao1, Xueyan Liu1, Fenghua Yang1

  • 1Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Experimental and Therapeutic Medicine
|December 14, 2018
PubMed

Insights

Cannabinoid 2 receptor (CB2R) activation promotes astrocyte proliferation and survival in epilepsy models by activating the PI3K/AKT pathway. This finding offers potential therapeutic targets for epilepsy treatment.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Epilepsy is a chronic neurological disorder characterized by abnormal brain activity.
  • Cannabinoid 2 receptor (CB2R) plays a role in central nervous system (CNS) diseases.

Purpose of the Study:

  • To investigate the effect of CB2R activation on the phosphoinositide 3-kinase (PI3K) 110α-protein kinase B (AKT) signaling pathway in an astrocyte model of epilepsy.

Main Methods:

  • Established an epilepsy cell model using rat CTX TNA2 astrocytes treated with Mg-free solution.
  • Administered CB2R agonist (JWH133) and antagonist (AM630).
  • Performed cell cycle analysis and Western blotting; validated findings in a rat epilepsy model.

Main Results:

  • Mg-free solution inhibited cell cycle progression and downregulated key proteins (cyclin D1, p-Rb, PI3K 110α, p-AKT).
  • JWH133 treatment reversed these effects, promoting cell cycle progression and upregulating proteins.
  • AKT inhibition (wortmannin) blocked JWH133's effects, confirming AKT pathway involvement.

Conclusions:

  • CB2R activation stimulates astrocyte proliferation and survival.
  • This occurs through the activation of the PI3K 110α-AKT signaling pathway.
Keywords:
astrocytecannabinoid 2 receptorepilepsyprotein kinase B

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