Canna~Fangled Abstracts

A selective CB2R agonist (JWH133) restores neuronal circuit after Germinal Matrix Hemorrhage in the preterm via CX3CR1+ microglia.

By January 30, 2016No Comments
Neuropharmacology. 2017 Jan 30. pii: S0028-3908(17)30028-X. doi: 10.1016/j.neuropharm.2017.01.027.
[Epub ahead of print]

Abstract

pm-2-site-207Microglia play dual roles after germinal matrix hemorrhage, and the neurotrophic phenotype maybe neuroprotective. However, the phenotype transformation and the way by which neuron-microglia dialogue remain unclear. We raise the hypothesis that a cannabinoid receptor2 agonist (JWH133) accelerates the CX3CR1+ microglia secreting neurotrophic factors and restores damaged neuronal circuit. Here, we report a novel function of JWH133 in transforming the microglia CX3CR1 positive that secrete brain-derived neurotrophic factor (BDNF), which triggers neuron proliferation and neuronal restoration. Using a collagen VII-induced GMH model in rat pups postnatal day 7 (P7), we found that the drug showed robust activity in neuronal precursors. Moreover, the FA value of DTI in the internal zone revealed the positive effects of JWH133 on neural restoration. CX3CR1, a critical modulating molecule expressed in microglia, was upregulated after treatment with JWH133 and the corresponding shRNA (NM_133534.1) was used to silence the expression of CX3CR1. 3 days after treatment with JWH133, we detected reduced expression of biomarkers for neural progenitor cells (NPCs) in pups pre-injected in the lateral ventricular tissue with CX3CR1 shRNA, but not in pups injected with control shRNA. Overall, this study provides evidence that JWH133 promoted a neurotrophic phenotype of microglia (CX3CR1+ microglia), beyond merely alleviating microglial proliferation and inflammation. Moreover, JWH133 restored impaired neuronal circuit, which represent a novel therapeutic strategy following GMH in clinic.

KEYWORDS:

CB2R agonist; CX3CR1(+) microglia; Germinal matrix hemorrhage; Neural circuit restoration; Neuron-microglia dialogue

PMID: 28153531

 

DOI: 10.1016/j.neuropharm.2017.01.027
[PubMed – as supplied by publisher]
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