Related Experiment Video
Updated: Jun 24, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Selective CB2 receptor agonism protects central neurons from remote axotomy-induced apoptosis through the PI3K/Akt
Maria Teresa Viscomi1, Sergio Oddi, Laura Latini
1Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Abstract:
Endocannabinoids are neuroprotective in vivo and in vitro, but the mechanisms by which they act are largely unknown. The present study addressed the role of cannabinoid receptors during remote cell death of central neurons in a model that is based on cerebellar lesions. A lesion in one cerebellar hemisphere induced remote cell death and type 2 cannabinoid receptor (CB2R) expression in contralateral precerebellar neurons. Of the selective agonists and antagonists that modulated cannabinoid receptor activity, we found that the CB2R agonist JWH-015 reduced neuronal loss and cytochrome-c release, leading to neurological recovery; these effects were reversed by the selective CB2R antagonist SR144528. Analysis of CB2R-triggered signal transduction demonstrated that in axotomized neurons, CB2R regulated Akt and JNK phosphorylation through a PI3K-dependent pathway, whereas other major signaling routes that are dependent on CB2R, such as ERK1/2 and p38, were not involved. This result was corroborated by the observation that the selective PI3K inhibitor LY294002 blocked the CB2R stimulation effects on neuronal survival as well as Akt and JNK phosphorylation levels. Together, these data demonstrate that axonal damage induces CB2R expression in central neurons and that stimulation of this receptor has a neuroprotective effect that is achieved through PI3K/Akt signaling.
Insights
Cannabinoid receptors, specifically CB2R, protect central neurons from damage after injury. Activating CB2R enhances neuroprotection via the PI3K/Akt pathway, promoting neurological recovery.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Endocannabinoids exhibit neuroprotective properties, but their precise mechanisms remain unclear.
- Cannabinoid receptors play a role in neuronal survival, particularly in response to injury.
Purpose of the Study:
- To investigate the role of cannabinoid receptors in remote cell death of central neurons following cerebellar lesions.
- To elucidate the signaling pathways involved in CB2R-mediated neuroprotection.
Main Methods:
- Induction of cerebellar lesions in a rodent model to study remote neuronal cell death.
- Administration of selective CB2R agonists (JWH-015) and antagonists (SR144528) to modulate receptor activity.
- Analysis of signaling pathways, including Akt, JNK, ERK1/2, and p38 phosphorylation, using PI3K inhibitors (LY294002).
Main Results:
- Cerebellar lesions induced contralateral precerebellar neuron death and increased CB2R expression.
- JWH-015 treatment reduced neuronal loss and cytochrome-c release, improving neurological function, while SR144528 reversed these effects.
- CB2R activation regulated Akt and JNK phosphorylation via a PI3K-dependent pathway, independent of ERK1/2 and p38.
Conclusions:
- Axonal damage triggers CB2R expression in central neurons.
- Stimulation of CB2R confers neuroprotection through the PI3K/Akt signaling cascade, offering a potential therapeutic target for neuronal injury.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...