Protective Effects of the Synthetic Cannabinoids CP55,940 and JWH-015 on Rat Brain Mitochondria upon Paraquat Exposure

@article{VelezPardo2010ProtectiveEO,
  title={Protective Effects of the Synthetic Cannabinoids CP55,940 and JWH-015 on Rat Brain Mitochondria upon Paraquat Exposure},
  author={Carlos Velez-Pardo and Marlene Jimenez-Del-Rio and Silvia Lores-Arnaiz and Juanita Bustamante},
  journal={Neurochemical Research},
  year={2010},
  volume={35},
  pages={1323-1332}
}
The effects of cannabinoids in mitochondria after acute oxidative stress insult are not fully established. We investigated the ability of CP55,940 and JWH-015 to scavenge reactive oxygen species and their effect on mitochondria permeability transition (MPT) in either a mitochondria-free superoxide anion generation system, intact rat brain mitochondria or in sub-mitochondrial particles (SMP) treated with paraquat (PQ). Oxygen consumption, mitochondrial membrane potential (Δψm) and MPT were… 

Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins

The data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.

Effect of the MAGL/FAAH Dual Inhibitor JZL-195 on Streptozotocin-Induced Alzheimer's Disease-like Sporadic Dementia in Mice with an Emphasis on Aβ, HSP-70, Neuroinflammation, and Oxidative Stress.

Investigation of the possible neuroprotective potential of the dual MAGL/FAAH inhibitor JZL-195 against ICV-STZ-induced sporadic Alzheimer's disease in Swiss albino mice shows significant reversal of the biochemical anomalies, suggesting its therapeutic potential against the sporadic Alzheimer’s disease model.

Cannabinoids and mitochondria

Historical and recent evidence of the cannabinoid impact on mitochondrial functions in peripheral and central organs of the body is summarized.

Multi-Target Effects of the Cannabinoid CP55940 on Familial Alzheimer's Disease PSEN1 E280A Cholinergic-Like Neurons: Role of CB1 Receptor.

The findings suggest that the combination of cannabinoids, CB1Rs inverse agonists, and anti-Aβ antibodies might be a promising therapeutic approach for the treatment of familial AD.

Cannabinoids as potential new therapeutics of gastrointestinal motility and inflammatory disorders

Two studies show that cannabinoid-mediated inhibition of guinea-pig ileum contractions is not mediated through the CB1, CB2, CBe or GPR55 receptor, and the approach of attaching a dendrimer to JWH007 to prevent central nervous system penetration does not appear to be a feasible approach.

The endocannabinoid system in normal and pathological brain ageing

  • A. Bilkei-Gorzo
  • Biology
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2012
In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes.

References

SHOWING 1-10 OF 47 REFERENCES

Paraquat induces apoptosis in human lymphocytes: Protective and rescue effects of glucose, cannabinoids and insulin-like growth factor-1

Evidence is provided that PQ induces apoptosis in lymphocytes in a concentration- and time-dependent fashion by an oxidative stress mechanism involving O2√ − , H2O2/(√OH) generation, simultaneous activation of NF-κB/p53/c-Jun transcription factors, mitochondrial depolarization and caspase-3 activation leading to morphological apoptosis.

Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1

The results strongly suggest that CB1 is not involved in the cellular antioxidant neuroprotective effects of cannabinoids, and the role of CB1 in neuroprotection is elucidated.

Avoidance of Abeta[(25-35)] / (H(2)O(2)) -induced apoptosis in lymphocytes by the cannabinoid agonists CP55,940 and JWH-015 via receptor-independent and PI3K-dependent mechanisms: role of NF-kappaB and p53.

The results suggest that CP55,940/( JWH-015) protection/rescue of PBL from noxious stimuli is determined by p53 inactivation, which may contribute to a better understanding of the role played by cannabinoids as neuroprotective agents to target and interrupt molecular signaling that induce damage in AD disorder.

Chronic cannabinoid, CP-55,940, administration alters biotransformation in the rat.

Involvement of Protein Kinase A in Cannabinoid Receptor-Mediated Protection from Oxidative Neuronal Injury

The effect of CB1R activation on oxidative injury, which has been implicated in neuronal death after cerebral ischemia and neurodegenerative disorders, is investigated in mouse cortical neuron cultures and points to a protective mechanism that involves signaling through Gi/o proteins.