Cannabinoid Receptor Type 1 Agonist ACEA Improves Cognitive Deficit on STZ-Induced Neurotoxicity Through Apoptosis Pathway and NO Modulation
Autor: | Andressa Pereira Costa, Andréa da Silva Torrão, Fernanda Crunfli, Talita Aparecida de Moraes Vrechi |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Cannabinoid receptor Cell Survival medicine.medical_treatment Apoptosis Arachidonic Acids Pharmacology Toxicology Nitric Oxide Neuroprotection Streptozocin 03 medical and health sciences Mice 0302 clinical medicine Receptor Cannabinoid CB1 Alzheimer Disease Cell Line Tumor Cannabinoid receptor type 1 medicine Animals Rats Wistar Neuroinflammation Nootropic Agents Cannabinoid Receptor Agonists business.industry General Neuroscience Neurodegeneration Neurotoxicity medicine.disease Endocannabinoid system 030104 developmental biology Neuroprotective Agents Nerve Degeneration Cannabinoid business Cognition Disorders 030217 neurology & neurosurgery |
Zdroj: | Neurotoxicity research. 35(3) |
ISSN: | 1476-3524 |
Popis: | The cannabinoid system has the ability to modulate cellular and molecular mechanisms, including excitotoxicity, oxidative stress, apoptosis, and inflammation, acting as a neuroprotective agent, by its relationship with signaling pathways associated to the control of cell proliferation, differentiation, and survival. Recent reports have raised new perspectives on the possible role of cannabinoid system in neurodegenerative diseases like Alzheimer disease's (AD). AD is a neurodegenerative disorder characterized by the presence of amyloid plaques, neurofibrillary tangles, neuronal death, and progressive cognitive loss, which could be caused by energy metabolism impairment, changes in insulin signaling, chronic oxidative stress, neuroinflammation, Tau hyperphosphorylation, and Aβ deposition in the brain. Thus, we investigated the presumptive protective effect of the cannabinoid type 1 (CB1)-selective receptor agonist arachidonyl-2'-chloroethylamide (ACEA) against streptozotocin (STZ) exposure stimuli in an in vitro neuronal model (Neuro-2a neuroblastoma cells) and in vivo model (intracerebroventricular STZ injection), experimental models of sporadic AD. Our results demonstrated that ACEA treatment reversed cognitive impairment and increased activity of Akt and ERK triggered by STZ, and increased IR expression and increased the anti-apoptotic proteins levels, Bcl-2. In the in vitro model, ACEA was able to rescue cells from STZ-triggered death and modulated the NO release by STZ. Our study has demonstrated a participation of the cannabinoid system in cellular survival, involving the CB1 receptor, which occurs by positive regulation of the anti-apoptotic proteins, suggesting the participation of this system in neurodegenerative processes. Our data suggest that the cannabinoid system is an interesting therapeutic target for the treatment of neurodegenerative diseases. |
Databáze: | OpenAIRE |
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