Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease.
نویسندگان
چکیده
We studied whether combinations of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of Δ(9)-THC- and CBD-enriched botanical extracts. The issue was also studied in malonate-lesioned rats. The administration of Δ(9)-THC- and CBD-enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB(1) receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Δ(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of Δ(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies.
منابع مشابه
Effect of Olive Leaf Extract on the Behavioral Signs of Huntington\'s Disease and Antioxidant Enzymatic Activity in the Rat Brain
Introduction: Huntington's disease is a neurodegenerative disorder in which an increase in the global oxidative stress and a decrease in the antioxidant defense system are observed. Olea europaea's main phenolic components include oleuropein, dimethyl oleuropein, ligstroside and phenolic oleosides, which can be more than 140 mg per gram of fresh olives and 60-90 mg per gram of dried olive le...
متن کاملCannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy...
متن کاملThe therapeutic potential of the endocannabinoid system for Alzheimer's disease.
INTRODUCTION Dementia currently affects over 35 million people worldwide. The most common form of dementia is Alzheimer's disease (AD). Currently, treatments for AD do not stop or reverse the progression of the disease and they are accompanied by side effects. AREAS COVERED The main features of AD pathology, treatment options currently available, the endocannabinoid system and its functionali...
متن کاملNeuroprotective Effects of Myricitrin on Cognitive Deficits in Hippacampal Demyelinated Rats
Background and purpose: Multiple sclerosis (MS) as an autoimmune disease is the most common demyelinating inflammatory disease in young people that affects the central nervous system. Myricitrin (MYR) is known to have antioxidant and neuroprotection effects, so, the current study investigated its effect on cognitive defects in rat models of MS. Materials and methods: In this experimental study...
متن کاملBehavioral study of effects of mesenchymal stem cells transplant on motor deficits improvement in animal model of Huntington\'s disease
Introduction: As an inherited neurodegenerative disease, Huntington's disease is accompanied with wide neuronal degeneration in neostriatum and neocortex. Progress of the disease causes disabling clinical effects on movements, recognition and physiology of the body, and finally results in death. At this stage of knowledge we are, there is no effective therapeutic strategy for diminishing the mo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of neuroscience research
دوره 89 9 شماره
صفحات -
تاریخ انتشار 2011