Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer's Disease

International audienceAging can lead to decline in cognition, notably due to neurodegenerative processes overwhelming the brain over time. As people live longer, numerous concerns are rightfully raised toward long-term slowly incapacitating diseases with no cure, such as Alzheimer's disease. Since the early 2000's, the role of neuroinflammation has been scrutinized for its potential role in the development of diverse neurodegenerative diseases notably because of its slow onset and chronic nature in aging. Despite the lack of success yet, treatment of chronic neuroinflammation could help alleviate process implicated in neurodegenerative disease. A growing number of studies including our own have aimed at the endocannabinoid system and unfolded unique effects of this system on neuroinflammation, neurogenesis and hallmarks of Alzheimer's disease and made it a reasonable target in the context of normal and pathological brain aging. Alzheimer's disease (AD) is the most common neurodegenerative disease and accounts for the majority of diagnosed dementia after age 60. It is estimated to currently affect between 20 and 30 million people worldwide with an incidence of the disease between 3 and 30% over the age of 60 [1]. As life expectancy increases, the prevalence of AD and its burden on healthcare is very likely to increase dramatically in the next few decades. Currently available drugs do not reverse or stop the progression of the disease, but only relieve certain cognitive symptoms and thus provide no cure for this growing health and economic concern. Alzheimer's diseas

Can the benefits of cannabinoid receptor stimulation on neuroinflammation, neurogenesis and memory during normal aging be useful in AD prevention?

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease has become a growing socio-economical concern in developing countries where increased life expectancy is leading to large aged populations. While curing Alzheimer's disease or stopping its progression does not appear within reach in a foreseeable future, new therapies capable of delaying the pathogenesis would represent major breakthroughs.</p> <p>Presentation of the hypothesis</p> <p>The growing number of medical benefits of cannabinoids, such as their ability to regulate age-related processes like neuroinflammation, neurogenesis and memory, raise the question of their potential role as a preventive treatment of AD.</p> <p>Testing the hypothesis</p> <p>To test this hypothesis, epidemiological studies on long term, chronic cannabinoid users could enlighten us on the potential benefits of these compounds in normal and pathological ageing processes. Systematic pharmacological (and thus more mechanistic) investigations using animal models of Alzheimer's disease that have been developed would also allow a thorough investigation of the benefits of cannabinoid pharmacotherapy in the pathogenesis of Alzheimer's disease.</p> <p>Implications of the hypothesis</p> <p>The chronic administration of non-selective cannabinoids may delay the onset of cognitive deficits in AD patients; this will dramatically reduce the socio-economic burden of AD and improve the quality of life of the patients and their families.</p

Electron-impact broadening of the 3s-3p lines in low-Z Li-like ions

The collisional electron-impact line widths of the 3s-3p transitions in Li-like ions from B III to Ne VIII are calculated with the convergent close-coupling (CCC) method from the atomic collision theory. The elastic and inelastic contributions to the line broadening and their Z-scaling are discussed in detail, and comparisons with recent experimental and theoretical results are also presented. It is found that similar to our previous study of line broadening in Be-like ions, the difference between experimental and CCC results monotonically increases with the spectroscopic charge of an ion.Comment: 23 pages, 8 figures, 1 table. To be published in JQSR

Stark Broadening of the B III 2s-2p Lines

We present a quantum-mechanical calculation of Stark line widths from electron-ion collisions for the $2s_{1/2}-2p_{1/2,3/2}$, lambda = 2066 and 2067 A, resonance transitions in B III. The results confirm the previous quantum-mechanical R-matrix calculations but contradict recent measurements and semi-classical and some semi-empirical calculations. The differences between the calculations can be attributed to the dominance of small L partial waves in the electron-atom scattering, while the large Stark widths inferred from the measurements would be substantially reduced if allowance is made for hydrodynamic turbulence from high Reynolds number flows and the associated Doppler broadening.Comment: 21 pages, 4 figures; to be published in Phys. Rev.

Cannabinoids and Dementia: A Review of Clinical and Preclinical Data

The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia. We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD). Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro. However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce. While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia. Further research is needed, including in vivo models of dementia and human studies

Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

Background: Alzheimer’s disease (AD) brain shows an ongoing inflammatory condition and non-steroidal antiinflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and antiinflammatory agents with therapeutic potential. Methods: We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). Results: Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-a mRNA expression found in the AD model. Increased cortical b-amyloid (Ab) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Ab transport across choroid plexus cells in vitro. Conclusions: In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Ab clearanceThis work was supported by the Spanish Ministry of Science and Technology (SAF 2005-02845 to M.L.C). A.M.M-M. was recipient a fellowship from the Ministry of Education and Scienc

Comparative study of argon 3p electron-impact ionization at low energies

(c) 2001 The American Physical SocietyAn experimental and theoretical study of electron-impact ionization of the 3p orbital in argon is presented. The (e,2e) technique was used to measure the relative triple-differential cross section for this process in the coplanar asymmetric geometry. The experimental results were obtained at an incident electron energy of 113.5 eV, a scattering angle of 15°, and ejected electron energies of 10, 7.5, 5, and 2 eV. The experimental data are compared with a distorted-wave Born approximation (DWBA) calculation, and also with previous results for argon 3s ionization obtained under identical kinematic conditions. Discrepancies between the experimental and theoretical data are attributed to the effects of charge-cloud polarization and higher-order scattering processes, which are not incorporated in the DWBA calculation.Haynes, Matthew A. and Lohmann, Birgi