ABSTRACT
Cannabinoids have been shown to increase neurogenesis in adult brain, as well as protect neurons from excitotoxicity, calcium influx, inflammation, and ischemia. Recent studies have shown that synthetic cannabinoids can alleviate water maze impairments in rats treated with intracranial amyloid beta protein (Abeta); however it is unknown whether this effect is due to the cannabinoids' anti-inflammatory properties or whether it affects Abeta processing. Here we investigate whether cannabinoids have any effect on Alzheimer's disease in vivo. We found that HU210, a potent synthetic cannabinoid, did not improve water maze performance or a contextual fear conditioning task in an APP23/PS45 double transgenic mouse model of AD. HU210 had no effect on APP processing and Abeta generation, as well as neuritic plaque formation in the brains of AD transgenic mice. Our study showed that synthetic cannabinoid HU210 had no beneficial effects on AD neuropathology and behavioral deficits of AD model mice, which advises caution of such drug's application in AD therapies.
Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Cannabinoid Receptor Modulators/agonists , Dronabinol/analogs & derivatives , Memory Disorders/drug therapy , Neuroprotective Agents/pharmacology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/drug effects , Amyloid beta-Protein Precursor/metabolism , Animals , Brain/metabolism , Brain/pathology , Cannabinoid Receptor Modulators/metabolism , Cognition Disorders/drug therapy , Cognition Disorders/metabolism , Cognition Disorders/pathology , Conditioning, Psychological/drug effects , Conditioning, Psychological/physiology , Disease Models, Animal , Dronabinol/pharmacology , Dronabinol/therapeutic use , Female , Humans , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory/drug effects , Memory Disorders/metabolism , Memory Disorders/pathology , Mice , Mice, Transgenic , Plaque, Amyloid/drug effects , Plaque, Amyloid/metabolism , Plaque, Amyloid/pathology , Treatment FailureABSTRACT
The Douglas Mental Health University Institute, in collaboration with the McGill Centre for Studies in Aging, organized a 2-day symposium entitled "Biological Changes Associated with Healthy Versus Pathological Aging" that was held in 13 and 14 December 2007 on the Douglas campus. The symposium involved presentations on current trends in aging and dementia research across several sub-disciplines: genetics, neurochemistry, structural and functional neuroimaging and clinical treatment and rehabilitation. The goal of this symposium was to provide a forum for knowledge-transfer between scientists and clinicians with different specializations in order to promote cross-fertilization of research ideas that would lead to future collaborative neuroscience research in aging and dementia. In this review article, we summarize the presentations made by the 13 international scientists at the symposium and highlight: (i) past research, and future research trends in neuroscience of aging and dementia and (ii) links across levels of analysis that can lead to fruitful transdisciplinary research programs that will advance knowledge about the neurobiological changes associated with healthy aging and dementia.
