The scientists at Picower Institute for Learning and Memory at Massachusetts Institute of Technology used mice which were genetically altered to carry a gene that is most commonly found in children with autism.
Fragile X Syndrome (FXS), which is the leading inherited cause of mental retardation and the most common genetic cause of autism is linked to a mutated X chromosome gene called the fragile X mental retardation 1 (FMR1) gene; when mutated this gene can cause anything from mild learning disabilities to severe autism.
The FXS mice showed abnormalities similar to those in FXS patients, including hyperactivity, purposelessness, repetitive movements, attention deficits and difficulty with learning and memory.
When the enzyme P21-activated kinase (PAK) was inhibited in the study with the FXS mice, electrical communication between neurons in the brains of the mice were restored and their behavioral abnormalities were corrected.
The researchers suggest that by inhibiting PAK the debilitating symptoms of FXS in children could also possibly be countered.
Co-author Susumu Tonegawa, a Picower Professor of Biology and Neuroscience, says the results were intriguing because it suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children.
The study will be published in the online early edition of the Proceedings of the National Academy of Sciences.
These changes contributed to the ability of these mice to fend off weight gain despite a high-fat diet and lack of exercise. Together these results suggest that a CD38 deficiency has a protective effect against high-fat, diet-induced obesity, Dr. Chini says.
Dr. Chini and colleagues also examined the effects of resveratrol in mice. Resveratrol is a naturally occurring substance found in some plants such as mulberries, peanuts and red grapes used to make wine. It has been marketed as a drug that mimics the effects of moderate exercise without the physical act of exercising and also as a longevity drug, despite the lack of evidence that resveratrol is safe and effective in humans.
Mice with CD38 were treated with 30 milligrams (mg) of resveratrol per day. And, to determine the effects of the SIRT genes on obesity, mice without CD38 received the same dose of sirtinol, a drug that shuts down the SIRT genes.
Researchers found that mice with CD38 that were treated with resveratrol for two weeks were protected from high-fat, diet-induced obesity. By contrast, the protective effect against high-fat, diet-induced obesity in the absence of CD38 in mice was invalidated by sirtinol. Mice without CD38 that were treated with sirtinol gained a statistically significant amount of weight when compared with mice without the gene who were not treated with sirtinol.
This data supports the novel notion that CD38 modulates high-fat, diet-induced obesity by a SIRT- dependent mechanism.
Together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity, the authors write.
The authors say the study's results are promising and should be explored in follow-up studies that will focus on the quality of life and longevity in mice.
mayoclinic/