Researchers discover new link to schizophrenia

Neuroscientists at Johns Hopkins have discovered that mice lacking an enzyme that contributes to Alzheimer disease exhibit a number of schizophrenia-like behaviors. The finding raises the possibility that this enzyme may participate in the development of schizophrenia and related psychiatric disorders and therefore may provide a new target for developing therapies.

The BACE1 enzyme, for beta-site amyloid precursor protein cleaving enzyme, generates the amyloid proteins that lead to Alzheimer’s disease. The research team years ago suspected that removing BACE1 might prevent Alzheimer.

“We knew at the time that in addition to amyloid precursor protein, BACE1 interacts with other proteins but we didn’t know how those interactions might affect behavior,” says Alena Savonenko, M.D., Ph.D., an assistant professor in neuropathology at Hopkins.

Reporting in the Proceedings of the National Academies of Sciences, the research team describes how mice lacking the BACE1 enzyme show deficits in social recognition among other behaviors classically linked to schizophrenia.

A normal mouse, when introduced to another mouse, shows a lot of interest the first time they meet. If the mice are separated then reintroduced, their interest drops because they remember having met before, a phenomenon the researchers call habituation. If they then introduce a completely different mouse, interest piques again at the newbie.

The researchers introduced mice lacking BACE1 to another mouse. The first time they met, the BACE1 mouse showed interest, the second time meeting the same mouse the BACE1 mouse showed less interest and even less interest the third time. The researchers then introduced the BACE1 mouse to a totally different mouse of a different strain and the BACE1 mouse showed no interest at all. “These mice were totally disinterested, normal mice just don’t behave like this,” says Savonenko.

Additionally, the researchers found that these BACE1-lacking mice also displayed many other schizophrenia-like traits. Most importantly, according to Savonenko, some of the deficits improved after treatment with the antipsychotic drug clozapine.

Because schizophrenia is a disorder likely caused by many different factors, Savonenko explains that BACE1 might contribute to an increased risk of schizophrenia in certain patients and the BACE1 mice will be a useful animal model. “We never thought we would see one mouse that closely mimics so many of the clinical features of schizophrenia,” says Alena Savonenko, M.D., Ph.D., an assistant professor of neuropathology at Hopkins. “This could be a really useful model to study and understand the molecular contributions to the disease.”

Source: Johns Hopkins Medical Institutions

Related stories:

Potential Alzheimer's disease drug target identified
In findings with the potential to provide a therapy for Alzheimer’s disease patients where none now exist, a researcher at the University of California, San Diego and colleagues have demonstrated in mice a way to reduce the overproduction of a peptide associated with the disease. The study, which showed substantial improvement in memory in an animal model of Alzheimer’s disease, was led by Vivian Y. H. Hook, Ph.D., professor of the Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, together with American Life Science Pharmaceuticals of San Diego.
Scientists dig deeper into the genetics of schizophrenia by evaluating microRNAs
Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.
Suspected cause of type 1 diabetes caught 'red-handed' for the first time
Scientists at Washington University School of Medicine in St. Louis working with diabetic mice have examined in unprecedented detail the immune cells long thought to be responsible for type 1 diabetes.
Study suggests caution on a new anti-obesity drug in children
A new class of anti-obesity drugs that suppresses appetite by blocking cannabinoid receptors in the brain could also suppress the adaptive rewiring of the brain necessary for neural development in children, studies with mice have indicated. One such drug, rimonabant (trade name Acomplia) has been developed by Sanofi-Aventis and is awaiting approval for use in the U.S., and other pharmaceutical companies are developing similar drugs.
Researchers target tumors with tiny 'nanoworms'
Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors.
Study in mice suggests molecules in plants have beneficial effect on Alzheimer's disease
A set of molecules found in certain plants appears to have a beneficial effect in brain tissue associated with Alzheimer’s disease, according to a new study conducted in mice. The study was led by researchers at the University of South Florida and Cedars-Sinai Medical Center. An article in the Journal of Cellular and Molecular Medicine is available online.
New target for Alzheimer's disease identified
Alzheimer’s disease (AD) is an incurable disease that is increasing in prevalence and will increase even more rapidly as the Baby Boom generation enters the age of highest risk. The available AD drugs are only partially effective in some patients. New strategies are urgently needed.
Killer competition: Neurons duke it out for survival
The developing nervous system makes far more nerve cells than are needed to ensure target organs and tissues are properly connected to the nervous system. As nerves connect to target organs, they somehow compete with each other resulting in some living and some dying. Now, using a combination of computer modeling and molecular biology, neuroscientists at Johns Hopkins have discovered how the target tissue helps newly connected peripheral nerve cells strengthen their connections and kill neighboring nerves. The study was published in the April 18th issue of Science.

News discussion:

Medicine & Health news