Researchers discover new link to schizophrenia

May 8, 2008

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

Explore further: PET tracer gauges effectiveness of promising Alzheimer's treatment

Related Stories

PET tracer gauges effectiveness of promising Alzheimer's treatment

December 6, 2017
In the December featured basic science article in The Journal of Nuclear Medicine, Belgian researchers report on the first large-scale longitudinal imaging study to evaluate BACE1 inhibition with micro-PET in mouse models ...

Poor recycling of BACE1 enzyme could promote Alzheimer's disease

November 21, 2011
Sluggish recycling of a protein-slicing enzyme could promote Alzheimer's disease, according to a study published online on November 21 in The Journal of Cell Biology.

Brain enzyme is double whammy for Alzheimer's disease

August 20, 2012
The underlying causes of Alzheimer's disease are not fully understood, but a good deal of evidence points to the accumulation of β-amyloid, a protein that's toxic to nerve cells. β-amyloid is formed by the activity ...

New study finds how a single brain trauma may lead to Alzheimer's disease

July 24, 2012
A study, performed in mice and utilizing post-mortem samples of brains from patients with Alzheimer's disease, found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate ...

Scientists reveal role for lysosome transport in Alzheimer's disease progression

August 7, 2017
Researchers from Yale University School of Medicine have discovered that defects in the transport of lysosomes within neurons promote the buildup of protein aggregates in the brains of mice with Alzheimer's disease. The study, ...

Recommended for you

Fresh approach to tuberculosis vaccine offers better protection

January 17, 2018
A unique platform that resulted in a promising HIV vaccine has also led to a new, highly effective vaccine against tuberculosis that is moving toward testing in humans.

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

New study validates clotting risk factors in chronic kidney disease

January 17, 2018
In late 2017, researchers from Boston University School of Medicine (BUSM) discovered and published (Science Translational Medicine, (9) 417, Nov 2017) a potential treatment target to prevent chronic kidney disease (CKD) ...

Newly-discovered TB blood signal provides early warning for at-risk patients

January 17, 2018
Tuberculosis can be detected in people with HIV infection via a unique blood signal before symptoms appear, according to a new study by researchers from the Crick, Imperial College London and the University of Cape Town.

New study offers insights on genetic indicators of COPD risk

January 16, 2018
Researchers have discovered that genetic variations in the anatomy of the lungs could serve as indicators to help identify people who have low, but stable, lung function early in life, and those who are particularly at risk ...

Previous influenza virus exposures enhance susceptibility in another influenza pandemic

January 16, 2018
While past exposure to influenza A viruses often builds immunity to similar, and sometimes different, strains of the virus, Canadian researchers are calling for more attention to exceptions to that rule.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.