Navigation Links
Engineered mouse mimics cognitive aspects of schizophrenia

Researchers have developed a mouse strain in which the abnormal activity of the dopamine machinery in a specific part of the brain causes cognitive and behavioral impairments mimicking those in human schizophrenics.

The achievement is important, because creating an animal model of any schizophrenic characteristics has not been done before. And schizophrenia's genetic and physiological complexities have seriously hindered efforts to understand the disorder.

Dr.s Christoph Kellendonk, Eleanor H. Simpson, Eric R. Kandel and colleagues reported their development of the mouse model in an article in the February 16, 2006, issue of Neuron.

In a preview of the study in the same issue of Neuron, neuroscientist Solomon Snyder wrote that the researchers' findings--along with studies implicating specific genes in schizophrenia--"afford a basis for optimism" that the engineered mice could provide an animal model for schizophrenia. "In this case, the transgenic mice developed by Kellendonk and colleagues may provide a valuable tool for understanding this most malignant of mental disorders," wrote Snyder.

Kellendonk and his colleagues based their experiments on a widely accepted theory that hyperactivity in the brain's dopamine machinery plays a central role in schizophrenia. Dopamine is a major neurotransmitter in the brain--a chemical messenger that one neuron launches at its neighbor to trigger a nerve impulse in the receiving neuron.

The major antipsychotic drugs are believed to "dial down" the dopamine machinery by blocking receptors for dopamine on the surface of neurons. Also, amphetamines, which release dopamine, are known to aggravate schizophrenic symptoms.

The researchers also based their experiments on evidence that abnormalities in the brain region known as the striatum can affect cognitive function in schizophrenics--by indirectly influencing the prefrontal cortex, a major center for cognitive function.

To mimic the hyperactive dopamine machinery, the researchers created a genetically altered mouse strain in which dopamine receptors were overexpressed only in the striatum. What's more, they engineered the mouse strain so that they could shut down this overexpression by giving the mice the antibiotic doxycycline.

The researchers found that the engineered animals showed no difference from normal mice in their general cognitive functioning, activity level, sensorimotor functioning, or anxiety.

However, the mice did show the same kinds of specific cognitive deficits seen in human schizophrenics. In tests using mazes, the animals showed deficits in "working memory"--the temporary storage of information required for a task. The animals also showed poorer behavioral flexibility; they were less able than normal mice to reverse their association of a particular odor with a reward.

Biochemical analyses of the animals' brains revealed that the excess dopamine receptor activity in the striatum contributed to abnormal prefrontal cortical function.

Importantly, found the researchers, they could not reverse these cognitive deficits by using the antibiotic to damp down the dopamine machinery. This finding suggests that the effect of the abnormal dopamine machinery was developmental, they said.

"If increased activation of [dopamine] receptors indeed contributes to the cognitive deficits of patients with schizophrenia, our data could explain why antipsychotics do not greatly ameliorate cognitive deficits," wrote the researchers. "The physiological alterations that are responsible for cognitive deficits may be present long before the first psychotic episode, when treatment usually commences. Thus, treatment with typical antipsychotics may be too late to reverse the physiological alterations that are responsible for the cognitive deficits."

The researchers cautioned that "Rodent models of schizophrenia have significant limitations. The neuronal circuits affected in people are more complex than the analogous circuits in rodents. In particular, the relative size of the prefrontal cortex that is involved in the cognitive deficits is much smaller in rodents than in primates. Some of the cognitive symptoms such as hallucinations or delusions are impossible to address.

"However, rodent models have the advantage of allowing direct tests of cause-effect relationships for specific aspects of the disease, such as some of the cognitive deficits," they concluded. "We here have been able to introduce genetically a single molecular alteration in a restricted and regulated fashion and to study its behavioral and physiological consequences."

The researchers said that their findings suggest that cognitive symptoms of schizophrenia may arise from subtle genetic differences in the dopamine receptor gene in schizophrenics that increase receptor activity.


'"/>

Source:Cell Press


Related biology news :

1. Engineered molecule amplifies bodys immune response
2. Engineered skin offers clues to melanoma development
3. Engineered Stem Cells Show Promise For Sneaking Drugs Into The Brain
4. Engineered heart tissue offers insights into irregular heartbeats, defibrillator failure
5. Engineered yeast speeds ethanol production
6. Man and mouse share genome structures
7. Genome-wide mouse study yields link to human leukemia
8. Report that delayed motherhood decreases life expectancy of mouse offspring
9. Agilent Technologies introduces advanced zebrafish, mouse microarrays for stem cell and developmental biology research
10. Stem cells in bone marrow replenish mouse ovaries
11. Mosaic mouse technique offers a powerful new tool to study diseases and genetics
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/8/2017)... About Voice Recognition Biometrics Voice recognition biometrics ... a stored voiceprint template. Acoustic features of an ... are compared to distinguish between individual voices. Voice ... PCs already have a microphone and can authenticate ... are most likely to be deployed in telephone-based ...
(Date:2/8/2017)... 2017 Report Highlights The global ... $8.3 billion in 2016 at a compound annual growth ... Report Includes - An overview of the global market ... data from 2015 and 2016, and projections of compound ... the market on the basis of product type, source, ...
(Date:2/6/2017)... 2017 According to Acuity Market Intelligence, ... authorities to continue to embrace biometric and digital ... Automated Border Control (ABC) eGates and 1436 Automated ... than 163 ports of entry across the globe. ... a combined CAGR of 37%. APC Kiosks reached ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... Fort Washington, PA (PRWEB) , ... ... ... The Omnia-Prova Education Collaborative (TOPEC), the leading medical education provider of ... Accreditation with Commendation by the Accreditation Council for Continuing Medical Education (ACCME). ...
(Date:2/22/2017)... Dublin - Research ... Crop Protection (Bio-Pesticide) Market-By Type, By Application, By End User, By ... offering. ... Biological Crop Protection Market is forecasted to grow at a CAGR ... biopesticide or biological crop protection market is driven by the surging ...
(Date:2/22/2017)... ... February 22, 2017 , ... Pharma and biotech ... as European director. Operating from Pennside’s Zurich headquarters, Pennside Partners, GmbH, Mr. Perkins ... Pennside after more than a decade with leading market research firm, GfK. He ...
(Date:2/21/2017)... - SQI Diagnostics Inc. ("SQI" or the "Company") (TSX-V: SQD; OTCQX: ... months ended December 31, 2016. SQI is ... company that develops and commercializes proprietary technologies and products for ... ... milestones achieved in fiscal 2016," said Andrew Morris , ...
Breaking Biology Technology: