Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Knowing how ketamine impairs brain circuitry may lead to new therapies for schizophrenia

10.12.2007
Scientists know that the drug ketamine – street name “Special K” – can induce schizophrenia-like symptoms in drug abusers.

Ketamine is also used as an anesthetic and, more recently, as an antidepressant – raising concerns by researchers at the University of California, San Diego (UCSD) School of Medicine, who have found that ketamine leads to the impairments in brain circuitry observed in both drug abusers and schizophrenic patients by causing increased production of a toxic free radical called “superoxide.” Their findings, which could point the way to novel treatments for schizophrenia, will be published in the December 7 issue of the journal Science.

A research team led by Laura Dugan, M.D., Larry L. Hillblom Professor of Geriatrics and research scholar with the UCSD Stein Institute for Research on Aging, discovered an unexpected link between the inflammatory enzyme complex NADPH oxidase and the dysfunction of certain brain neurons exposed to ketamine. NADPH oxidase is normally found in white blood cells circulating outside the brain, where it helps kill bacterial and fungal infections by producing superoxide, a compound that can cause substantial damage to cells.

“Because of NADPH oxidase’s protective role in fighting infection, it was very surprising to find that the complex wears a second hat – it is also critical for modulating signaling in the brain,” said first author M. Margarita Behrens, Ph.D., Division of Geriatric Medicine, UCSD School of Medicine.

... more about:
»NADPH »Oxidase »UCSD »circuitry »ketamine »neurons »schizophrenia

According to Behrens, it was known that ketamine initially impairs the inhibitory circuitry in the brain’s cortex and hippocampus by blocking the NMDA receptor, a molecule on the cell surface that controls the activity of neurons. But the UCSD researchers discovered that, as a result of blocking the receptor, ketamine also substantially increased the activity of NADPH oxidase, causing further disruption of neuronal signaling.

“Ketamine causes a ‘disinhibition’ of brain circuitry, taking the brakes off the system and causing overexcitation of the brain in response to a stimulus,” said Behrens. “This overexcitation activates NADPH oxidase, which then produces superoxide – resulting in detrimental changes in key synaptic proteins and profoundly affecting nervous system function.”

The result is impairment of the brain circuitry involved in memory, attention and other key functions related to learning. Loss of such functions sets up individuals for psychosis and deficits in information processing, resulting in symptoms such as hallucinations and delusions, as well as social withdrawal and cognitive problems, according to Behrens.

Using ketamine, Behrens and Dugan mimicked features of schizophrenia in mice, and then analyzed neurons in a region of the mouse brain that corresponds to the prefrontal cortex in humans where profound changes occur in patients with schizophrenia. The researchers found a substantial increase in the activity of NADPH oxidase, and that this activity made some neurons in this inhibitory circuitry “disappear.” When the researchers blocked the activity of NADPH oxidase with an inhibitor, or with a compound that annihilates superoxide, these neurons were protected.

“Our findings suggest that compounds that inhibit NADPH oxidase in the brain, without totally blocking its protective function of killing bacteria, could provide future therapies for schizophrenia or other diseases in humans that exhibit similar changes in neural circuitry,” said Behrens.

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

Further reports about: NADPH Oxidase UCSD circuitry ketamine neurons schizophrenia

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>