Featured Research

from universities, journals, and other organizations

How Epilepsy Develops: New Relationship Between Brain Derived Neurotrophic Factor And Inflammatory Signaling

Date:
October 27, 2008
Source:
Boston University
Summary:
The development of epilepsy in adult rats is linked to functional changes in the expression of alpha 1 containing GABA-A receptors.

In the October 14th edition of Science Signaling researchers at Boston University School of Medicine (BUSM), The Children's Hospital of Philadelphia/University of Pennsylvania School of Medicine and The University of Colorado Denver School of Medicine have shown that the development of epilepsy in adult rats is linked to functional changes in the expression of alpha 1 containing GABA-A receptors, the main inhibitory neurotransmitter receptor in the brain, that may be dependent upon BDNF-induced activation of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway.

Related Articles


Activation of the JAK/STAT pathway has previously been shown to be dependent upon cytokines and is implicated in a large number of inflammatory diseases.

The multiple subunits of the GABA-A receptor show developmental and region specific expression in the brain and produce a diverse set of functional receptor isoforms. Drs. Shelley Russek, a molecular neuroscientist/pharmacologist from Boston University School of Medicine and Dr. Amy Brooks-Kayal, a pediatric neurologist researcher from the University of Colorado Denver School of Medicine, believe that changes in inhibitory receptors in a portion of the brain known as the dentate gyrus may be crtically important to the development of temporal lobe epilepsy, the most common type of epilepsy in children and adults. Decrease of GABA-A receptors containing alpha 1 subunits at the synapse, and increase of receptors containing alpha 4, has been associated with spontaneous seizures.

The senior authors recent publication associates the marked rise in BDNF that accompanies prolonged seizures with a specific decrease in the levels of alpha 1 that is reversed upon in vivo delivery of a JAK/STAT pathway inhibitor. Alpha 1 gene regulation is dependent upon the induction of a transcriptional repressor called inducible cAMP early repressor (ICER) that binds to the alpha 1 gene in coordination with the cAMP regulatory element binding protein (CREB).

Previous research from the laboratories of Russek and Brooks-Kayal reported that BDNF increases the abundance of the alpha 4 subunit of the GABA-A receptor independent of JAK/STAT signaling and dependent upon mitogen activating protein kinases (MAPKs). Taken together with the latest results, BDNF acts through at least two distinct pathways to influence GABA-mediated inhibition in the brain. "Our identification of signaling pathways regulating the most abundant form of synaptic GABA-A receptors in the central nervous system may lead to the development of novel molecular therapies for multiple disorders including epilepsy, given that changes in their expression are also associated with alcoholism, anxiety and stress," states Dr. Russek.

An estimated 400,000 Americans have temporal lobe epilepsy – a neurological impairment that includes both psychopathology and altered brain physiology. Onset of this form of epilepsy in some adults and children can be linked to an initial brain injury or systemic infection. However multiple cases are without such associations and are not treatable by traditional medical therapies.

The National Institutes of Health and the American Epilepsy Society provide grant support that funds the Russek and Brooks-Kayal collaborative research effort.


Story Source:

The above story is based on materials provided by Boston University. Note: Materials may be edited for content and length.


Cite This Page:

Boston University. "How Epilepsy Develops: New Relationship Between Brain Derived Neurotrophic Factor And Inflammatory Signaling." ScienceDaily. ScienceDaily, 27 October 2008. <www.sciencedaily.com/releases/2008/10/081022142948.htm>.
Boston University. (2008, October 27). How Epilepsy Develops: New Relationship Between Brain Derived Neurotrophic Factor And Inflammatory Signaling. ScienceDaily. Retrieved February 26, 2015 from www.sciencedaily.com/releases/2008/10/081022142948.htm
Boston University. "How Epilepsy Develops: New Relationship Between Brain Derived Neurotrophic Factor And Inflammatory Signaling." ScienceDaily. www.sciencedaily.com/releases/2008/10/081022142948.htm (accessed February 26, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, February 26, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sleeping Too Much Or Too Little Might Increase Stroke Risk

Sleeping Too Much Or Too Little Might Increase Stroke Risk

Newsy (Feb. 26, 2015) People who sleep more than eight hours per night are 45 percent more likely to have a stroke, according to a University of Cambridge study. Video provided by Newsy
Powered by NewsLook.com
London Show Dissects History of Forensic Science

London Show Dissects History of Forensic Science

AFP (Feb. 25, 2015) Forensic science, which has fascinated generations with its unravelling of gruesome crime mysteries, is being put under the microscope in an exhibition of real criminal investigations in London. Duration: 00:53 Video provided by AFP
Powered by NewsLook.com
Michigan Couple Celebrates Identical Triplets

Michigan Couple Celebrates Identical Triplets

AP (Feb. 25, 2015) A suburban Detroit couple who have two older children are adjusting to life after becoming parents to identical triplets _ a multiple birth a doctor calls rare. (Feb. 25) Video provided by AP
Powered by NewsLook.com
Mayor Says District of Columbia to Go Ahead With Pot Legalization

Mayor Says District of Columbia to Go Ahead With Pot Legalization

Reuters - News Video Online (Feb. 25, 2015) Washington&apos;s mayor says the District of Columbia will move forward with marijuana legalization, despite pushback from Congress. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins