Navigation Links
A new relationship between brain derived neurotrophic factor and inflammatory signaling
Date:10/22/2008

(Boston)-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. 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.


'/>"/>

Contact: Gina Digravio
gina.digravio@bmc.org
617-638-8491
Boston University
Source:Eurekalert

Related medicine news :

1. Anger Could Ruin Your Relationship
2. Study examines relationship between low birth weight and psychiatric problems in children
3. Charities take note: Personal relationships increase donations
4. Perceived level of intimacy within a relationship predicts relational uncertainty
5. Gold Medalist Jennie Finch & Relationship Expert Stacy Kaiser Help Wired Couples Unplug
6. Cardinal Health Expands Leader(R) Offering To Help Independent Pharmacies Strengthen Patient Relationships, Solidify Role As Local Health Care Experts
7. Bill Fergusons New Book, Get Your Power Back: It Only Takes One Person to Heal a Difficult Relationship
8. Psychologist poses new hand-eye relationship
9. The Henry H. Kessler Foundation Appoints New Vice President for Research and Strengthens Relationship With Current Research Luminary
10. Relationship Violence Common Among College Students
11. Author & Radio Host Tim Kellis Charges Psychologists Who Write Relationship Books are Helping to Spawn a Divorce Industry
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/23/2017)... ... January 23, 2017 , ... The iaedp Foundation, recognized ... treatment providers who treat the full spectrum of eating disorder problems, proudly announces ... Council consists of the leading eating disorder treatments centers located throughout the U.S. ...
(Date:1/23/2017)... ... ... Sharon Kleyne, America’s leading water researcher, advocate and feared enemy of dry ... new water infrastructure a number one priority. “As we usher in a new national ... become a top priority of our new political change agents.” Kleyne pointed out that ...
(Date:1/23/2017)... ... January 23, 2017 , ... METTLER TOLEDO has ... Chemistry by Applying Simple PAT Tools . , Crystallization is a ... the desired product. Chemists now spend more time developing better intermediate and ...
(Date:1/23/2017)... , ... January 23, 2017 , ... "ProRandom is a set of camera tools that ... dynamic looks in Final Cut Pro X," said Christina Austin - CEO of Pixel Film ... two layers of text with video footage. ProRandom works by using a virtual camera ...
(Date:1/23/2017)... ... 23, 2017 , ... Gynecology Associates of Gwinnett (GAoG) has ... for women of all ages. The staff of Gynecology Associates of Gwinnett ... from routine health screenings to diagnosing and treating female concerns including menopause, urinary ...
Breaking Medicine News(10 mins):
(Date:1/23/2017)... Jan. 23, 2017  Delcath Systems, Inc. (NASDAQ: ... the treatment of primary and metastatic liver cancers, today ... CRNP, President and Chief Executive Officer of Delcath will ... Capital Markets, Thirteenth Annual Investor Conference at the Boca ... Florida , on Tuesday, January 31, 2017 at ...
(Date:1/23/2017)... , January 23, 2017 ... (r enal) y el riesgo ... de a pabetalone    Resverlogix Corp. ... resultados preliminares de un ensayo en fase 1 con ... de riñón (renal) severa. Los datos demostraron unos resultados ...
(Date:1/23/2017)... The global  anxiety disorders and depression treatment market  is expected to reach ... worldwide is anticipated to drive the market growth in the coming years. Increasing ... in the recent years. Continue Reading ... ... ...
Breaking Medicine Technology: