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:3/24/2017)... ... March 24, 2017 , ... The Radiology Business Management Association (RBMA) ... annual awards, now in their 12th year, are among the most prestigious in radiology ... 2016, the awards were retooled to recognize achievements in both large budget (over $5,000) ...
(Date:3/24/2017)... Arizona (PRWEB) , ... March 24, 2017 , ... ... Healing Center, Sedona, Arizona’s Premier Center for Shamanic Healing and Spiritual Awakening, ... Luis Delgado, June 9--24, 2017. This sacred and spiritual journey during the ...
(Date:3/24/2017)... ... ... The law firm of Enea, Scanlan & Sirignano, LLP, with ... C. Enea has joined the firm as an associate attorney. Ms. Enea, who previously ... law, Medicaid planning and applications, and Wills, Trusts and Estates. Samantha A. Lyons, ...
(Date:3/24/2017)... ... March 24, 2017 , ... “Finding Christ Through Social ... devotional journal chronicling the writer’s path toward true communion with God. “Finding Christ ... #TruthwithGrace” is the creation of published author Lea Michelle Johnson, a follower of ...
(Date:3/23/2017)... ... March 23, 2017 , ... In 2016 the World Health Organization ... could be four million Zika-related cases in the Americas within the next year. Lyme ... cases reported per year skyrocketing to an estimated 329,000. Yet, Zika, Lyme and other ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... YORK , March 24, 2017 ... ... a leading publisher of cannabis market research, the legal cannabis ... percent CAGR through 2021, despite conflicting signals from the current ... points out that the two biggest drivers of growth in ...
(Date:3/24/2017)... Research and Markets has announced the addition of the ... report to their offering. ... The Deep Learning: Drug Discovery and Diagnostics Market, 2017-2035 ... market of deep learning solutions within the healthcare domain. Primarily driven ... a novel solution to generate relevant insights from medical data. ...
(Date:3/24/2017)... -- Today Stock-Callers.com have issued research reports on ... (NASDAQ: NVCN), Hologic Inc. (NASDAQ: HOLX), Edwards Lifesciences Corp. (NYSE: ... These companies are part of the Healthcare sector, which gave ... rd , 2017, with the NYSE Health Care Index declining ... in the S&P 500 were down about 0.4% as a ...
Breaking Medicine Technology: