Featured Research

from universities, journals, and other organizations

GABA inverse agonist restores cognitive function in Down's syndrome

Date:
October 7, 2013
Source:
European College of Neuropsychopharmacology (ECNP)
Summary:
A selective GABA inverse agonist has restored cognitive function in a mouse model of Down’s syndrome (DS) and has the potential to benefit humans, French researchers have revealed.

A selective GABA inverse agonist has restored cognitive function in a mouse model of Down's syndrome (DS) and has the potential to benefit humans, French researchers have revealed.

"The drug we used is a specific GABA-A α5 inverse agonist (α5IA) that hypothetically could combat the abnormal neuronal excitation/inhibition balance associated with DS," explained lead researcher Dr Benoit Delatour from the Research Centre of the Institute of Brain and Spinal Cord (Centre de Recherche de l'Institut du Cerveau et de Moelle Epiniθre) at the University Pierre and Marie Curie, Paris.

"We observed that repeated and even single administrations of the α5IA molecule can potentiate learning and memory performances in cognitively-impaired DS mice, underlying the potency of this therapeutic approach," he added.

An imbalance between inhibitory and excitatory neurotransmission has recently been proposed as a factor in the altered brain function of individuals with DS. While several studies have suggested GABA-A antagonists for restoring learning and memory performances in DS mouse models, many tend to cause seizures in animal models as well as in humans.

To investigate safer agents, the researchers used a GABA-A inverse agonist (α5IA) to specifically target the α5 subunit of GABA-A receptors in Ts65Dn mice, a classical animal model of DS.

They found that the drug had no convulsant effects and did not promote any side effects on sensory-motor and anxiety-related behaviours. They also found no evidence of histological changes in various organ tissues following chronic administration.

To investigate what impact α5IA had on learning and memory function, the team trained the mice in a spatial navigation (Morris water maze) task. They found that Ts65Dn mice showed a clear learning impairment that was reversed following daily treatment with α5IA. Furthermore, an acute injection of α5IA before acquisition was enough to alleviate recognition memory impairments in the Ts65Dn mice.

"α5IA enhanced behaviourally-evoked immediate early gene products (as markers of neuronal activation) in specific brain regions and also restored normal levels of gene expression in several disregulated pathways," explained Dr Delatour.

"Such stimulation of neuronal activity and normalisation of gene expression combined with the known effects of α5IA on synaptic plasticity, might support the promnestic [memory enhancing] and therapeutic effects of the drug," he added.

With future human trials planned, Dr Delatour is optimistic about the impact his research could have on cognitive impairment in individuals with DS. "The results obtained by us and by others are very encouraging ... it appears that several targets in DS have been identified and can be the source of new pharmaceutical interventions. It is very likely that the combination of different emerging therapies will provide significant clinical outcomes for people with DS."


Story Source:

The above story is based on materials provided by European College of Neuropsychopharmacology (ECNP). Note: Materials may be edited for content and length.


Cite This Page:

European College of Neuropsychopharmacology (ECNP). "GABA inverse agonist restores cognitive function in Down's syndrome." ScienceDaily. ScienceDaily, 7 October 2013. <www.sciencedaily.com/releases/2013/10/131007094004.htm>.
European College of Neuropsychopharmacology (ECNP). (2013, October 7). GABA inverse agonist restores cognitive function in Down's syndrome. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2013/10/131007094004.htm
European College of Neuropsychopharmacology (ECNP). "GABA inverse agonist restores cognitive function in Down's syndrome." ScienceDaily. www.sciencedaily.com/releases/2013/10/131007094004.htm (accessed October 21, 2014).

Share This



More Mind & Brain News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Your Birth Season Might Determine Your Temperament

Your Birth Season Might Determine Your Temperament

Newsy (Oct. 20, 2014) — A new study says the season you're born in can determine your temperament — and one season has a surprising outcome. Video provided by Newsy
Powered by NewsLook.com
Court Ruling Means Kids' Online Activity Could Be On Parents

Court Ruling Means Kids' Online Activity Could Be On Parents

Newsy (Oct. 17, 2014) — In a ruling attorneys for both sides agreed was a first of its kind, a Georgia appeals court said parents can be held liable for what kids put online. Video provided by Newsy
Powered by NewsLook.com
The Best Foods To Boost Your Mood

The Best Foods To Boost Your Mood

Buzz60 (Oct. 17, 2014) — Feeling down? Reach for the refrigerator, not the medicine cabinet! TC Newman (@PurpleTCNewman) shares some of the best foods to boost your mood. Video provided by Buzz60
Powered by NewsLook.com
You Can Get Addicted To Google Glass, Apparently

You Can Get Addicted To Google Glass, Apparently

Newsy (Oct. 15, 2014) — Researchers claim they’ve diagnosed the first example of the disorder in a 31-year-old U.S. Navy serviceman. Video provided by Newsy
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