We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

LabMedica

Download Mobile App
Recent News Expo Clinical Chem. Molecular Diagnostics Hematology Immunology Microbiology Pathology Technology Industry Focus

Glutamate Modulator Reverses Genetic Expressions of Aging and Alzheimer's Diease in Rodent Model

By LabMedica International staff writers
Posted on 16 May 2016
Neurological disease researchers have found that the glutamate modulator riluzole reversed gene expression profiles caused by age and Alzheimer’s disease (AD) in a rat AD model.

Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors. In the opposing postsynaptic cell, glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, glutamate is involved in cognitive functions such as learning and memory in the brain.

Image: After treatment with riluzole, the brains of old rats showed more of a transporter molecule that removes excess glutamate, (green fluorescence, right) as compared to untreated rats (left) (Photo courtesy of The Rockefeller University).
Image: After treatment with riluzole, the brains of old rats showed more of a transporter molecule that removes excess glutamate, (green fluorescence, right) as compared to untreated rats (left) (Photo courtesy of The Rockefeller University).

AD and age-related cognitive decline involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, investigators at the Rockefeller University (New York, NY, USA) characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq) and then validated the expression changes using qRT–PCR open arrays.

The investigators reported in the March 29, 2016, online edition of the journal Molecular Psychiatry that the glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes. Riluzole was known to increase the ability of the glutamate transporter EAAT2 (excitatory amino-acid transporter 2) to scavenge excess glutamate, regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an increase in EAAT2 expression in the hippocampus after riluzole treatment, identifying a possible mechanism underlying the improved memory function.

"In aging and Alzheimer's, the chemical signal glutamate can accumulate between neurons, damaging the circuitry," said first author Dr. Ana Pereira, instructor in clinical medicine at the Rockefeller University. "When we treated rats with riluzole, we saw a suite of changes. Perhaps most significantly, expression of molecules responsible for clearing excess glutamate returned to more youthful levels. We hope to use a medication to break the cycle of toxicity by which glutamate can damage the neurons that use it as a neurotransmitter, and our studies so far suggest that riluzole may be able to accomplish this. We found that in addition to recovering the expression of EAAT2, the drug restored genes critical for neural communication and plasticity, both of which decline with aging and even more significantly in Alzheimer's disease."

Related Links:
Rockefeller University



New
Gold Member
Serological Pipet Controller
PIPETBOY GENIUS
Unit-Dose Packaging solution
HLX
New
Gold Member
ANA & ENA Screening Assays
ANA and ENA Assays
New
Human Immunodeficiency Virus Assay
RealLine HIV Quantitative Kit

Latest BioResearch News

Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns

Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma

New Method Simplifies Preparation of Tumor Genomic DNA Libraries