Evidence that N-acetylaspartylglutamate is the Astrocyte-Targeted Neurovascular Coupling Agent that Regulates Slow Tonic Control of Brain Blood Flow
Journal Title: Journal of Glycomics and Metabolism - Year 2015, Vol 1, Issue 1
Abstract
N-acetylaspartylglutamate (NAAG) is the highest concentration dipeptide present in brain. It is found primarily in neurons but its function is unclear. NAAG is synthesized by neurons from N-acetylaspartate and glutamate (Glu), maintained at mM concentrations and is released non-synaptically to extracellular fluid (ECF). NAAG is a non-excitatory form of Glu, and is targeted to the metabotropic group II Glu receptor 3 (mGluR3) on the surface of astrocytes. After docking with the receptor, Glu is released by the action of NAAG peptidase. Previously, it was shown for the first time that an NAAG-peptidase inhibitor reduced global cerebral blood flow (CBF) in mouse brain but did not affect their physical performance. Recently, it has been demonstrated that there are two separate systems involved in neurovascular coupling by astrocytes, one is a rapid focal phasic response providing energy for stimulation-induced neuronal activity, and the other a slower global tonic response providing energy for ongoing metabolic activities. Many neurovascular coupling mechanisms are known that regulate phasic changes in CBF, but how the brain accomplishes tonic control is unknown. In this paper we bring together two separate lines of inquiry, the decades’ long search for the function of NAAG, and the more recent search for the mechanism of tonic neurovascular control. Herein, we present evidence that NAAG is the neurovascular coupling agent that regulates tonic changes in CBF via the astrocyte mGluR3-NAAG peptidase connection.
Authors and Affiliations
Morris H Baslow, David N Guilfoyle
Keywords
Related Articles
- EP ID EP261842
- DOI 10.14302/issn.2572-5424.jgm-16-1028
- Views 127
- Downloads 0
Lactic Acidosis : A Poorly Understood Concept
Lactic acidosis is a condition commonly encountered in the hospital setting particularly in critically ill patients and is very often used as a diagnostic adjunct when encountering cases of ischaemia or other hypoperfusi...
Rescuing Canavan Disease by Redirecting Metabolic Processing: Support for the Astrocyte Hypothesis of Canavan Disease Generation and A Possible Human Cure
Canavan disease (CD) is a globally occurring but rare human spongiform leukodystrophy that is associated with inborn errors affecting the activity of aspartoacylase (ASPA), an enzyme highly expressed in oligodendrocytes...
Humans Chromosome 1 Fractal Periods Signature is Highly Correlated with Intelligence and Brain Evolution
DUF1220 proteins regions show the largest Homo-Sapiens lineage-specific increase in copy number of any protein-coding region in the human genome and map principally to 1q21.1. DUF1220 deletions have been associated with...
Synthesis and Assessment of a New Tetrahydrogeraniol Derivative as Penetration Enhancer for Transdermal Drug Delivery
Background: Skin is one the most important sites for administration of drugs to obtain desired pharmacological effects either locally or through systemic bioavailability; and this has placed the transdermal route of dru...
Early Glycine Supplementation Re-Establishes Adrenal Catecholamine Secretion in Hypothalamic Obesity Model in Rats but does not Affect Visceral Adiposity.
Obesity is a worldwide epidemic that features a multifactorial syndrome characterized by a chronic positive energetic unbalance. Neonatal administration of monosodium L-glutamate (MSG) causes lesion on the arcuate nucleu...