K. Mercer

Bio: K. Mercer is an academic researcher from University of Nottingham. The author has contributed to research in topics: High-performance liquid chromatography & Neurofibrillary tangle. The author has an hindex of 2, co-authored 3 publications receiving 39 citations.

Electrochemical detection of human brain transmitter amino acids by high-performance liquid chromatography of stable o-phthalaldehyde-sulphite derivatives.

Abstract: A simple, sensitive, reliable and reproducible isocratic HPLC technique for the measurement of OPA/sulphite derivatives of human brain amino acid neurotransmitters is described. This employs a sample preparation that is also compatible with the concurrent determination of monoamines and their metabolites on a separate HPLC system. The method has been applied to the determination of GABA and glutamate in brain tissue taken post-mortem from patients with Huntington's disease and control subjects.

Alzheimer-like changes of cortical amino acid transmitters in elderly Down’s syndrome

Abstract: The concentrations of glutamate and GABA were determined in samples of frontal and temporal cortex and hippocampus taken post mortem from nine patients with Down’s syndrome and nine control subjects. These results were correlated with neuropathological findings and compared to changes found in patients with Alzheimer’s disease. GABA demonstrated an Alzheimer-like reduction in the temporal cortex and hippocampus, although this was not found in the frontal cortex. These deficits correlated with cell density but not plaque or tangle counts. Glutamate was significantly reduced only in the hippocampus, but found not to be changed in Alzheimer’s disease.

Adenosine A2a Receptor‐Mediated Modulation of Striatal [3H]GABA and [3H]Acetylcholine Release

Abstract: The ability of adenosine agonists to modulate K+-evoked 4D†-[3H]aminobutyric acid ([3H]GABA) and acetylcholine (ACh) release from rat striatal synaptosomes was investigated. The A2a receptor-selective agonist CGS 21680 inhibited Ca2+-dependent [3H]GABA release evoked by 15 mM KCI with a maximal inhibition of 29 ± 4% (IC50 of ∼4 ± 10 −12M). The relative order of potency of three agonists was CGS 21680 ± 5′-N-ethylcarboxamidoadenosine > R-phenylisopropyladenosine (R-PIA), with the inhibition being blocked by A2a receptor-selective antagonists (CP 66,713 and CGS 15943A) but not by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). When release of [3H]GABA was evoked by 30 mM KCI, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [3H]ACh evoked by 30 mM KCI, with a maximal stimulation of 26 ± 5% (IC50 of ∼10−11M). This effect was blocked by CP 66,713 but not by DPCPX. The A1 agonist R-PIA inhibited [3H]ACh release, an effect blocked by DPCPX. It is concluded that adenosine A2a receptors are present on both GABAergic and cholinergic striatal nerve terminals where they inhibit and stimulate transmitter release, respectively. Key Words: GABA—Acetylcholine—Adenosine receptors—Striatum.

Low cumulative manganese exposure affects striatal GABA but not dopamine

Abstract: The introduction of the anti-knock methylcyclopentadienyl manganese (Mn) tricarbonyl (MMT) in gasoline has raised concerns about the potential for manganese neurotoxicity. Because subpopulations such as the elderly in the early stages of neurodegenerative disease may be at increased risk for manganese toxicity, a pre-Parkinsonism rat model was used to evaluate whether sub-chronic manganese exposure can aggravate the neurochemical and behavioral dysfunctions characteristic of Parkinsonism. Sub-threshold levels of dopamine depletion of 3.5, 53 and 68% were generated via intrastriatal unilateral 6-hydroxydopamine (6-OHDA) doses. A sub-chronic dosing regimen of low cumulative manganese exposure (4.8 mg Mn/kg body weight, 3 i.p. injections per week x 5 weeks) was started 4 weeks after 6-OHDA treatments. Neurochemical and neuromotor (functional observational battery (FOB)) measures were evaluated. Manganese produced significant (P < 0.05) reductions of 30-60% in motor function. This effect was exacerbated in the presence of a pre-Parkinsonism condition [Neurotox. Teratol. 22 (2000) 851]. Manganese did not affect striatal dopamine, but resulted in significant increases in striatal y-aminobutyric acid (GABA) of 16 and 22% (P < 0.01) in both striati and a borderline non-significant 4% increase in frontal cortex (P = 0.076). Manganese treatment produced increased aspartate (P < 0.01) in the manganese and 6-OHDA treated striatum. In light of previous studies predominantly showing dopamine depletion with elevated manganese exposures, the significant effects of manganese on striatal GABA but not on striatal dopamine at the low cumulative exposure administered here suggest a progression in manganese toxicity with increasing cumulative dose, whereby GABA levels are adversely affected before striatal dopamine levels. Because these neurochemical disruptions were accompanied by motor dysfunction that was exacerbated in the presence of a pre-Parkinsonism condition, an increased environmental burden of manganese may have deleterious effects on populations with sub-threshold neurodegeneration in the basal ganglia (e.g. pre-Parkinsonism).