Cognitive deficits in aged rats correlate with levels of L-arginine, not with nNOS expression or 3,4-DAP-evoked transmitter release in the frontoparietal cortex.
Aging is associated with altered neurotransmitter function in the brain. In this study, we measured release parameters for acetylcholine (ACh), norepinephrine and serotonin in the frontoparietal cortex of young and aged rats. We also determined cortical amino acid concentrations and nitric oxide (NO) synthase function. Prior to sacrifice, the rats had been tested for Morris water-maze performance. In aged, compared with young rats, we observed a reduction in both uptake of choline and acetylcholine release. Serotonin release and L-arginine concentrations (a precursor of NO) showed an aging-related increase; however, L-citrulline/L-arginine ratios were decreased in aged rats. Moreover, while most age-related changes in transmitter release or neurochemical markers were not related to the learning performance, L-arginine concentrations were positively correlated to cognitive deficits. NO synthase concentrations were not affected by aging. It is suggested that events related to L-arginine-to-L-citrulline/NO metabolism in the frontoparietal cortex may take part in age-related cognitive deficits.
Cassel
Jean-Christophe
JC
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse 9A, D-79104 Freiburg, Germany. jean-christophe.cassel@psycho-ulp.u-strasbg.fr
Schweizer
Theresa
T
Lazaris
Anelise
A
Knörle
Rainer
R
Birthelmer
Anja
A
Gödtel-Armbrust
Ute
U
Förstermann
Ulrich
U
Jackisch
Rolf
R
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000077770:Amifampridine; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D009638:Norepinephrine / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012701:Serotonin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D001120:Arginine; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000109:Acetylcholine; D000077770:Amifampridine; D009638:Norepinephrine