Presynaptic regulation of neurotransmitter release in the cortex of aged rats with differential memory impairments.
Cluster analysis of water-maze reference-memory performances of 25-27-month-old (compared to 3-5-month-old) rats distinguished subpopulations of young adult rats (YOUNG), aged rats with no significant impairment (AU), aged rats with moderate impairment (AMI), and aged rats with severe impairment (ASI). In the frontoparietal cortex, we subsequently assessed the electrically evoked release of tritium in slices preloaded with [3H]choline, [3H]noradrenaline (NA), or [3H]serotonin (5-HT) and the effects of an agonist (oxotremorine, UK 14,304, and CP 93,129) of the respective autoreceptors. Cholinergic and monoaminergic markers were measured in homogenates. Overall, aged rats exhibited reduced accumulation of [3H]choline (-25%) and weaker evoked transmitter release (in % of accumulated tritium: -44%, -20%, and -34%, for [3H]acetylcholine, [3H]NA, and [3H]5-HT, respectively). In all rats, the inhibitory effects of the autoreceptor agonists on the evoked release of [3H] were comparable. Acetylcholinesterase (AChE), not choline acetyltransferase (ChAT), activity was reduced. The results suggest age-related modifications in the cholinergic, noradrenergic, and serotonergic innervation of the frontoparietal cortex, alterations of evoked transmitter release, but no interference with presynaptic autoinhibition of the release. Neither of these alterations seemed to account for the cognitive impairment assessed.
Birthelmer
A
A
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse 9A, D-79104 Freiburg, Germany.
Lazaris
A
A
Schweizer
T
T
Jackisch
R
R
Cassel
J-C
JC
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000068438:Brimonidine Tartrate; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D005260:Female; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017661:Receptors, Presynaptic / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents; D011725:Pyridines; D011758:Pyrroles; D011810:Quinoxalines; D017661:Receptors, Presynaptic; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D000068438:Brimonidine Tartrate; D010095:Oxotremorine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine; D009638:Norepinephrine