Rivastigmine as a modulator of the neuronal glutamate transporter rEAAC1 mRNA expression.
Alzheimer's disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.
Andin
Josefine
J
Department of Neuroscience and Locomotion, Division of Geriatric Medicine, Linkopings Universitet Hospital, SE-581 85 Linkoping, Sweden. josefine.andin@inr.liu.se
Enz
Albert
A
Gentsch
Conrad
C
Marcusson
Jan
J
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000235:genetics*; D027322:Amino Acid Transport System X-AG / Q000235:genetics*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D050491:Glutamate Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D019579:Neocortex / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D000068836:Rivastigmine; D027981:Symporters / Q000235:genetics*
D027322:Amino Acid Transport System X-AG; D002800:Cholinesterase Inhibitors; D050491:Glutamate Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D012333:RNA, Messenger; D027981:Symporters; D000068836:Rivastigmine