title: Effect of treatment with the cholinesterase inhibitor rivastigmine on vesicular acetylcholine transporter and choline acetyltransferase in rat brain.
abstract: A decline of cholinergic neurotransmission probably contributes to cognitive dysfunction occurring in Alzheimer's disease (AD) and vascular dementia (VaD). Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors are the only drugs authorized for symptomatic treatment of AD and are also under investigation for VaD. The present study has investigated the influence of two doses of the AChE inhibitor rivastigmine (0.625 mg/Kg/day and 2.5 mg/Kg/day) on vesicular acetylcholine transporter (VAChT) and on choline acetyltransferase (ChAT) expression in frontal cortex, hippocampus, striatum and cerebellum of normotensive and spontaneously hypertensive rats (SHR). Cholinergic markers were assessed by immunochemical (Western blotting) and immunohistochemical techniques. In frontal cortex and striatum of normotensive rats, treatment with the lower dose (0.625 mg/Kg/day) of rivastigmine had no effect on VAChT immunoreactivity and increased slightly ChAT protein immunoreactivity. The higher dose (2.5 mg/Kg/day) of the compound increased significantly VAChT and ChAT protein immunoreactivity. In hippocampus rivastigmine induced a concentration-dependent increase of VAChT protein expression and no significant changes of ChAT protein expression. A similar pattern of VAChT and ChAT protein expression was observed in control SHR, whereas treatment of SHR with rivastigmine induced a more pronounced increase of VAChT protein immunoreactivity in frontal cortex, hippocampus and striatum compared to normotensive rats. Our data showing an increase of VAChT after treatment with rivastgmine further support the notion of an enhancement of cholinergic neurotransmission by AChE/ChE inhibitors. The observation of a greater expression of this cholinergic marker in SHR suggest that AChE inhibition may provide beneficial effects on cholinergic neurotransmission in an animal model of VaD.
authors.affiliation: Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Camerino, Italy. khosrow.tayebati@unicam.it
authors.forename: Seyed Khosrow
authors.initials: SK
authors.lastname: Tayebati
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Di Tullio
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D015140:Dementia, Vascular / Q000188:drug therapy / Q000209:etiology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D026901:Membrane Transport Proteins; D048448:Phenylcarbamates; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000068836:Rivastigmine; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D026901:Membrane Transport Proteins; D048448:Phenylcarbamates; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D002795:Choline O-Acetyltransferase; D000068836:Rivastigmine