Research article summary (published 27 Mar 2007):

Donepezil induces a cholinergic sprouting in basocortical degeneration.

Full Abstract

One of the few currently approved therapies for Alzheimer's disease (AD) consists in the administration of acetylcholinesterase inhibitors, which enhances the lifetime of the neurotransmitter acetylcholine. Despite numerous studies on the symptomatic effect of acetylcholinesterase inhibitors, there is as yet no direct morphological evidence to indicate that they have a neurorestorative action. We investigated the effect of the acetylcholinesterase inhibitor donepezil administered subcutaneously in a rat model of partial unilateral cortical devascularization that induces a loss of the cortical cholinergic terminal network and a retrograde degeneration of the cholinergic projections that originate in the nucleus basalis. For 6 weeks, lesioned and sham-operated rats received a subcutaneous infusion of donepezil (2 mg/kg/day) or vehicle, delivered by osmotic minipumps implanted 2 weeks before the cortical devascularization. In lesioned rats, donepezil treatment increased the number and the size of vesicular acetylcholine transporter immunoreactive boutons in comparison to vehicle treatment. Donepezil had no observable effect on any of these parameters in sham-operated animals. These results show that donepezil mitigates cholinergic neuronal degeneration in vivo. This suggests a neuroplastic activity of this drug and provides evidence for a potential use of donepezil as a disease modifier in neurodegenerative diseases such as AD.

Author information

Author/s: Ginestet, Laure (L); Ferrario, Juan E (JE); Raisman-Vozari, Rita (R); Hirsch, Etienne C (EC); Debeir, Thomas (T);

Affiliation: INSERM, UMR-679, Neurology and Experimental Therapeutics, Hôpital de la Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2007-Jul; vol 102 (issue 2) : pp 434-40

Dates: Created 2007/06/28; Completed 2007/09/07; Revised 2007/11/15;

PMID: 17394553, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholine - metabolism Alzheimer Disease - drug therapy; metabolism; physiopathology Animals Basal Nucleus of Meynert - drug effects; metabolism; physiopathology Cerebral Cortex - drug effects; metabolism; physiopathology Cholinergic Fibers - drug effects; metabolism Cholinesterase Inhibitors - pharmacology; therapeutic use Disease Models, Animal Growth Cones - drug effects; metabolism Indans - pharmacology; therapeutic use Male

Male Nerve Degeneration - drug therapy; metabolism; physiopathology Nerve Regeneration - drug effects; physiology Neural Pathways - drug effects; metabolism; physiopathology Neuronal Plasticity - drug effects; physiology Piperidines - pharmacology; therapeutic use Presynaptic Terminals - drug effects; metabolism; pathology Rats Rats, Sprague-Dawley Stroke - drug therapy; metabolism; physiopathology Vesicular Acetylcholine Transport Proteins - metabolism

Associated Chemicals: Cholinesterase Inhibitors (0) ; Indans (0) ; Piperidines (0) ; Slc18a3 protein, rat (0) ; Vesicular Acetylcholine Transport Proteins (0) ; donepezil (120011-70-3) ; Acetylcholine (51-84-3)

Related articles

These are the highest related articles currently in the database:

• Acute cholinergic rescue of synaptic plasticity in the neurodegenerating cortex of anti-nerve-growth-factor mice. 27 Feb 2002
• Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis. 30 Dec 2001
• Chronic brain cytochrome oxidase inhibition selectively alters hippocampal cholinergic innervation and impairs memory: prevention by ladostigil. 25 Apr 2007
• Glutamate receptors in nucleus accumbens mediate regionally selective increases in cortical acetylcholine release. 27 Feb 2007
• Toward a neuro-cognitive animal model of the cognitive symptoms of schizophrenia: disruption of cortical cholinergic neurotransmission following repeated amphetamine exposure in attentional task-performing, but not non-performing, rats. 12 Feb 2007
• Eye drop NGF administration promotes the recovery of chemically injured cholinergic neurons of adult mouse forebrain. 21 Oct 2007
• Sundowning and circadian rhythm disorders in dementia. 29 Nov 2006
• [Pharmacological properties of donepezil hydrochloride (Aricept), a drug for Alzheimer's disease] 30 Dec 1999
• Tumor necrosis factor-alpha triggers cell death of sensitized potassium chloride-stimulated cholinergic neurons. 10 May 2003
• Nerve growth factor response to excitotoxic lesion of the cholinergic basal forebrain is slightly impaired in aged rats. 30 May 2003

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.