Related Experiment Video
Updated: Jul 16, 2026
09:15
Stereological Estimation of Cholinergic Fiber Length in the Nucleus Basalis of Meynert of the Mouse Brain
Published on: February 5, 2020
Donepezil induces a cholinergic sprouting in basocortical degeneration
Laure Ginestet1, Juan E Ferrario, Rita Raisman-Vozari
1INSERM, UMR-679, Neurology and Experimental Therapeutics, Hôpital de la Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France.
Journal of Neurochemistry
|March 31, 2007
Summary
Donepezil, an Alzheimer's disease (AD) therapy, demonstrated neurorestorative effects by preserving cholinergic neurons in a rat model. This suggests donepezil may modify neurodegenerative disease progression.
Area of Science:
- Neuroscience
- Pharmacology
- Neurodegenerative Diseases
Background:
- Acetylcholinesterase inhibitors are approved Alzheimer's disease (AD) therapies enhancing acetylcholine.
- Current treatments primarily offer symptomatic relief, lacking direct evidence of neurorestorative action.
- Investigating neurorestorative potential of donepezil in a validated AD model.
Purpose of the Study:
- To evaluate the in vivo neurorestorative effects of donepezil.
- To assess donepezil's impact on cholinergic neuronal degeneration.
- To explore donepezil's potential as a disease-modifying agent for AD.
Main Methods:
- Utilized a rat model of partial unilateral cortical devascularization.
- Administered donepezil (2 mg/kg/day) or vehicle via subcutaneous osmotic minipumps for 6 weeks.
- Quantified vesicular acetylcholine transporter (VAChT) immunoreactive boutons in lesioned and sham-operated rats.
Main Results:
- Donepezil treatment significantly increased the number and size of VAChT-immunoreactive boutons in lesioned rats compared to vehicle.
- No significant effects of donepezil were observed in sham-operated animals.
- Demonstrated mitigation of cholinergic neuronal degeneration by donepezil in vivo.
Conclusions:
- Donepezil exhibits neurorestorative properties by preserving cholinergic terminals.
- The findings suggest potential neuroplastic activity of donepezil.
- Donepezil may serve as a disease modifier for neurodegenerative conditions like AD.
Related Concept Videos
01:30Indirect-Acting Cholinergic Agonists: Pharmacological Actions
Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:11Direct-Acting Cholinergic Agonists: Therapeutic Uses
Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome.
01:26Cholinergic Antagonists: Therapeutic Uses
Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
00:59Direct-Acting Cholinergic Agonists: Pharmacological Actions
Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
01:28Cholinergic Antagonists: Pharmacological Actions
Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...