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Updated: Apr 20, 2026

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by
A C Pascual1, A M Martín-Moreno2, N M Giusto1
1Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000 Bahía Blanca, Argentina.
Fatty acid amide hydrolase activity, crucial for endocannabinoid regulation, decreases in Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Anandamide, an endocannabinoid, plays a role in neuroprotection.
- Fatty acid amide hydrolase (FAAH) regulates anandamide levels by degrading it.
- Understanding FAAH activity in aging and Alzheimer's disease (AD) is crucial.
Purpose of the Study:
- To characterize anandamide breakdown via FAAH in physiological and pathological aging.
- To investigate the regulation of FAAH activity by CB1 and CB2 receptor agonists.
Main Methods:
- Analysis of FAAH activity in human cortical membranes (controls and AD patients).
- Measurement of FAAH activity in rat cerebral cortex (adults and aged).
- Assessment of agonist effects (JWH-133, WIN55,212-2) on anandamide hydrolysis.
Main Results:
- FAAH activity decreased in the frontal cortex of AD patients, mimicked by Aβ(1-40) peptide.
- FAAH activity showed differential changes in aged rat brain membranes and synaptosomes.
- CB1/CB2 agonists differentially modulated anandamide hydrolysis in human AD and aged rats.
Conclusions:
- Anandamide availability is reduced in Alzheimer's disease.
- Anandamide availability is increased in physiological aging.
- Differential modulation of FAAH by cannabinoid receptor agonists impacts anandamide levels in AD and aging.
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