Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus

Autor: Lothar Lindemann, Eero Castrén, Tomi Rantamäki, Kert Mätlik, Moses V. Chao, Henri Autio, Urmas Arumäe, Marius C. Hoener
Rok vydání: 2011
Předmět:
Male
medicine.medical_specialty
Time Factors
medicine.drug_class
Enzyme-Linked Immunosorbent Assay
Tropomyosin receptor kinase B
Biology
Tropomyosin receptor kinase A
Hippocampus
Article
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Internal medicine
medicine
Animals
Immunoprecipitation
Receptor
trkB
Donepezil
Phosphorylation
Receptor
trkA
Cholinergic neuron
030304 developmental biology
Pharmacology
Analysis of Variance
0303 health sciences
Galantamine
Acetylcholinesterase
3. Good health
Mice
Inbred C57BL
Endocrinology
Gene Expression Regulation
nervous system
chemistry
Acetylcholinesterase inhibitor
Trk receptor
Indans
biology.protein
Tyrosine
Cholinergic
Cholinesterase Inhibitors
030217 neurology & neurosurgery
Signal Transduction
Neurotrophin
Zdroj: Neuropharmacology. 61:1291-1296
ISSN: 0028-3908
Popis: Acetylcholinesterase inhibitors are first-line therapies for Alzheimer’s disease. These drugs increase cholinergic tone in the target areas of the cholinergic neurons of the basal forebrain. Basal forebrain cholinergic neurons are dependent upon trophic support by nerve growth factor (NGF) through its neurotrophin receptor, TrkA. In the present study, we investigated whether the acetylcholinesterase inhibitors donepezil and galantamine could influence neurotrophin receptor signaling in the brain. Acute administration of donepezil (3 mg/kg, i.p.) led to the rapid autophosphorylation of TrkA and TrkB neurotrophin receptors in the adult mouse hippocampus. Similarly, galantamine dose-dependently (3, 9 mg/kg, i.p.) increased TrkA and TrkB phosphorylation in the mouse hippocampus. Both treatments also increased the phosphorylation of transcription factor CREB and tended to increase the phosphorylation of AKT kinase but did not alter the activity of MAPK42/44. Chronic treatment with galantamine (3 mg/kg, i.p., 14 days), did not induce changes in hippocampal NGF and BDNF synthesis or protein levels. Our findings show that acetylcholinesterase inhibitors are capable of rapidly activating hippocampal neurotrophin signaling and thus suggest that therapies targeting Trk signaling may already be in clinical use in the treatment of AD.
Databáze: OpenAIRE
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