Decreased TrkA Gene Expression in Cholinergic Neurons of the Striatum and Basal Forebrain of Patients with Alzheimer's Disease
| Autor: | Baptiste Faucheux, Florence Boissière, Yves Agid, Merle Ruberg, Etienne C. Hirsch |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Silver Staining medicine.medical_specialty Gene Expression Receptors Nerve Growth Factor Striatum Biology Nucleus basalis Choline O-Acetyltransferase Nerve growth factor binding Prosencephalon Developmental Neuroscience Alzheimer Disease Proto-Oncogene Proteins Internal medicine medicine Humans RNA Messenger Receptor trkA Cholinergic neuron In Situ Hybridization Aged Aged 80 and over Neurons Basal forebrain Putamen Ventral striatum Receptor Protein-Tyrosine Kinases Immunohistochemistry Neostriatum medicine.anatomical_structure Nerve growth factor Endocrinology Cholinergic Fibers nervous system Neurology Autoradiography Female |
| Zdroj: | Experimental Neurology. 145:245-252 |
| ISSN: | 0014-4886 |
| DOI: | 10.1006/exnr.1997.6443 |
| Popis: | In addition to cortical pathology, Alzheimer's disease is characterized by a loss of cholinergic neurons in the basal forebrain and the ventral striatum. Since cholinergic neurons which degenerate in Alzheimer's disease are sensitive to nerve growth factor, a link between nerve growth factor sensitivity and the vulnerability of cholinergic neurons has been suspected. The purpose of this study was to determine, in cholinergic neurons, the level of expression of TrkA, the high affinity receptor for nerve growth factor, in control subjects and Alzheimer patients. The study was performed by in situ hybridization using a 35S-labeled RNA probe complementary to human TrkA mRNA on immunohistochemically identified cholinergic neurons of the nucleus basalis of Meynert, the ventral striatum, and the putamen in postmortem brains of patients with clinically and neuropathologically confirmed Alzheimer's disease and control subjects. In patients with Alzheimer's disease, a decrease in TrkA mRNA expression was observed in the nucleus basalis of Meynert (-75%, P < 0.001) and the ventral striatum (-41%, P < 0.01), where the cholinergic neurons degenerate, and also in the anterior (-43%, P < 0.01) and posterior (-51%, P < 0.01) parts of the putamen, where they are spared but display precocious signs of cell alterations. These results, taken in conjunction with the reduced choline acetyltransferase activity and our previously published data showing a loss of high affinity nerve growth factor binding in both the dorsal and the ventral striatum of patients with Alzheimer's disease, indicate that receptor loss and the consequent decrease in trophic support may be associated with the degeneration of cholinergic neurons during Alzheimer's disease. |
| Databáze: | OpenAIRE |
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