P2‐463: LXR agonist treatment of a transgenic mouse model of Alzheimer's disease: Effects on behavioral, electrophysiological and immunohistochemical markers
| Autor: | Inga Kadish, Olivier Thibault, Philip W. Landfield, James L. Searcy, Eric M. Blalock, Nada M. Porter, Amy L.S. Dowling, Jeremiah T. Phelps, Kuey-Chu C. Chen |
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| Rok vydání: | 2008 |
| Předmět: |
Agonist
medicine.medical_specialty Epidemiology medicine.drug_class Neuroprotection Nicotine Cellular and Molecular Neuroscience chemistry.chemical_compound Developmental Neuroscience Internal medicine medicine Quisqualic acid business.industry Health Policy Neurodegeneration medicine.disease Psychiatry and Mental health Nicotinic agonist Endocrinology Gliosis chemistry Neurology (clinical) Geriatrics and Gerontology medicine.symptom Alzheimer's disease business medicine.drug |
| Zdroj: | Alzheimer's & Dementia. 4 |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1016/j.jalz.2008.05.1542 |
| Popis: | identified SEN12333 (WAY-317538) as a full agonist with an EC50 of 1.2 microM and selective over related receptors. In previous experiments, this new alpha7 nAChR agonists has demonstrated pro-cognitive properties in both Alzheimer disease as well as schizophrenia oriented behavioural tests in rodents. Here we describe experiments aimed to evaluate the neuroprotective property of this compound in in vivo models of neurodegeneration in comparison with nicotine and to investigate the mechanisms of neuroprotection. Results: Five microL of 0.5 M quisqualic acid solution injected into the nucleus basalis magnocellularis (NBM) of rats resulted in a highly significant decrease in the number of ChAT-positive neurons, massive reactive gliosis, involving both astrocytes and microglia, and a significant increase in p38-MAPK expression. A sub-chronic treatment with 3 mg/kg SEN12333 or 0.3 mg/kg nicotine for 7 days significantly attenuated the decrease in the number of ChAT-positive neurons in this brain region demonstrating neuroprotective effects. Conclusions: These effects may be relevant for treating neurodegenerative diseases such as Alzheimer’s disease. The ability of nicotinic agonist-treatments to protect brain tissues from gliosis and inflammation will be discussed. |
| Databáze: | OpenAIRE |
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