Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease
| Autor: | Alessandra Ottani, Eleonora Vandini, Anita Calevro, Davide Zaffe, Maria Galantucci, Alessandra Bitto, Paola Sena, Fabrizio Canalini, Daniela Giuliani, Maurizio Sandrini, Francesco Squadrito, Laura Neri, Salvatore Guarini |
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| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
Male medicine.medical_specialty Zif268 Spatial Learning Hippocampus Mice Transgenic Neocortex Brain damage Neuroprotection Peptides Cyclic Learning and memory NDP-alpha-MSH Alzheimer Disease Memory Internal medicine medicine Animals Cognitive decline Alzheimer׳s disease Melanocortins Tg2576 mice beta-amyloid Early Growth Response Protein 1 Pharmacology Amyloid beta-Peptides Disease Models Animal Endocrinology medicine.anatomical_structure Neuroprotective Agents nervous system Cerebral cortex alpha-MSH Receptor Melanocortin Type 4 medicine.symptom Melanocortin Psychology Cognition Disorders |
| Zdroj: | European journal of pharmacology. 740 |
| ISSN: | 1879-0712 |
| Popis: | We previously reported that melanocortins induce neuroprotection in experimental acute and chronic neurodegenerative conditions, including Alzheimer׳s disease (AD) of mild severity. Here we investigated whether melanocortins afford neuroprotection and counteract cognitive decline in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). Saline-treated (days 1-50) control Tg2576 mice showed an impairment in spatial learning and memory, associated (at day 50, end of the study) with hippocampus at low levels of the synaptic activity-dependent gene Zif268, relevant brain changes such as cerebral cortex/hippocampus increased level of β-amyloid (Aβ) deposit, and neuronal loss, in comparison with wild-type animals. Treatment of Tg2576 mice (once daily at days 1-50) with a nanomolar dose of the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus level of Aβ deposit, decreased neuronal loss, increased hippocampus Zif268 expression and improved cognitive functions, relative to saline-treated Tg2576 mice. Pharmacological blockade of melanocortin MC4 receptors with the MC4 receptor antagonist HS024 prevented all favorable effects of NDP-α-MSH. Our data indicate that MC4 receptor-stimulating melanocortins are able to counteract cognitive decline in experimental AD of medium severity through induction of neuroprotection and improvement of synaptic transmission. After further studies, these agents could gain a role as disease modifying therapeutics for AD. |
| Databáze: | OpenAIRE |
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