Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer’s disease by exerting anti-inflammatory and neuroprotective effects
| Autor: | Caterina Scuderi, Maria Rosanna Bronzuoli, Roberta Facchinetti, Lorenzo Pace, Luca Ferraro, Kevin Donald Broad, Gaetano Serviddio, Francesco Bellanti, Gianmauro Palombelli, Giulia Carpinelli, Rossella Canese, Silvana Gaetani, Luca Steardo, Tommaso Cassano |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Magnetic Resonance Spectroscopy Microdialysis Anti-Inflammatory Agents Hippocampus Palmitic Acidstau Proteins 129 Strain Inbred C57BL Transgenic chemistry.chemical_compound Mice 0302 clinical medicine Hippocampal 3×Tg-AD mice Behavior Animal Neurodegeneration Age Factors food and beverages Alzheimer's disease palmitoylethanolamide astrocyte MRI/MRS Magnetic Resonance Imaging Psychiatry and Mental health Neuroprotective Agents Ethanolamines Mice 129 Strain Context (language use) Mice Transgenic tau Proteins Palmitic Acids Neuroprotection Article NO lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Neurochemical Alzheimer Disease medicine Animals Learning Cognitive Dysfunction CA1 Region Hippocampal lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neuroinflammation Inflammation Behavior Palmitoylethanolamide Memory Disorders Amyloid beta-Peptides Animal business.industry medicine.disease Symptomatic relief Amides Mice Inbred C57BL Disease Models Animal 030104 developmental biology chemistry Disease Models Age Factors Alzheimer Disease Amyloid beta-Peptides Animals Anti-Inflammatory Agents Behavior AnimalCA1 Region Hippocampal Cognitive Dysfunction Disease Models Animal Ethanolamines Inflammation Learning Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Male Memory Disorders Mice Mice 129 Strain Mice Inbred C57BL Mice Transgenic Microdialysis Neuroprotective Agents Palmitic Acidstau Proteins AnimalCA1 Region business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 8, Iss 1, Pp 1-19 (2018) Translational Psychiatry |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/s41398-017-0076-4 |
| Popis: | In an aging society, Alzheimer’s disease (AD) exerts an increasingly serious health and economic burden. Current treatments provide inadequate symptomatic relief as several distinct pathological processes are thought to underlie the decline of cognitive and neural function seen in AD. This suggests that the efficacy of treatment requires a multitargeted approach. In this context, palmitoylethanolamide (PEA) provides a novel potential adjunct therapy that can be incorporated into a multitargeted treatment strategy. We used young (6-month-old) and adult (12-month-old) 3×Tg-AD mice that received ultramicronized PEA (um-PEA) for 3 months via a subcutaneous delivery system. Mice were tested with a range of cognitive and noncognitive tasks, scanned with magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS), and neurochemical release was assessed by microdialysis. Potential neuropathological mechanisms were assessed postmortem by western blot, reverse transcription–polymerase chain reaction (RT-PCR), and immunofluorescence. Our data demonstrate that um-PEA improves learning and memory, and ameliorates both the depressive and anhedonia-like phenotype of 3×Tg-AD mice. Moreover, it reduces Aβ formation, the phosphorylation of tau proteins, and promotes neuronal survival in the CA1 subregion of the hippocampus. Finally, um-PEA normalizes astrocytic function, rebalances glutamatergic transmission, and restrains neuroinflammation. The efficacy of um-PEA is particularly potent in younger mice, suggesting its potential as an early treatment. These data demonstrate that um-PEA is a novel and effective promising treatment for AD with the potential to be integrated into a multitargeted treatment strategy in combination with other drugs. Um-PEA is already registered for human use. This, in combination with our data, suggests the potential to rapidly proceed to clinical use. |
| Databáze: | OpenAIRE |
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