دورية أكاديمية
أعرض في EDS

Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer's disease by exerting anti-inflammatory and neuroprotective effects.

التفاصيل البيبلوغرافية
العنوان: Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer's disease by exerting anti-inflammatory and neuroprotective effects.
المؤلفون: Scuderi C; Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University of Rome, Rome, Italy., Bronzuoli MR; Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University of Rome, Rome, Italy., Facchinetti R; Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University of Rome, Rome, Italy., Pace L; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy., Ferraro L; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy., Broad KD; UCL Institute of Opthalmology, University College, University College London, London, UK., Serviddio G; C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Bellanti F; C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Palombelli G; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy., Carpinelli G; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy., Canese R; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy., Gaetani S; Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University of Rome, Rome, Italy., Steardo L Jr; Department of Psychiatry, University of Naples SUN, Naples, Italy., Steardo L; Department of Physiology and Pharmacology 'V. Erspamer', SAPIENZA University of Rome, Rome, Italy. luca.steardo@uniroma1.it., Cassano T; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
المصدر: Translational psychiatry [Transl Psychiatry] 2018 Jan 31; Vol. 8 (1), pp. 32. Date of Electronic Publication: 2018 Jan 31.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101562664 Publication Model: Electronic Cited Medium: Internet ISSN: 2158-3188 (Electronic) Linking ISSN: 21583188 NLM ISO Abbreviation: Transl Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group
مواضيع طبية MeSH: Alzheimer Disease/*drug therapy , Amyloid beta-Peptides/*deficiency , Anti-Inflammatory Agents/*pharmacology , CA1 Region, Hippocampal/*drug effects , Cognitive Dysfunction/*drug therapy , Ethanolamines/*pharmacology , Inflammation/*drug therapy , Learning/*drug effects , Memory Disorders/*drug therapy , Neuroprotective Agents/*pharmacology , Palmitic Acids/*pharmacology , tau Proteins/*drug effects, Age Factors ; Alzheimer Disease/immunology ; Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Amides ; Animals ; Anti-Inflammatory Agents/administration & dosage ; Behavior, Animal/drug effects ; CA1 Region, Hippocampal/immunology ; CA1 Region, Hippocampal/metabolism ; CA1 Region, Hippocampal/physiopathology ; Cognitive Dysfunction/immunology ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Disease Models, Animal ; Ethanolamines/administration & dosage ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/physiopathology ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Memory Disorders/immunology ; Memory Disorders/metabolism ; Memory Disorders/physiopathology ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Transgenic ; Microdialysis ; Neuroprotective Agents/administration & dosage ; Palmitic Acids/administration & dosage
مستخلص: 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.
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المشرفين على المادة: 0 (Amides)
0 (Amyloid beta-Peptides)
0 (Anti-Inflammatory Agents)
0 (Ethanolamines)
0 (Neuroprotective Agents)
0 (Palmitic Acids)
0 (tau Proteins)
6R8T1UDM3V (palmidrol)
تواريخ الأحداث: Date Created: 20180201 Date Completed: 20181212 Latest Revision: 20201209
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5802581
DOI: 10.1038/s41398-017-0076-4
PMID: 29382825
قاعدة البيانات: MEDLINE
الوصف
تدمد:2158-3188
DOI:10.1038/s41398-017-0076-4