Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Beggiato, Sarah; Tomasini, Maria Cristina; Cassano, Tommaso; Ferraro, Luca

doi:10.3390/jcm9020428

Cited by 28 publications

(39 citation statements)

References 63 publications

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“…The observed effects (e.g., reduced reactive astrogliosis and restored neuronal trophic support) were superior in younger mice as compared to older mice, suggesting that PEA-um may be a promising strategy to slow AD progression in the early stages of the disease [ 90 , 91 ]. More recently, in the same 3×Tg-AD model, chronic oral administration of PEA-um (100 mg/kg/day for 3 months) also rescued cognitive deficit and decreased the hippocampal level of extracellular glutamate [ 77 ]. Again, a significant effect on neuroinflammation was observed, as shown by the almost complete inhibition of interleukin (IL)-6 increase in the hippocampus, and the reduced the production of ROS [ 77 ].…”

Section: Pre-clinical and Clinical Effects Of Pea In Micronized Anmentioning

confidence: 99%

“…More recently, in the same 3×Tg-AD model, chronic oral administration of PEA-um (100 mg/kg/day for 3 months) also rescued cognitive deficit and decreased the hippocampal level of extracellular glutamate [ 77 ]. Again, a significant effect on neuroinflammation was observed, as shown by the almost complete inhibition of interleukin (IL)-6 increase in the hippocampus, and the reduced the production of ROS [ 77 ]. Evaluation of co-ultraPEA-Lut has also been reported in the early stage of AD.…”

Section: Pre-clinical and Clinical Effects Of Pea In Micronized Anmentioning

confidence: 99%

“…After oral administration, PEA-m and PEA-um have repeatedly shown higher bioavailability and superior effects compared to naïve PEA [ 75 , 76 ]. PEA-um also penetrates into the central nervous system, as shown by the significant increase of PEA levels in the hippocampus, brain, and spinal cord after oral administration of PEA-um [ 76 , 77 ]. Finally, PEA-m and PEA-um have shown favorable safety profiles with no evidence of toxicity [ 78 ].…”

Section: Introductionmentioning

confidence: 99%

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Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries—A Systematic Review

Petrosino

Moriello

2020

IJMS

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Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named “non-neuronal cells.” In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells—and therefore the control of neuroinflammation—depends on the local “on demand” synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide—either by decreasing its degradation or exogenous administration—is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

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Section: Pre-clinical and Clinical Effects Of Pea In Micronized Anmentioning

confidence: 99%

Section: Pre-clinical and Clinical Effects Of Pea In Micronized Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries—A Systematic Review

Petrosino

Moriello

2020

IJMS

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“…In this context PEA can modulate ERβ protein expression to improve its anti-inflammatory properties. Indeed, the compound has been demonstrated effective in reducing neuroinflammation and neurodegeneration in several in vitro and in vivo models [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

A New Palmitoylethanolamide Form Combined with Antioxidant Molecules to Improve Its Effectivess on Neuronal Aging

et al. 2020

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Palmitoylethanolamide is a nutraceutical compound naturally produced in many plants and animal source foods, but the natural form is poorly water-soluble. It has demonstrated an anti-inflammatory role as a neuroprotective mediator, acting on several molecular targets of the central nervous system involved on brain aging process. In healthy adults, palmitoylethanolamide is an endogenous PPAR-α (peroxisome proliferator-activated receptor α) agonist through which it performs anti-inflammatory activity and provides its effects by activating the cannabinoid receptor. The different formulations of palmitoylethanolamide (micronized palmitoylethanolamide, FM-LipoMatrix® palmitoylethanolamide and FM-LipoMatrix® palmitoylethanolamide plus lipoic acid and vitamin D3) were analyzed starting from intestinal barrier, to verify their bioavailability, to in primary astrocytes in which cell viability, reactive oxygen species (ROS) and nitric oxide (NO) production, NFKB activity, MAPK, p53 and PPARα activities were investigated. Additionally, cannabinoid and estrogen receptors were analyzed using the western blot technique. The combination of palmitoylethanolamide in FM-LipoMatrix®, lipoic acid and vitamin D3 shows better absorption predicting an improvement on plasma concentration; this formulation also shows a reduction in ROS and NO production and the data show the interaction of palmitoylethanolamide with cannabinoids and estrogen receptors inhibiting neuroinflammatory markers. All these data support the hypothesis of a new potential strategy to restore brain function and slow down brain aging in humans.

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“…It also restored cell viability of glioma and neuroblastoma impaired by lipopolisaccaride and interferon-gamma treatment, reducing protein expression of both iNOS and COX-2 [ 211 ]. Um-PEA demonstrated oral bioavailability and its chronic administration reduced neuroinflammatory markers and showed neuroprotective effects in 3xTg-AD mice [ 210 , 219 , 302 , 303 ]. When comparing hippocampi of 6-month-old with 12-month-old 3xTg-AD mice, the younger animals did not show astrocyte hypertrophy (measured as an increase in GFAP immunoreactivity) but exhibited an ongoing intense neuroinflammatory process with high levels of iNOS, TNF-α, chemokines, and interleukins, whereas older mice showed significant astrocyte atrophy without elevation in neuroinflammatory markers.…”

Section: Astrocytes As Targets For Ad Therapeuticsmentioning

confidence: 99%

Alternative Targets to Fight Alzheimer’s Disease: Focus on Astrocytes

et al. 2021

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The available treatments for patients affected by Alzheimer’s disease (AD) are not curative. Numerous clinical trials have failed during the past decades. Therefore, scientists need to explore new avenues to tackle this disease. In the present review, we briefly summarize the pathological mechanisms of AD known so far, based on which different therapeutic tools have been designed. Then, we focus on a specific approach that is targeting astrocytes. Indeed, these non-neuronal brain cells respond to any insult, injury, or disease of the brain, including AD. The study of astrocytes is complicated by the fact that they exert a plethora of homeostatic functions, and their disease-induced changes could be context-, time-, and disease specific. However, this complex but fervent area of research has produced a large amount of data targeting different astrocytic functions using pharmacological approaches. Here, we review the most recent literature findings that have been published in the last five years to stimulate new hypotheses and ideas to work on, highlighting the peculiar ability of palmitoylethanolamide to modulate astrocytes according to their morpho-functional state, which ultimately suggests a possible potential disease-modifying therapeutic approach for AD.

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Chronic Oral Palmitoylethanolamide Administration Rescues Cognitive Deficit and Reduces Neuroinflammation, Oxidative Stress, and Glutamate Levels in A Transgenic Murine Model of Alzheimer’s Disease

Cited by 28 publications

References 63 publications

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries—A Systematic Review

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries—A Systematic Review

A New Palmitoylethanolamide Form Combined with Antioxidant Molecules to Improve Its Effectivess on Neuronal Aging

Alternative Targets to Fight Alzheimer’s Disease: Focus on Astrocytes

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