TY - JOUR
T1 - N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion
AU - Impellizzeri, Daniela
AU - Siracusa, Rosalba
AU - Cordaro, Marika
AU - Crupi, Rosalia
AU - Peritore, Alessio Filippo
AU - Gugliandolo, Enrico
AU - D'Amico, Ramona
AU - Petrosino, Stefania
AU - Evangelista, Maurizio
AU - Di Paola, Rosanna
AU - Cuzzocrea, Salvatore
PY - 2019
Y1 - 2019
N2 - Aim: Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, animals were orally administered with 10 mg/kg of PEA-OXA daily for 15 days. Results: Brain tissues were handled for histological, immunohistochemical, western blot, and immunofluorescence analysis. PEA-OXA treatment evidently reduced the histological alterations and neuronal death induced by VaD and additionally improved behavioral deficits. Further, PEA-OXA decreased GFAP and Iba-1, markers of astrocytes, and microglia activation, as well as increased MAP-2, a marker of neuron development. Moreover, PEA-OXA reduced oxidative stress, modulated Nrf2-mediated antioxidant response, and inhibited the apoptotic process. Innovation: Some drugs may demonstrate their healing potential by regulating neuroinflammation, rather than by their habitually attributed actions only. Palmitoylethanolamide (PEA) is a prototype ALIAmide, well-known for its analgesic, anti-inflammatory, and neuroprotective properties. The inhibition of PEA degradation by targeting NAAA, its catabolic enzyme, is a different approach for treating neuroinflammation. This research offers new insight into the mechanism of PEA-OXA-induced neuroprotection. Conclusion: Thus, the modulation of intracellular NAAA by PEA-OXA could offer a novel means of controlling neuroinflammatory conditions associated with VaD.
AB - Aim: Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, animals were orally administered with 10 mg/kg of PEA-OXA daily for 15 days. Results: Brain tissues were handled for histological, immunohistochemical, western blot, and immunofluorescence analysis. PEA-OXA treatment evidently reduced the histological alterations and neuronal death induced by VaD and additionally improved behavioral deficits. Further, PEA-OXA decreased GFAP and Iba-1, markers of astrocytes, and microglia activation, as well as increased MAP-2, a marker of neuron development. Moreover, PEA-OXA reduced oxidative stress, modulated Nrf2-mediated antioxidant response, and inhibited the apoptotic process. Innovation: Some drugs may demonstrate their healing potential by regulating neuroinflammation, rather than by their habitually attributed actions only. Palmitoylethanolamide (PEA) is a prototype ALIAmide, well-known for its analgesic, anti-inflammatory, and neuroprotective properties. The inhibition of PEA degradation by targeting NAAA, its catabolic enzyme, is a different approach for treating neuroinflammation. This research offers new insight into the mechanism of PEA-OXA-induced neuroprotection. Conclusion: Thus, the modulation of intracellular NAAA by PEA-OXA could offer a novel means of controlling neuroinflammatory conditions associated with VaD.
KW - Amidohydrolases
KW - Animals
KW - Anti-Inflammatory Agents
KW - Apoptosis
KW - Carotid Stenosis
KW - Dementia, Vascular
KW - Disease Models, Animal
KW - Inflammation
KW - Male
KW - Mice
KW - Neuroprotection
KW - Neuroprotective Agents
KW - Oxazoles
KW - Oxazoline
KW - Oxidative Stress
KW - Oxidative stress
KW - Palmitoylethanolamide
KW - Amidohydrolases
KW - Animals
KW - Anti-Inflammatory Agents
KW - Apoptosis
KW - Carotid Stenosis
KW - Dementia, Vascular
KW - Disease Models, Animal
KW - Inflammation
KW - Male
KW - Mice
KW - Neuroprotection
KW - Neuroprotective Agents
KW - Oxazoles
KW - Oxazoline
KW - Oxidative Stress
KW - Oxidative stress
KW - Palmitoylethanolamide
UR - http://hdl.handle.net/10807/151605
UR - https://0-www-sciencedirect-com.opac.unicatt.it/science/article/pii/s0969996118305382
U2 - 10.1016/j.nbd.2019.01.007
DO - 10.1016/j.nbd.2019.01.007
M3 - Article
SN - 0969-9961
VL - 125
SP - 77
EP - 91
JO - Neurobiology of Disease
JF - Neurobiology of Disease
ER -