ABSTRACT
Title
Palmitoylethanolamide exerts neuroprotective actions in a murine model of Parkinson's disease
Authors
E. Esposito1, E. Mazzon2, I. Paterniti1, S. Cuzzocrea1,2
1Dept. of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy; 2IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy
1Dept. of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy; 2IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy
Abstract
Parkinson’s disease (PD) is characterized by the progressive loss of nigrostriatal dopamine neurons leading to motor disturbances and cognitive impairment. Current pharmacotherapy relieves PD symptoms temporarily but fails to prevent or slows down the disease progression. In this study, we investigated the molecular mechanisms by which palmitoylethanolamide (PEA) protects mouse nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity and neuroinflammation.
MPTP administration in dose of 20mg/kg, i.p (four injections at an interval of 2hr) significantly induced the Parkinson-like symptoms in mice (Przedborski et al., 2001) as indicated by impairment in locomotor activity, inability to correct posture, decreased tyrosine hydroxylase (TH) expression in the nigra-striatum, and oxidative stress. MPTP administration significantly impaired mitochondrial complex-I activity and redox activity, upregulated the apoptotic proteins and NF-κB levels as compared to vehicle group. PEA (10mg/kg) was administered chronically (i.p.), once a day for 7 days starting 24 hr after the last injection of MPTP. Treatment with PEA for 7days significantly reversed behavioral, biochemical, mitochondrial complex alterations as well as attenuated the induction of proinflammatory mediators in MPTP-treated groups. At 7 days after MPTP treatment, loss of TH-positive neurons in the substantia nigra was restored and infiltration of activated microglia and astrocytes was markedly decreased in the nigra-striatum by PEA treatment. Furthermore, PEA treatment was shown to increase the levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived factor (GDNF) in MPTP-treated mice, possibly indicating, at least in part, the mechanism of neuroprotection.
The findings of the present study substantiate the neuroprotective role of PEA in ameliorating MPTP-induced neurodegeneration in mice and suggest the possible therapeutic potential of PEA in the management of PD.
Przedborski et al. (2001). J Neurochem. 76, 1265-74.
MPTP administration in dose of 20mg/kg, i.p (four injections at an interval of 2hr) significantly induced the Parkinson-like symptoms in mice (Przedborski et al., 2001) as indicated by impairment in locomotor activity, inability to correct posture, decreased tyrosine hydroxylase (TH) expression in the nigra-striatum, and oxidative stress. MPTP administration significantly impaired mitochondrial complex-I activity and redox activity, upregulated the apoptotic proteins and NF-κB levels as compared to vehicle group. PEA (10mg/kg) was administered chronically (i.p.), once a day for 7 days starting 24 hr after the last injection of MPTP. Treatment with PEA for 7days significantly reversed behavioral, biochemical, mitochondrial complex alterations as well as attenuated the induction of proinflammatory mediators in MPTP-treated groups. At 7 days after MPTP treatment, loss of TH-positive neurons in the substantia nigra was restored and infiltration of activated microglia and astrocytes was markedly decreased in the nigra-striatum by PEA treatment. Furthermore, PEA treatment was shown to increase the levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived factor (GDNF) in MPTP-treated mice, possibly indicating, at least in part, the mechanism of neuroprotection.
The findings of the present study substantiate the neuroprotective role of PEA in ameliorating MPTP-induced neurodegeneration in mice and suggest the possible therapeutic potential of PEA in the management of PD.
Przedborski et al. (2001). J Neurochem. 76, 1265-74.