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Palmitoylethanolamide Enhances Brain‐Derived Neurotrophic Factor Production and Neurogenesis in the Hippocampus Following Ischemic Brain Injury
Author(s) -
Cuzzocrea Salvatore,
Crupi Rosalia,
Paterniti Irene,
Impellizzeri Daniela,
Campolo Michela,
Esposito Emanuela
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1177.13
Subject(s) - dentate gyrus , palmitoylethanolamide , creb , neurotrophic factors , brain derived neurotrophic factor , neurogenesis , neuroscience , glial fibrillary acidic protein , subventricular zone , doublecortin , ischemia , medicine , hippocampus , subgranular zone , endocrinology , biology , microbiology and biotechnology , neural stem cell , transcription factor , receptor , biochemistry , immunohistochemistry , stem cell , cannabinoid receptor , gene , agonist
Stroke is the third leading cause of death and the leading cause of long‐term disability in adults. To counteract the ischemic brain injury, a new therapeutic approach has been employed by using palmitoylethanolamide (PEA). Ischaemic injury was induced for 2 h by middle cerebral artery occlusion (MCAo) followed by 24‐h reperfusion. PEA (10 mg/kg, i.p.) was administered by intraperitoneally injection twice, at 1 after the onset of ischemia and 6 h after reperfusion. In the present study using a transient ischemia model, we showed that (1) PEA induced the phosphorylation of extracellular signal‐regulated kinases 1/2 (ERK1/2) and cAMP response element‐binding protein (CREB) in the hippocampus after ischemia; (2) PEA increased the expression of brain‐derived neurotrophic factor (BDNF), a representative neurotrophic factor in the central nervous system, in the hippocampal dentate gyrus, and most BDNF‐positive cells were also stained with anti‐glial fibrillary acidic protein (one of the major intermediate filament proteins of mature astrocytes) and (3) PEA increased doublecortin positive neuronal precursor cells in the dentate gyrus subventricular zone or subgranular zone. These results suggest that PEA has the ability to induce BDNF production in astrocytes and enhance neurogenesis after brain ischemia, which may be mediated by activation of ERK1/2 and CREB.