ABSTRACT
Maternal alcohol consumption during pregnancy may cause neurocognitive and behavioral disorders that can persist until adulthood. Epidemiological data has revealed an alarming increase in the frequency of alcohol intake in pregnant women. Nutritional variables may also have an impact on the behavioral alterations occasioned by alcohol during development. Moreover, omega-3, a polyunsaturated fatty acid necessary for normal brain development, is deficient in ethanol-treated animals. Although studies have shown that omega-3 supplementation after prenatal ethanol (EtOH) treatment improves some disorders, there are no reports about acute treatment with omega-3 in binge alcohol neurotoxic models during postnatal development. The goal of this study was to determine whether an administration of omega-3, after an acute ethanol dose in neonates, would be able to attenuate alcohol effects in offspring. Male/ female rats were administered ethanol (2.5â¯g/kg s.c. at 0 and 2â¯h) or saline on postnatal day (PND) 7, with a single dose of omega-3 (720â¯mg/kg) 15â¯min after the last alcohol injection. It was have found that EtOH-treated animals showed hyperlocomotion on PND 14 (pre-juvenile), and anxiety-like behavior was observed at all the three ages studied. Administration of omega-3 after EtOH treatment reduced hyperlocomotion and the anxiety-like behaviors on PND 14, but did not diminish the anxiety on either PND 20 or 30 (juvenile). In conclusion, acute ethanol exposure produced neurobehavioral alterations that persisted in the offspring, with omega-3 able to ameliorate these effects on PND 14. These data are relevant considering that omega-3 administration may have therapeutic effects through mitigating some of ethanol´s damaging consequences.
Subject(s)
Fatty Acids, Omega-3/pharmacology , Fetal Alcohol Spectrum Disorders/metabolism , Fetal Alcohol Spectrum Disorders/prevention & control , Alcohol Drinking/adverse effects , Alcohol Drinking/physiopathology , Animals , Animals, Newborn/physiology , Anxiety/etiology , Anxiety/metabolism , Binge Drinking/metabolism , Binge Drinking/physiopathology , Ethanol/adverse effects , Fatty Acids, Omega-3/metabolism , Female , Fetal Alcohol Spectrum Disorders/psychology , Locomotion/drug effects , Male , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , RatsABSTRACT
Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 µg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.