NAP Enhances Neurodevelopment of Newborn Apolipoprotein E-Deficient Mice Subjected to Hypoxia
Autor: | Illana Gozes, Shaul Harel, Zipora Speiser, Naam Kariv, Michael Rotstein, Haim Bassan |
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Rok vydání: | 2006 |
Předmět: |
Apolipoprotein E
medicine.medical_specialty Morris water navigation task Brain damage Motor Activity Weight Gain Neuroprotection Mice Apolipoproteins E Internal medicine Reflex mental disorders medicine Animals Hypoxia Maze Learning Pharmacology business.industry Brain Hypoxia (medical) Mice Inbred C57BL Nap Memory Short-Term Neuroprotective Agents Endocrinology Animals Newborn Anesthesia Molecular Medicine medicine.symptom business Oligopeptides Weight gain |
Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 319:332-339 |
ISSN: | 1521-0103 0022-3565 |
DOI: | 10.1124/jpet.106.106898 |
Popis: | Perinatal hypoxic injury is associated with significant neonatal morbidity and long-term neurodevelopmental complications. NAP, a peptide derived from ADNP (activity-dependent neuroprotective protein), has previously shown neuroprotective abilities in various adult animal models. To evaluate its neuroprotective role in neonatal hypoxic-ischemic injury, we evaluated the neurodevelopmental outcome in apolipoprotein E (ApoE)-deficient (knockout) mice (a breed prone to brain damage during hypoxic insult) exposed to postnatal global hypoxic damage with and without treatment with NAP. ApoE-deficient (n = 80) and control (C57B6) mice pups (n = 81) were exposed to postnatal global hypoxia (35 min of 8% O(2) within 24 h of birth) or room air with or without subsequent subcutaneous NAP treatment during postnatal days 1 to 14. Pups were then evaluated for neonatal motor reflex attainment, spatial learning ability in the Morris water maze, and locomotor open-field activity. The C57B6 and ApoE-deficient anoxic groups showed significantly slower achievement of neonatal reflexes, diminished locomotor activity, and diminished spatial learning ability compared with their control groups. This was more pronounced in the anoxic ApoE-deficient pups. NAP treatment had a pronounced effect on neurodevelopmental outcome in both breeds, particularly in the ApoE-deficient mice. ApoE-deficient and control mouse pups exposed to postnatal hypoxia and treated with NAP showed improvement in neurodevelopmental outcome compared with nontreated mice pups. ApoE-deficient mice show a greater susceptibility to hypoxic damage and better response to NAP treatment. |
Databáze: | OpenAIRE |
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