| Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioral outcome following neonatal hypoxia-ischemia in rats. | |
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MedLine Citation:
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PMID: 22041713 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low-birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the 'female protection' following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI. |
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Authors:
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C A Hill; M L Alexander; L D McCullough; R H Fitch |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-10-27 |
Journal Detail:
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Title: Developmental neuroscience Volume: 33 ISSN: 1421-9859 ISO Abbreviation: Dev. Neurosci. Publication Date: 2011 |
Date Detail:
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Created Date: 2012-03-21 Completed Date: 2012-07-18 Revised Date: 2012-07-23 |
Medline Journal Info:
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Nlm Unique ID: 7809375 Medline TA: Dev Neurosci Country: Switzerland |
Other Details:
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Languages: eng Pagination: 494-504 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
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University of Connecticut, Storrs, Conn., USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Behavior, Animal / physiology* Benzoquinones / pharmacology Female Hypoxia-Ischemia, Brain / metabolism* Male Rats Rats, Wistar Sex Characteristics* X-Linked Inhibitor of Apoptosis Protein / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HD049792/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzoquinones; 0/X-Linked Inhibitor of Apoptosis Protein; 550-24-3/embelin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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