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Effects of age, experience and inter-alpha inhibitor proteins on working memory and neuronal plasticity after neonatal hypoxia-ischemia.

Abstract
Neonatal cerebral hypoxia-ischemia (HI) commonly results in cognitive and sensory impairments. Early behavioral experience has been suggested to improve cognitive and sensory outcomes in children and animal models with perinatal neuropathology. In parallel, we previously showed that treatment with immunomodulator Inter-alpha Inhibitor Proteins (IAIPs) improves cellular and behavioral outcomes in neonatal HI injured rats. The purpose of the current study was to evaluate the influences of early experience and typical maturation in combination with IAIPs treatment on spatial working and reference memory after neonatal HI injury. A second aim was to determine the effects of these variables on hippocampal CA1 neuronal morphology. Subjects were divided into two groups that differed with respect to the time when exposed to eight arm radial water maze testing: Group one was tested as juveniles (early experience, Postnatal day (P) 36-61) and adults (P88-113), and Group two was tested in adulthood only (P88-113; without early experience). Three treatment conditions were included in each experience group (HI+Vehicle, HI+IAIPs, and Sham subjects). Incorrect arm entries (errors) were compared between treatment and experience groups across three error types (reference memory (RM), working memory incorrect (WMI), working memory correct (WMC)). Early experience led to improved working memory performance regardless of treatment. Combining IAIPs intervention with early experience provided a long-term behavioral advantage on the WMI component of the task in HI animals. Anatomically, early experience led to a decrease in the average number of basal dendrites per CA1 pyramidal neuron for IAIP treated subjects and a significant reduction in basal dendritic length in control subjects, highlighting the importance of pruning in typical early life learning. Our results support the hypothesis that early behavioral experience combined with IAIPs improve outcome on a relativity demanding cognitive task, beyond that of a single intervention strategy, and appears to facilitate neuronal plasticity following neonatal brain injury.
AuthorsCynthia M Gaudet, Yow-Pin Lim, Barbara S Stonestreet, Steven W Threlkeld
JournalBehavioural brain research (Behav Brain Res) Vol. 302 Pg. 88-99 (Apr 01 2016) ISSN: 1872-7549 [Electronic] Netherlands
PMID26778784 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2016 Elsevier B.V. All rights reserved.
Chemical References
  • Alpha-Globulins
  • inter-alpha-inhibitor
Topics
  • Aging
  • Alpha-Globulins (pharmacology)
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • CA1 Region, Hippocampal (pathology)
  • Dendrites (drug effects, pathology, ultrastructure)
  • Disease Models, Animal
  • Hypoxia-Ischemia, Brain (complications, pathology)
  • Male
  • Maze Learning (drug effects)
  • Memory Disorders (drug therapy, etiology, pathology)
  • Memory, Short-Term (drug effects, physiology)
  • Neuronal Plasticity (drug effects, physiology)
  • Neurons (drug effects, ultrastructure)
  • Rats
  • Rats, Wistar
  • Silver Staining

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