Acute sublethal global hypoxia induces transient increase of GAP-43 immunoreactivity in the striatum of neonatal rats

Synapse. 2007 Mar;61(3):124-37. doi: 10.1002/syn.20353.


We assessed immunoreactivity (IR) in the cerebral cortex (CC), hippocampus (Hipp), and striatum (ST) of a growth-associated protein, GAP-43, and of proteins of the synaptic vesicle fusion complex: VAMP-2, Syntaxin-1, and SNAP-25 (SNARE proteins) throughout postnatal development of rats after submitting the animals to acute global postnatal hypoxia (6.5% O(2), 70 min) at postnatal day 4 (PND4). In the CC only the IR of the SNARE protein SNAP-25 increased significantly with age. The hypoxic animals showed the same pattern of IR for SNAP-25, although with lower levels at PND11, and also a significant increase of VAMP-2. SNAP-25 (control): PND11 P < 0.001 vs. PND18, 25, and 40, SNAP-25 (hypoxic): P < 0.001 vs. PND18, 25, and 40; VAMP-2 (hypoxic): P < 0.05 PND11 vs. PND18, and P < 0.01 vs. PND25 and PND40; one-way ANOVA and Bonferroni post-test. In the Hipp, SNAP-25 and syntaxin-1 increased significantly with age, reaching a plateau at PND25 through PND40 in control animals (one-way ANOVA: syntaxin-1: P = 0.043; Bonferroni: NS; SNAP-25: P = 0.013; Bonferroni: P < 0.01 PND11 vs. PND40). Hypoxic rats showed higher levels of significance in the one-way ANOVA than controls (syntaxin-1: P = 0.009; Bonferroni: P < 0.05 PND11 vs. PND25 and P < 0.001 PND11 vs. PND40). In the ST, GAP-43 differed significantly among hypoxic and control animals and the two-way ANOVA revealed significant differences with age (F = 3.23; P = 0.037) and treatment (F = 4.84; P = 0.036). VAMP-2 expression also reached statistical significance when comparing control and treated animals (F = 6.25, P = 0.018) without changes regarding to age. Elevated plus maze test performed at PND40 indicated a lower level of anxiety in the hypoxic animals. At adulthood (12 weeks) learning, memory and locomotor abilities were identical in both groups of animals. With these results, we demonstrate that proteins of the presynaptic structures of the ST are sensitive to acute disruption of homeostatic conditions, such as a temporary decrease of the O(2) concentration. Modifications in the activity of these proteins could contribute to the long term altered responses to stress due to acute hypoxic insult in the neonatal period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aging / physiology
  • Animals
  • Animals, Newborn
  • Anxiety Disorders / etiology
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Atmosphere Exposure Chambers
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Corpus Striatum / metabolism*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • GAP-43 Protein / metabolism*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Hypoxia, Brain / metabolism*
  • Hypoxia, Brain / physiopathology
  • Immunohistochemistry
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology
  • Synaptosomal-Associated Protein 25 / metabolism
  • Syntaxin 1 / metabolism
  • Up-Regulation / physiology*
  • Vesicle-Associated Membrane Protein 2 / metabolism


  • GAP-43 Protein
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Vesicle-Associated Membrane Protein 2