Protein-Energy Malnutrition Alters Hippocampal Plasticity-Associated Protein Expression following Global Ischemia in the Gerbil

Erin      J. Prosser-Loose; Valerie      M.K. Verge; Francisco      S. Cayabyab; Phyllis      G. Paterson

Abstract

Previously it has been demonstrated that protein-energy malnutrition (PEM) impairs habituation in the open field test following global ischemia. The present study examined the hypothesis that PEM exerts some of its deleterious effects on functional outcome by altering the post-ischemic expression of the plasticity-associated genes brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP- 43). Male, Mongolian gerbils (11-12wk) were randomized to either control diet (12.5% protein) or PEM (2% protein) for 4wk, and then underwent 5min bilateral common carotid artery occlusion or sham surgery. Tympanic temperature was maintained at 36.5± 0.5°C during surgery. Brains collected at 1, 3 and 7d post-surgery were processed by in situ hybridization or immunofluorescence. BDNF and trkB mRNA expression was increased in hippocampal CA1 neurons after ischemia at all time points and was not significantly influenced by diet. However, increased trkB protein expression after ischemia was exacerbated by PEM at 7d in the CA1 region. Post-ischemic GAP-43 protein increased at 3 and 7d in the CA1 region, and PEM intensified this response and extended it to the CA3 and hilar regions. PEM exerted these effects without exacerbating CA1 neuron loss caused by global ischemia. The findings suggest that PEM increases the stress response and/or hyper-excitability in the hippocampus after global ischemia. Nutritional care appears to have robust effects on plasticity mechanisms important to recovery after brain ischemia.

Keywords: Brain-derived neurotrophic factor, growth-associated protein-43, nutrition, plasticity, stroke, tropomyosin-related kinase B, nutrition, plasticity, CA1, brain ischemia, Ca2+, PEM, nuclear factor-κB, CA3, mRNA, GAP-43, BCCAO, CON-S, CON-I, PEM-S, OCT, In situ Hybridization, BDNF, trkB, Global Ischemia, Immunofluorescence, CON, DAPI, ±SEM, IDV