1. Depletion of polysialic acid from neural cell adhesion molecule (PSA-NCAM) increases CA3 dendritic arborization and increases vulnerability to excitotoxicity.
- Author
-
McCall T, Weil ZM, Nacher J, Bloss EB, El Maarouf A, Rutishauser U, and McEwen BS
- Subjects
- Analysis of Variance, Animals, Body Mass Index, CA3 Region, Hippocampal drug effects, CA3 Region, Hippocampal metabolism, Dendrites drug effects, Dendrites ultrastructure, Disease Models, Animal, Excitatory Amino Acid Agonists toxicity, Fluoresceins, Gene Expression Regulation drug effects, Kainic Acid toxicity, Male, Metalloendopeptidases pharmacology, Nerve Degeneration chemically induced, Nerve Degeneration pathology, Neural Cell Adhesion Molecules drug effects, Organic Chemicals, Pyramidal Cells drug effects, Pyramidal Cells metabolism, Pyramidal Cells ultrastructure, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate genetics, Receptors, N-Methyl-D-Aspartate metabolism, Silver Staining, Stress, Psychological metabolism, Stress, Psychological physiopathology, CA3 Region, Hippocampal pathology, Dendrites pathology, Neural Cell Adhesion Molecules metabolism, Pyramidal Cells pathology, Sialic Acids deficiency, Stress, Psychological pathology
- Abstract
Chronic immobilization stress (CIS) shortens apical dendritic trees of CA3 pyramidal neurons in the hippocampus of the male rat, and dendritic length may be a determinant of vulnerability to stress. Expression of the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in the hippocampal formation is increased by stress, while PSA removal by Endo-neuraminidase-N (endo-N) is known to cause the mossy fibers to defasciculate and synapse ectopically in their CA3 target area. We show here that enzymatic removal of PSA produced a remarkable expansion of dendritic arbors of CA3 pyramidal neurons, with a lesser effect in CA1. This expansion eclipsed the CIS-induced shortening of CA3 dendrites, with the expanded dendrites of both no-stress-endo-N and CIS-endo-N rats being longer than those in no-stress-control rats and much longer than those in CIS-control rats. As predicted by the hypothesis that endo-N-induced dendritic expansion might increase vulnerability to excitotoxic challenge, systemic injection with kainic acid, showed markedly increased neuronal degeneration, as assessed by fluorojade B histochemistry, in rats that had been treated with endo-N compared to vehicle-treated rats throughout the entire hippocampal formation. PSA removal also exacerbated the CIS-induced reduction in body weight and abolished effects of CIS on NPY and NR2B mRNA levels. These findings support the hypothesis that CA3 arbor plasticity plays a protective role during prolonged stress and clarify the role of PSA-NCAM in stress-induced dendritic plasticity., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF