A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats

• Published in: Experimental gerontology 2017-11, Vol.98, p.62-69
• Main Authors: Tesic, Vesna, Perovic, Milka, Zaletel, Ivan, Jovanovic, Mirna, Puskas, Nela, Ruzdijic, Sabera, Kanazir, Selma
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Aging - metabolism; Animals; Calpain - metabolism; Dexamethasone - administration & dosage; GAP-43 cleavage; GAP-43 phosphorylation; GAP-43 Protein - metabolism; GLCM texture analysis; Glucocorticoids - administration & dosage; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Male; Phosphorylation; Proteolysis; Rats, Wistar; Synaptophysin - metabolism; Up-Regulation; αII-spectrin cleavage
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2017.08.010

The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats. •Dexamethasone alters hippocampal expression of pre-synaptic proteins in aged rats.•Dexamethasone affects GAP-43 phosphorylation and proteolysis during aging.•GLCM reveals DEX-induced increase of GAP-43 and synaptophysin in aged rats.