The Effect of Repeated Restraint Stress on Neuroglobin-Oligodendrocytes Functions in the CA3 Hippocampal Area and Their Involvements in the Signaling Pathways of the Stress-Induced Anxiety

The present work shows the biochemical and structural fundamentals for the stress induced anxiety and stress adjustment response of the CA3 hippocampus area. Adult male Wistar rats were repeatedly exposed to a 3 h day restraint stress, for either 3 or 6 days. The concentration of corticosterone and testosterone in the CA3 hippocampus area was divergent, while oxidative stress was progressively increased during the stress exposure. The mitochondrial lysis in the CA3 neurons confirmed the oxidative stress events. Immunohistochemical findings showed that oligodendrocytes (OCs) proliferation and neuroglobin (Ngb) expression were stimulated, whereas MeCP2 expression was decreased as a balance reaction in stress exposure under corticosterone signaling. Remarkably, ultrastructural changes such as mitochondrial lysis, endoplasmic reticulum swelling, and perivascular lysis with platelets adherence to endothelium in the CA3 area were seen in the 6th day of restraining. The anxiety-like behavior was noticed 6 days later after stress exposure. These results suggest that the duration of the exposure, but not the intensity of the stress, is the key factor in the stress-buffering function by the CA3 hippocampus area via up-regulation of the Ngb-OCs bionome. The imbalance of the Ngb-OCs communication may be involved in the development of CA3-dependent anxious behavior.