Bax modulates neuronal survivability while p53 is indifferent after Cytochrome C oxidative stress in the adult olfactory bulb in vivo

Abstract

Background: The granule and periglomerular cells of the olfactory bulb migrate from the sub-ventricular zone (SVZ) as progenitor cell forming the neuronal stream of the rostral olfactory bulb. These cells are characterized by their ability to divide while expressing adult proteins; a phenomenon attributed to the prolonged cell cycle and the regulatory activities of proteins which modulates apoptosis and proliferation in the developing nervous system. Of interest are the proteins concerned with tumor suppression (p53) and cell cycle exit (Bax) and how they regulate survivability of these neurons in the adult system after an induced oxidative stress. Purpose: This study sets to investigate the interplay between p53 and Bax in the adult olfactory bulb (periglomerular and granule cell layer),and how these proteins determine proliferation and neuronal survival after Cytochrome C induced-oxidative stress. Also, we demonstrate the effect of the induced-stress threshold on such regulation in vivo . Methods : Adult Wistar rats were segregated into three groups. 10 and 20 mg/Kg BW of potassium cyanide (KCN) was administered to the treatment groups for 15 days while the control received normal saline for the same duration. The olfactory bulb was dissected and processed for general histology and immunohistochemistry of p53/Bax in the periglomerular and granule cell layers. Total (Histology) and immunopositive (p53 and Bax) cell count was done using Image J. Subsequently, we determined the analysis of variance with significance. Results : We observed an increase in cell count for the 10mg/KgBW treatment; this was characterized by a significant decrease in Bax expression and no change in p53 expression when this treatment group was compared to the control. However, no change was observed in the total cell count for 20mg/Kg BW treatment for the same duration of exposure.Interestingly, there was also no significant change in Bax and p53 for this treatment when compared with the control. Conclusion: Although p53 plays an important role in development of the olfactory bulb neurons, our findings suggests it has little contribution in neuronal cell viability and proliferation in the adult olfactory bulb. No significant change in p53 was observed irrespective of treatment dose and cell count while Bax expression was reduced at 10mg/KgBW treatment and was associated with an increased cell count. We conclude that regulation of survival of neurons in the adult olfactory bulb, following induced-oxidative stress was more dependent of the expression of Bax and the threshold of the induced stress rather than p53 expression.