Alterations of Mitophagy (BNIP3), Apoptosis (CASP3), and Autophagy (BECN1) Genes in the Frontal Cortex in an Ischemic Model of Alzheimer's Disease with Long-Term Survival.

Abstract

Introduction: Currently, there is no information on changes in the mitophagy (BNIP3), apoptosis (CASP3), and autophagy (BECN1) genes in the frontal cortex after brain ischemia with animal survival for 2 years. Furthermore, it is not known whether the BNIP3, CASP3, and BECN1 genes possess any influence on neurons in the frontal cortex due to ischemia.

Aim: The goal of the investigation was to evaluate alterations in the behavior of BNIP3, CASP3, and BECN1 genes in the frontal cortex following ischemia with survival of 2 years.

Materials and methods: Gene expression was assessed using an RT-PCR protocol at 2-30 days and 6-24-months after ischemia.

Results: BECN1 gene expression after ischemic injury was lower than the controlgroup during 7-30- days and 18 months, whereas overexpression was noted after 2 days, 6-, 12- and 24 months. In the case of BNIP3 gene expression, it was lower than the control group for 2-7 days and higher than the control throughout the remaining time after ischemia. Increased expression of the CASP3 gene was observed except on days 7-30 following ischemia when its expression was lower compared to control values.

Discussion: The data seem to indicate that the observed changes in gene expression may reflect the activation and inhibition of different mechanisms involved in the advancement of neurodegeneration after ischemia.

Conclusion: Overexpression of BECN1gene is likely to be associated with the induction of neuroprotective phenomena, whereas overexpression of BNIP3 and CASP3 genes can cause harmful effects.