Dysregulation of Autophagy, Mitophagy, and Apoptotic Genes in the Medial Temporal Lobe Cortex in an Ischemic Model of Alzheimer's Disease

Abstract

Ischemic brain damage is a pathological incident that is often linked with medial temporal lobe cortex injury and finally its atrophy. Post-ischemic brain injury associates with poor prognosis since neurons of selectively vulnerable ischemic brain areas are disappearing by apoptotic program of neuronal death. Autophagy has been considered, after brain ischemia, as a guardian against neurodegeneration. Consequently, we have examined changes in autophagy (BECN 1), mitophagy (BNIP 3), and apoptotic (caspase 3) genes in the medial temporal lobe cortex with the use of quantitative reverse-transcriptase PCR following transient 10-min global brain ischemia in rats with survival 2, 7, and 30 days. The intense significant overexpression of BECN 1 gene was noted on the 2nd day, while on days 7-30 the expression of this gene was still upregulated. BNIP 3 gene was downregulated on the 2nd day, but on days 7-30 post-ischemia, there was a significant reverse tendency. Caspase 3 gene, associated with apoptotic neuronal death, was induced in the same way as BNIP 3 gene after brain ischemia. Thus, the demonstrated changes indicate that the considerable dysregulation of expression of BECN 1, BNIP 3, and caspase 3 genes may be connected with a response of neuronal cells in medial temporal lobe cortex to transient complete brain ischemia.

Keywords: Alzheimer’s disease; BECN 1; BNIP 3; brain ischemia; caspase 3; genes; rat; selective vulnerability; temporal cortex.

Fig.1

The mean expression levels of BECN 1 gene in the medial temporal lobe cortex in rats 2, 7, and 30 days after 10-min of global brain ischemia. Marked SEM–standard error of the mean. Indicated statistically significant difference in levels of gene expression between 2 and 30 days after 10-min of global brain ischemia (Kruskal-Wallis test). ^*p≤0.05.

Fig.2

The mean expression levels of BNIP 3 gene in the medial temporal lobe cortex in rats 2, 7, and 30 days after 10-min of global brain ischemia. Marked SEM–standard error of the mean. Indicated statistically significant differences in levels of gene expression between 2 and 7 and between 2 and 30 days after 10-min of global brain ischemia (Kruskal-Wallis test). ^*p≤0.05, ^**p≤0.01.

Fig.3

The mean expression levels of caspase 3 gene in the medial temporal lobe cortex in rats 2, 7, and 30 days after 10-min of global brain ischemia. Marked SEM–standard error of the mean. Indicated statistically significant differences in levels of gene expression between 2 and 7 and between 2 and 30 days after 10-min of global brain ischemia (Kruskal-Wallis test). ^*p≤0.05, ^**p≤0.01.