Abstract
Understanding the mechanisms underlying the selective susceptibility to ischemia of the CA3 region is very important to explain the neuropathology of memory loss after brain ischemia. We used a rat model to study changes in gene expression of the amyloid protein precursor and its cleaving enzymes and tau protein in the hippocampal CA3 sector, after transient 10-min global brain ischemia with survival times of 2, 7, and 30 days. The expression of the α-secretase gene was below control values at all times studied. But, the expression of the β-secretase gene was below the control values at 2–7 days after ischemia and the maximal increase in its expression was observed on day 30. Expression of the presenilin 1 gene was significantly elevated above the control values at 2–7 days after ischemia and decreased below the control values at day 30. Expression of the presenilin 2 gene showed an opposite trend to the expression of presenilin 1. Expression of the amyloid protein precursor gene after ischemia was at all times above the control values with a huge significant overexpression on day 7. Additionally, the expression of the tau protein gene was below the control values 2 days after ischemia, but the significant increase in its expression was observed on days 7–30. Data show that brain ischemia activates neuronal changes and death in the CA3 region of the hippocampus in a manner dependent on amyloid and tau protein, thus determining a new and important way to regulate the survival and/or death of ischemic neurons.
Highlights
The hippocampus is an important part of the brain due to its anatomical structure and physiological functions, especially in the area related to learning and memory under normal conditions and dementia in Alzheimer’s disease and brain injury after ischemia [1,2,3,4,5,6,7]
The expression of the tau protein gene was below the control values 2 days after ischemia, but the significant increase in its expression was observed on days 7–30
In the CA3 region of the hippocampus, the expression of the α-secretase (ADAM10) gene after 10-min brain ischemia with a survival of 2, 7, and 30 days was below the control values
Summary
The hippocampus is an important part of the brain due to its anatomical structure and physiological functions, especially in the area related to learning and memory under normal conditions and dementia in Alzheimer’s disease and brain injury after ischemia [1,2,3,4,5,6,7]. Morphological observations have shown an increased number of disrupted pyramidal neurons in the CA3 region with acute and chronic lesions [11, 12] during 2 years of survival following brain ischemia [9] as one of the characteristic features for the development of dementia in Alzheimer’s disease [10] It seems that changes in pyramidal neurons, in particular in the hippocampus, such as the CA3 region, may play a significant role in memory deficits that herald the onset of Alzheimer’s disease [5] and the development of Alzheimer’s disease dementia after brain injury due to ischemia-reperfusion [2, 4]
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