The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ-secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ-secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death.
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.
Abstract. Brain ischemia may be causally related with Alzheimer's disease. Presumably, -secretase and amyloid- protein precursor gene expression changes may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both -secretase and amyloid- protein precursor genes in the medial temporal lobe cortex with the use of quantitative rtPCR analysis following 10-min global brain ischemia in rats with survival of 2, 7, and 30 days. The greatest significant overexpression of -secretase gene was noted on the 2nd day, while on days 7-30 the expression of this gene was only modestly downregulated. Amyloid- protein precursor gene was downregulated on the 2nd day, but on days 7-30 postischemia, there was a significant reverse tendency. Thus, the demonstrated alterations indicate that the considerable changes of expression of -secretase and amyloid- protein precursor genes may be connected with a response of neurons in medial temporal lobe cortex to transient global brain ischemia. Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology.
Thus, presented changes suggest that the significant dysregulation of presenilin 2 gene may be connected with a response of neuronal cells to transient global brain ischemia due to cardiac arrest. Finally, the ischemia-induced gene dysregulation may play a key role in the late onset of Alzheimer's-type dementia.
The stromal-vascular cell fraction (SVF) of adipose tissue can be an abundant source of both multipotent and pluripotent stem cells, known as adipose-derived stem cells or adipose tissue-derived stromal cells (ADSCs). The SVF also contains vascular cells, targeted progenitor cells, and preadipocytes. Stromal cells isolated from adipose tissue express common surface antigens, show the ability to adhere to plastic, and produce forms that resemble fibroblasts. They are characterized by a high proliferation potential and the ability to differentiate into cells of meso-, ecto- and endodermal origin. Although stem cells obtained from an adult organism have smaller capabilities for differentiation in comparison to embryonic and induced pluripotent stem cells (iPSs), the cost of obtaining them is significantly lower. The 40 years of research that mainly focused on the potential of bone marrow stem cells (BMSCs) revealed a number of negative factors: the painful sampling procedure, frequent complications, and small cell yield. The number of stem cells in adipose tissue is relatively large, and obtaining them is less invasive. Sampling through simple procedures such as liposuction performed under local anesthesia is less painful, ensuring patient comfort. The isolated cells are easily grown in culture, and they retain their properties over many passages. That is why adipose tissue has recently been treated as an attractive alternative source of stem cells. Essential aspects of ADSC biology and their use in regenerative medicine will be analyzed in this article.
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