Brain energy metabolic impairment is one of the main features of Alzheimer’s disease (AD) and is considered an underlying factor involved in cognitive impairment. Therefore, brain energy metabolism may represent a new therapeutic target for AD medica

Background Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma. Material and methods In order to identify differences in the capacity for lactate exchange, human T-47D breast cancer cells and human glioblastoma T98G cells were grown under 4 % or 20 % oxygen conditions and examined for MCT1, MCT2 and MCT4 expression on plasma membranes by quantitative post embedding immunogold electron microscopy. Whereas previous studies on MCT expression in tumours have recorded mRNA and protein levels in cell extracts, we examined concentrations of the proteins in the microvillous plasma membrane protrusions specialized for transmembrane transport. Results In normoxia, both tumour cell types highly expressed the low affinity transporter MCT4, which is thought to mainly mediate monocarboxylate efflux, while for high affinity transport the breast tumour cells preferentially expressed MCT1 and the brain tumour cells resembled brain neurons in expressing MCT2, rather than MCT1. The expressions of MCT1 and MCT4 were upregulated in hypoxic conditions in both breast and brain tumour cells. The expression of MCT2 also increased in hypoxic breast cancer cells, but decreased in hypoxic brain tumour cells. Quantitative immunoblots showed similar hypoxia induced changes in the protein levels. Conclusion The differential expression and regulation of MCTs in the surface membranes of hypoxic and normoxic tumour cells of different types provide a foundation for innovation in tumour therapy through the selective targeting of MCTs. Selective inhibition of various MCTs could be an efficient way to quench an important energy source in both original breast tumour and metastatic cancer tissue in the brain.

Background: Physical exercise has been shown to improve cognitive and motor functions, promoting neurogenesis and demonstrating therapeutic benefits in neurodegenerative disorders. Nonetheless, it is crucial to investigate the cellular and molecular mechanisms by which this occurs. The study aimed to investigate and evaluate the effect of swimming exercise on the changes of mitochondrial proteins in the brains of rats with hypoxic ischemic encephalopathy (HIE). Methods: the vertical pole and Morris water maze tests were used to assess the animals’ motor and cognitive functions, and western blot and immunofluorescence of brain tissue were used to assess the biomarkers of mitochondrial apoptosis and cristae stability in response to exercise training. Four groups of rats were used: (1) sham sedentary group (SHAM, NT), (2) sham exercise training group (SHAM, T) (3) hypoxic ischemic encephalopathy sedentary group (HIE, NT), and (4) hypoxic ischemic encephalopathy exercise training group (HIE, T). Results: animals with HIE showed motor and cognitive deficits, as well as increased apoptotic protein expression. Exercise, on the other hand, improved motor and cognitive functions while also suppressing the expression of apoptotic proteins. Conclusions: By stabilizing the mitochondrial cristae and suppressing the apoptotic cascade, physical exercise provided neuroprotection in hypoxic ischemia-induced brain injury.

Alzheimers disease (AD) is one common degenerative disorder. However, the effects of miR-590-5p on AD and the mechanism on modulation of AD development were unclear. In this study, the miR-590-5p level in AD patients at mild, moderate, and severe stage as well as APP/PS1 transgenic mice was detected by qRT-PCR. The relationship of miR-590-5p and pellino-1 (PELI1) was identified by double luciferase reporter gene assay. Afterwards, both BV-2 and HT22 cells were exposed to β-amyloid (Aβ) peptides to mimic AD cell model. Then, the roles of miR-590-5p upregulation or PELI1 silence in cell proliferation and apoptosis were explored by CCK-8 assay and TUNEL assay, and the expression of apoptosis-related proteins was detected by western blotting. Furthermore, the involvements of the downstream Traf3/MAPK P38 pathway with the roles of miR-590-5p in AD were measured by western blotting. Our results showed that knockdown of miR-590-5p was found in AD patients, mice model, and Aβ-induced cell model. Notably, PELI1 was proved as a target gene of miR-590-5p. miR-590-5p mimic or PELI1 silence significantly promoted cell proliferation and inhibited cell apoptosis, as well as suppressed the activation of Traf3/MAPK P38 pathway both in Aβ-induced BV-2 and HT22 cells. The effects of PELI1 overexpression on cell proliferation, apoptosis, and Traf3/MAPK P38 pathway were partly abrogated by miR-590-5p mimic both in BV-2 and HT22 cells. In conclusion, miR-590-5p was expressed at lower levels in AD, and miR-590-5p/PELI1 axis might be involved in the progression of AD by the downstream Traf3/MAPK P38 pathway.