Investigating neurotrophin genetics and hippocampal volume

As individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Relevance. The effect of a tissue engineering construct based on synthetic octacalcium phosphate activated with plasmid DNA with vascular endothelial growth factor gene on bone morphogenesis at the jaw defect sites of patients was studied. It is shown that the studied osteoplastic material stimulates osteosynthesis pathways already at early stages, and xenogenic hydroxyapatite, triggers osteogenesis processes with considerable delay and does not have time to form a full-fledged bone structure by 6 months.Aim. Evaluate the dynamics of reparative osteogenesis based on the results of histomorphometric diagnostics in patients with defects in the jaw bones of various configurations and lengths with an implanted bone matrix based on synthetic octacalcium phosphate activated with plasmid deoxyribonucleic acid with genes of vascular endothelial growth factor.Materials and methods. Histomorphological examination of bone tissue biopsy of jaws was carried out in 50 patients of both genders, who needed additional volume of bone tissue to install dental implantation. Patients were divided into 2 groups by type of grafted material. 6 months after the surgery, bone biopsies were taken from the bone sites at the stage of implant placement. Histomorphological patterns and histomycrophotograms were studied in bone biopcies.Results. In bone tissue biopsies of patients implanted with a tissue engineering construct based on synthetic octacalcium phosphate activated with plasmid DNA with vascular endothelial growth factor gene, it was revealed that after 6 months there was prevaluation of mature bone tissue (42,71%), with the proportion of differentiated plate bone tissue being < 90%.Conclusions. Histomorphometric analysis showed that in patients implanted with a tissue engineering construct based on synthetic octacalcium phosphate activated with plasmid DNA with vascular endothelial growth factor gene, after 6 months, early rearrangement of bone tissue into a mechanically dense and highly mineralized structure was detected.

Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice

Gene therapy is expected to be used for the treatment of peritoneal fibrosis, which is a serious problem associated with long-term peritoneal dialysis. Hepatocyte growth factor (HGF) is a well-known anti-fibrotic gene. We developed an ultrasound and nanobubble-mediated (sonoporation) gene transfection system, which selectively targets peritoneal tissues. Thus, we attempted to treat peritoneal fibrosis by sonoporation-based human HGF (hHGF) gene transfection in mice. To prepare a model of peritoneal fibrosis, mice were intraperitoneally injected with chlorhexidine digluconate. We evaluated the preventive and curative effects of sonoporation-based hHGF transfection by analyzing the following factors: hydroxyproline level, peritoneum thickness, and the peritoneal equilibration test. The transgene expression characteristics of sonoporation were also evaluated using multicolor deep imaging. In early-stage fibrosis in mice, transgene expression by sonoporation was observed in the submesothelial layer. Sonoporation-based hHGF transfection showed not only a preventive effect but also a curative effect for early-stage peritoneal fibrosis. Sonoporation-based hHGF transfection may be suitable for the treatment of peritoneal fibrosis regarding the transfection characteristics of transgene expression in the peritoneum under fibrosis.