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| Author(s): |
Igor Rafael Correia Rocha
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2023-05-23 |
| Examining board members: |
Marucia Chacur;
Maria Luiza de Morais Barreto de Chaves;
Adriano Polican Ciena;
Andréa da Silva Torrão
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| Advisor: | Marucia Chacur |
| Abstract | |
The primary cellular damage arising from Schwann cells in hyperglycemia is a largely overlooked aspect in terms of diabetic peripheral neuropathy (DPN). Furthermore, the mechanisms by which photobiostimulation (PBS) generates its promising effects is still a field of extensive investigation. Little is known about the mechanisms of PBS effects on DPN. The aim of this study was to investigate the mechanisms involved in antihyperalgesic / anti-inflammatory effects of PBS in rats with streptozotocin (STZ) induced DPN, as well as the effects of PBS Schwann cells respiration. The experiments were approved by the Animal Ethics Commission (CEUA/ICB-USP), protocol 2269190619. Male Wistar rats, 200-250 g, 4-8 weeks old, received a single dose of STZ (85 mg/kg) or vehicle (saline) intraperitoneally (i.p). Type I diabetes was determined by blood glucose 250 mg/dL. The animals were submitted to the electronic von Frey test 72 hours after the injection of STZ or vehicle (saline) and on days interspersed with the treatment with PBS. Hyperalgesic diabetic rats were submitted to PBS (AsGa, 904 nm; 6 J; 45 mW; 18 s) applied over the region of the sciatic nerve. Schwann cells were cultured in physiological and hyperglycemic glucose medium (5.5 and 55 mM) and from passage 3 onwards they were subjected to PBS (AsGa, 904 nm; 6 J; 45 mW; 18 s). The rats were euthanized and the sciatic nerve, dorsal root ganglia (DRG) and, additionally, spinal cord and anterior cingular cortex were collected for Western blot experiments. Schwann cells were subjected to MTT cell viability assays and cell respiration assays. PBS reversed mechanical hyperalgesia in DPN rats. PBS modulated pro and anti-inflammatory cytokines in the sciatic nerve and DRG of diabetic rats, as well as modulated the advanced glycation end product carboxymethyl lysine (CML) and its receptor (RAGE) in those tissues. It was also observed that PBS was able to modulate nuclear transcription factor kappa B (NFKB) in the sciatic nerve and DRG of diabetic rats. PBS significantly modulated mitochondrial fusion and fission processes in the sciatic nerve and DRG of diabetic rats. PBS also modulated proteins related to pain and excitation and inhibition processes in the central nervous system (spinal cord and anterior cingulate cortex) of diabetic rats. PBS increased Schwann cells viability as well as improved cellular respiration when in hyperglycemic medium (55 mM). These results may be influential for the development of new forms of complementary therapies aimed at restoring the peripheral nervous system in hyperglycemic conditions. (AU) | |
| FAPESP's process: | 17/25554-0 - Study of the effects of the photobiostimulation on the Schwann cell mitochondrial metabolism in Type 1 Diabetes Mellitus |
| Grantee: | Igor Rafael Correia Rocha |
| Support Opportunities: | Scholarships in Brazil - Doctorate |