Enhancement of Low-Intensity Pulsed Ultrasound on the Expression of Neurotrophic Factors in Glia Cells
Date Issued
2008
Date
2008
Author(s)
Chiang, Shih-Wei
Abstract
Low-intensity pulsed ultrasound (LIPUS) is regarded as a non-invasive and non-thermal mechanotransduction which accelerates fracture healing, promotes bone formation and tissues regeneration. However, the mechanism and effect generated by ultrasound (US) in central nervous system (CNS) is not clear. Astrocytes exert many functions, including the formation of the blood-brain barrier, the provision of nutrients to the nervous tissue, and play a principal role in the repair and scarring process in the brain. Astrocytes support neuronal cells by secreting various kinds of neurotrophic factors such as the glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Neurotrophic factors play several important roles in the survival and development of neuronal cells. Here, we explored the influence of US stimulation on astrocytes. It was found that US stimulation increased mRNA expression levels of GDNF, BDNF and VEGF in cultured rat brain astrocyte (RBA-1). Flow cytometry analysis demonstrated that US increased cell surface expression of α2 and β3 integrins. Rhodostomin, a snake venom disintegrin, attenuated the expression of neurotrophic factors induced by US. Phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin antagonized the potentiating action of US. NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also exerted similar inhibitory action on the effect of US. Furthermore, US stimulation increased the phosphorylation of Akt at Ser473 . US stimulation also induced phosphorylation of inhibitory subunitIκB) of nuclear factor-κB (NF-κB), phosphorylation of p65 and translocation of active p65 and p50 subunit from cytosol into the nucleus. It was also found that US stimulation increased mRNA expression levels of GDNF and BDNF in the hippocampus of Rats. Taken together, our results provide evidence that US stimulation increases GDNF, BDNF and VEGF expression via the integrin/PI3K/Akt and NF-κB signaling pathway. We also examined the effect of US on microglia by using BV-2 cell line. Exposure to hypoxia caused microglia activation and animal studies have shown that neuronal cell death is related to microglia activation following cerebral ischemia. Our preliminary results demonstrate that hypoxia induced iNOS and TNF-α expression in microglia. In addition, hypoxia-induced iNOS and TNF-α expression was attenuated by the pre-exposure to US. In conclusion, US enhanced neurotrophic factor release in astrocytes and inhibited iNOS and TNF-α production in hypoxic microglia. US may be thus helpful to the diseases of CNS.
Subjects
Ultrasound
Astrocytes
Microglia
neurotrophic factor
iNOS
Type
thesis
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