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|Title:||STUDIES ON DIABETIC PERIPHERAL NEUROPATHY IN THE DB/DB, TYPE 2 DIABETES MOUSE||Authors:||NYEIN NYEIN THAW DAR||Keywords:||Diabetes, Peripheral neuropathy, Mouse model, db/db mice, Nerve conduction study, Behavioral test||Issue Date:||4-Aug-2011||Citation:||NYEIN NYEIN THAW DAR (2011-08-04). STUDIES ON DIABETIC PERIPHERAL NEUROPATHY IN THE DB/DB, TYPE 2 DIABETES MOUSE. ScholarBank@NUS Repository.||Abstract:||In diabetes, many organs and systems develop serious complications, among which diabetic peripheral neuropathy (DPN) is one of the most common. The pathogenesis is still uncertain, and the appropriate choice of experimental models is fundamental in studying this complication. The BKS.Cg-m+/+Leprdb/J (BKS-db/db) type 2 diabetes mouse model has been used commonly since the 1970s. However, the time progression of sequential changes in the peripheral nerves of the db/db model has not been well-defined. We studied the sequential sensorimotor changes in db/db mice from 6 weeks to 26 weeks of age. Nerve conduction velocity (CV), behavioral tail flick and hind paw withdrawal tests were performed. We found that sensory CV delay was detectable at 10 weeks of age, compared to motor CV delay, which was detectable only at 14-16 weeks and varied considerably compared to the sensory CV. We also observed that the peripheral nerve CV increased steadily in non-diabetic controls with age (up to 26 weeks) but in db/db mice, there was no further absolute increase in CV after 6 weeks. There was significant increase in latency in the paw withdrawal response from 6 weeks onwards (P<0.001) but increased latency in tail flick response was detected only from 22 weeks onwards (P<0.05). Therefore, our study indicated that electrophysiological studies may be more consistent and useful as an early diagnostic tool to detect the peripheral neuropathy compared to behavioral tests of reflexes. The only effective treatment for peripheral neuropathy is good blood glucose control. In this study, we evaluated the therapeutic option of cell therapy for early DPN in our mouse model. Our earlier study had shown that the sensory system was more suitable as changes were present consistently at 10 weeks. Therefore, we mainly focused on the sensory system in this part of the study and studied the effect of cell therapy from 14 to 22 weeks. There was no significant improvement in the cell treated diabetic mice compared to the saline treated diabetic mice. Direct transplantation of freshly prepared bone marrow cells into diabetic mice was not successful in the treatment of diabetic peripheral neuropathy in db/db mice. Further investigations will be needed, and may include more processing of the bone marrow populations in order to obtain purer stem cell populations. In conclusion, our study demonstrated that sensory nerve impairment was demonstrable consistently from 10 weeks of age but motor impairment was more variable and demonstrable only at 14-16 weeks of age. In control healthy mice, there was an increase in nerve CV as they grew older but this increase was absent in diabetic mice. This study presents novel information on the development time course on peripheral nerve CV impairment in the db/db mouse model, demonstrating a time difference between sensory and motor CV impairment. This may be important in further studies on the early pathogenesis and early therapeutic intervention in DPN using this mouse model. Further investigations are needed to shed light on cell therapy in diabetic peripheral neuropathy.||URI:||http://scholarbank.nus.edu.sg/handle/10635/30063|
|Appears in Collections:||Master's Theses (Open)|
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