Abstract：
:The present study has been designed to establish the potential benefits from 1-methylnicotinamide (MNA) treatment on brain disorders associated with type 1 diabetes. All experiments were carried out after 6 weeks of streptozotocin-induced diabetes (60 mg/kg of body weight, i.p.) in male Wistar rats treated for 5 weeks with or without MNA (100 mg/kg of body weight, per os in drinking water) after 1 week of diabetes induction. Diabetes was shown to reduce monoamine neurotransmitter serotonin transporters activity, as assessed by significant inhibition of [2-(14)C]serotonin uptake, that was accompanied by elevation of spontaneous mediator release in rat brain synaptosomes. Treatment with MNA slightly attenuated diabetes-induced changes in brain serotoninergic system. The precise mechanism underlying MNA action on central serotonin neurotransmission is not known, but appears to be linked to metabolic and signalling pathways involved in controlling synaptic function rather than being associated with direct modulation of serotonin transporters. In particular, MNA action was associated with its partial normalizing effects on such biochemical indices of neuropathy development as decrease in synaptosomal Na(+),K(+)-ATPase activity and plasma membrane depolarization of synaptic endings. Elevated sorbitol formation in brain and NAD(+) deficits resulted from diabetes as major metabolic imbalances were remarkably countered by MNA treatment. However, diabetes-induced decrease in cytosolic NAD(+) to NADH ratio in brain remained unchanged. Notably, MNA supplementation to diabetic rats caused a slight lowering effect on blood glucose level. Accordingly, our findings indicate that neuroprotective properties of MNA are linked to modulation of synaptic activity through multiple mechanisms. In conclusion, we suggest that 1-methylnicotinamide might be a useful agent for treating brain failures related to diabetes.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Kuchmerovska T,Shymanskyy I,Chlopicki S,Klimenko Adoi
10.1016/j.neuint.2009.10.004subject
Has Abstractpub_date
2010-01-01 00:00:00pages
221-8issue
2eissn
0197-0186issn
1872-9754pii
S0197-0186(09)00294-0journal_volume
56pub_type
杂志文章abstract：:The excitatory action of glutamate and aspartate upon direct application to the motor cortex of dogs was first reported in 1952 by Takashi Hayashi, Keio University School of Medicine, Tokyo. Although this investigation had been performed in the early 1940s during the Second World War, the publication in English was de...
journal_title：Neurochemistry international
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journal_title：Neurochemistry international
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pub_type： 杂志文章
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