Lysosomes, autophagy in brain cells of db/db mice with experimental diabetes

Lysosomes, autophagy in brain cells of db/db mice with genetic model of diabetes. Diabetes T2 is connected with forming of neurodegeneration development, especially in ageing. These changes include some symptoms of Alzheimer disease (AD), mechanism of their development were not studied until now, as well as their prevention. It was shown that the common mechanism of brain cells damage can be autophagy decreasing, which can be potential target for therapy. So, we used autophagy inductor trehalose to prevent and restore autophagy changes in experimental model of diabetes T2 – db/db mice of 5 months old (genetic model of diabetes). Db/db mice were characterize also by obesity, typical symptom for human diabetes. Trehalose as 3% water solution was used during 30 days, mice had free to food and drink ad libidum. Earlier we have shown that treatment of young db/db mice by disaccharide trehalose activated autophagy in liver by m-TOR-independent mechanism. In these experiments we have shown that trehalose treatment decreased obesity, hyperglycemia, decreased neuroinflammation and oxidative stress, restoring partially cognitive disturbances. The aim of our work was to study brain cells (neurons and glial cells) ultrastructural changes and autophagy gene expression (Atg8, Becn1, Park2) in brain cells was studied. In neurons and glial cells of db/db mice there was increased amount of lipofuscin (pigment of ageing), trehalose treatment did not influence significantly on this process. Trehalose treatment was not followed by activation of autophagy transcription genes; decreased expression of insulin gene expression (Insr) has been shown. Different effect of trehalose drinking was shown in young db/db mice (2 months old) compared to old db/db mice, which related possibly with ageing process.

Dr. Tatiana Korolenko is a Biochemist, graduated from Novosibirsk Medical Institute. She holds a PhD (candidate dissertation) in the Moscow Institute of Psychiatry, and doctoral dissertation in Novosibirsk Medical Institute. She was working in Central Research Laboratory of Novosibirsk Medical Institute as biochemist. Her research was devoted to study of lysosomes in liver pathology and lysosomotropic drugs. Currently she is principal scientific research worker, Professor in the Scientific Research Institute of Neuroscience and Medicine, Novosibirsk, had in general 14 aspirants and one doctorant.