Title : 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 cellular biochemist specializing in neurodegenerative diseases researches, their experimental models and outbreak response. She holds a PhD in Biochemistry from Novosibirsk Medical University. Dr. Korolenko has worked with Lysosomal Storage Diseases (experimental models) and has published extensively on reproduction of lysosomal storage syndromes in the experiment (hepatocytes, macrophages, neurons) and their prevention. She is currently the Professor of the Neurodegenerative Diseases study (Alzheimer disease) Program at the Scientific Research Institute of Neurosciences and Medicine, Novosibirsk, Russia.