A pathophysiological intersection between metabolic biomarkers and memory: a longitudinal study in STZ-induced diabetic mouse model

MariaTeresa Venuti ¹ Elisa Roda ² Federico Brandalise ³ Meghma Sarkar ¹ Mattia Cappelletti ⁴ Attilio Francesco Speciani ⁴ Irene Soffientini ¹ Erica Cecilia Priori ¹ Francesca Giammello ¹ Daniela Ratto ¹ Carlo Alessandro LOCATELLI ² Paola Rossi ^1*

• ¹ Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia, Pavia, Italy
• ² Istituti Clinici Scientifici Maugeri IRCCS, Milan, Milan, Lombardy, Italy
• ³ University of Milan, Milan, Lombardy, Italy
• ⁴ Independent researcher, Milano, Italy

Diabetes mellitus (DM) is a metabolic disorder characterized by high blood sugar levels due to insufficient insulin production or insulin resistance. Recently, metabolic biomarkers, such as glycated albumin (GA) and methylglyoxal (MGO), have been successfully employed for the management of diabetes and its complications. The main goal of this study was to investigate the relationship between metabolic parameters, related to diabetic conditions and, the recognition memory, a declarative episodic long-term memory in a streptozotocin (STZ)-induced diabetes mouse model. The longitudinal experimental plan scheduled five experimental time points, starting from 9 months and lasting until 19 months of mice age, and included different evaluations: (i) fasting serum glucose, glycated albumin (GA), and methylglyoxal (MGO), (ii) recognition memory performance; (iii) histological examinations of pancreas and hippocampus. At 13 months-old mice were randomly divided into two groups and STZ (50 mg/kg i.p.) or vehicle was administered for 5 consecutive days. Mice were fed with a normal diet but, starting from 14 months, half of them were watered with a high sugar (HS) drink to explore the potential detrimental effects of HS intake to hyperglycemia. Our main outcomes were: (i) HS intake alone does not contribute to worsened diabetic condition/hyperglycemia; (ii) GA emerges as a reliable biomarker for monitoring diabetes condition, consistently rising with hyperglycemia; (iii) diabetes condition correlates with a worsening of recognition memory; (iv) diabetic mice display mild to severe insulitis and injure hippocampal cytoarchitecture, detectable in Ammon's horns regions CA1 and CA3; (v) correlation among recovered normal fasting glycemia level and recognition memory, partial regaining of physiological pancreas morphology, and hippocampal cytoarchitecture. ha eliminato: sciences ha eliminato: Milan ha eliminato: Milano