Diabetes and Cognitive Decline: An Innovative Approach\nto Analyzing the Biophysical and Vibrational Properties of the Hippocampus

Diabetes Mellitus\n(DM) is a disease characterized by high blood\nglucose levels, known as hyperglycemia. Diabetes represents a risk\nfactor for the development of neurodegenerative diseases, such as\nAlzheimer’s Disease (AD), one of the most prevalent neurodegenerative\ndiseases worldwide, which leads to progressive mental, behavioral,\nand functional decline, affecting many brain structures, especially\nthe hippocampus. Here, we aim to characterize the ultrastructural,\nnanomechanical, and vibrational changes in hyperglycemic hippocampal\ntissue using atomic force microscopy (AFM) and Raman spectroscopy.\nDM was induced in rats by streptozotocin injection (type 1) or dietary\nintervention (type 2). Cryosections of the hippocampus were prepared\nand analyzed on an MM8 AFM (Bruker) in Peak Force Quantitative Nanomechanics\nmode, performing 25 μm<sup>2</sup> scans in 9 regions of 3 samples\nfrom each group. Ultrastructural and nanomechanical data such as surface\nroughness, area, volume, Young’s modulus, and adhesion were\nevaluated. The hippocampal samples were also analyzed on a T64000\nSpectrometer (Horiba), using a laser λ = 632.8 nm, and for each\nsample, four spectra were obtained in different regions. AFM analyses\nshow changes on the ultrastructural scale since diabetic animals had\nhippocampal tissue with greater roughness and volume. Meanwhile, diabetic\ntissues had decreased adhesion and Young’s modulus compared\nto control tissues. These were corroboratedby Raman data that shows\nchanges in the molecular composition of diabetic tissues. The individual\nspectra show that the most significant changes are in the amide, cholesterol,\nand lipid bands. Overall, the data presented here show that hyperglycemia\ninduces biophysical alterations in the hippocampal tissue of diabetic\nrats, providing novel biophysical and vibrational cues on the relationship\nbetween hyperglycemia and dementia.