Differential impact of diabetes and hypertension in the brain: adverse effects in white matter

Neurobiol Dis. 2011 Jun;42(3):446-58. doi: 10.1016/j.nbd.2011.02.007. Epub 2011 Feb 13.


Humans subjected to diabetes mellitus (DM) and/or hypertension (HTN) develop cognitive decline, cerebral atrophy and white matter abnormalities, but the relative effects of DM and HTN upon myelin and axonal integrity is unknown. We studied models of Type 1 (streptozotocin-induced) and Type 2 DM (ZDF) ± HTN (ZSF-1, SHR) in adult rats using magnetic resonance imaging (MRI) and structural and molecular techniques. Type 1 or 2 DM independently led to loss of myelin associated with changes with MRI T2 and magnetization tensor ratios throughout white matter regions. HTN's effect on myelin loss was minimal. Loss of oligodendroglia and myelin proteins was only identified in either Type 1 or Type 2 DM. Activation of the signal transduction pathways initiated by the receptor for advanced glycation end products (AGEs), RAGE, including upregulation of the signal transducer nuclear factor (NF) κB only occurred with DM. Diabetes is a greater contributor to white matter loss than hypertension in the rat brain, while hypertension only plays a mild additive effect upon neurodegeneration in the presence of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Glucose
  • Blotting, Western
  • Brain / metabolism
  • Brain / pathology*
  • Brain Mapping
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Electrophoretic Mobility Shift Assay
  • Glycation End Products, Advanced / metabolism
  • Hypertension / metabolism
  • Hypertension / pathology*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Myelin Basic Protein / metabolism
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology*
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction


  • Blood Glucose
  • Glycation End Products, Advanced
  • Myelin Basic Protein