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

Diabetes mellitus types 1 and 2 (DM1 and DM2) and/or hypertension (HTN) can contribute to cognitive decline, cerebral atrophy and white matter abnormalities in humans. Adult rat models of streptozotocin-induced DM1 and genetic strains of DM2 and HTN were used to investigate relative contributions of DM and HTN for alterations in cerebral structure and function as well as insulin receptor biology using cognitive testing, magnetic resonance imaging (MRI), and histological and molecular methods. The effects of DM1 or DM2 were generally similar. DM was associated with earlier onset of cognitive impairment than with HTN alone. DM was independently correlated with brain atrophy, whereas HTN had minimal effects on brain volume. The combination of DM and HTN led to identifiable mild hippocampal neuronal loss while either DM or HTN led to synaptic loss. Only DM led to downregulation of the insulin receptor pathways' activation. In contrast, only HTN was associated with vascular luminal reduction and restricted cerebral perfusion on MRI. The impacts of DM and HTN in the brain differ, while their separate contributions can lead to some additive adverse effects within rodent brain grey matter.

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

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.