Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes.

REVSIN, Y.; SARAVIA, F.; ROIG, P.; LIMA, A.; DE KLOET, ER.; DE NICOLA, AF.

BRAIN RESEARCH

Año: 2005 vol. 1038 p. 22 - 31

0006-8993

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (non-obese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice with one month-old STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; b) abnormal expression of early gene products associated with neuronal activation and apoptosis, including a high number of Jun+ neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; c) augmented activity of NADPH-diaphorase, linked to nitric oxide (NO) production, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex. We suggest that the abnormalities of the diabetic brain have common features with aging, neurodegeneration and stress-related diseases.