Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes.
The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese 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 1 month after 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, 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 oxidative stress, 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.
Revsin
Yanina
Y
Laboratory of Neuroendocrine Biochemistry, Institute of Biology and Experimental Medicine, Obligado 2490 (1428) Buenos Aires, Argentina.
Saravia
Flavia
F
Roig
Paulina
P
Lima
Analia
A
de Kloet
E Ronald
ER
Homo-Delarche
Francoise
F
De Nicola
Alejandro F
AF
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013311:Streptozocin
D001057:Apolipoproteins E; D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013311:Streptozocin; D009252:NADPH Dehydrogenase