INVESTIGADORES
SARAVIA Flavia Eugenia
artículos
Título:
Prominently decreased hippocampal neurogenesis in a spontaneous model of f type 1 diabetes, the nonobese diabetic mouse.
Autor/es:
BEAUQUIS J, SARAVIA F, COULAUD J, ROIG P, DARDENNE M, HOMO-DELARCHE F, DE NICOLA AF.
Revista:
EXPERIMENTAL NEUROLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2008 vol. 210 p. 359 - 367
ISSN:
0014-4886
Resumen:
Abstract
In human diabetes, degenerative and functional disorders of the central nervous system, including depression, are common findings. Defective
dentate gyrus (DG) neurogenesis is associated with affective-related disorders and depression. We previously demonstrated reduced DG
neurogenesis in a pharmacological type 1 diabetes model, the streptozotocin (STZ)-treated mouse. Here, we explored DG neurogenesis in a
spontaneous T1D model, the nonobese diabetic (NOD) mouse, at prediabetic and diabetic stages.
Cell proliferation was assessed in the DG of 5, 8 and 12-week-old control C57BL/6 and BALB/c strains and NOD mice, killed 2 h after
bromodeoxyuridine (BrdU) administration. Survival of the newly generated cells was studied in 15-week-old animals that were killed 21 days
after BrdU injection. The number of proliferative BrdU-positive cells in the DG was, regardless of age, constantly and significantly lower in NOD
than in control strains, showing the presence of hippocampal alterations far before clinical diabetes onset in NOD mice. Diabetes also strongly
decreased cell survival in NOD DG. However, cell phenotype proportion, as assessed by co-localization with neuronal or glial markers and
confocal microscopy, was not modified.
Hippocampal neurogenesis is strongly diminished in the spontaneous NOD model, like in the STZ model. Notably, NOD hippocampal DG cell
proliferation defect takes place during the prediabetic stage. Whether this early alteration might result, in this autoimmune strain, from
hypothalamo-pituitary adrenal axis alterations and/or ongoing brain inflammatory process sharing many characteristics of aging is discussed and
deserves further investigation.