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.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Beauquis J,Saravia F,Coulaud J,Roig P,Dardenne M,Homo-Delarche F,De Nicola Adoi
10.1016/j.expneurol.2007.11.009subject
Has Abstractpub_date
2008-04-01 00:00:00pages
359-67issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(07)00423-2journal_volume
210pub_type
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journal_title：Experimental neurology
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