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Zinc regulation of adult stem cell proliferation and neurogenesis in the rat dentate gyrus
Author(s) -
Tassabehji Nadine M.,
Somers Rikki C.,
Reiter Allison,
Alshingiti Almamoun,
Levenson Cathy W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a985-d
Subject(s) - dentate gyrus , neurogenesis , neun , endocrinology , antidepressant , medicine , behavioural despair test , hippocampus , hippocampal formation , zinc deficiency (plant disorder) , fluoxetine , zinc , chemistry , psychology , serotonin , neuroscience , immunohistochemistry , receptor , organic chemistry
Dietary zinc deficiency leads to the development of depression‐ and anxiety‐like behaviors in adult rats. Zinc deficient (ZD) rats displayed anorexia, anhedonia (reduced saccharin:water intake, p<0.001), and decreased exploratory behavior in a light‐dark box test (p<0.05). The antidepressant drug fluoxetine (10mg/kg body wt), a selective serotonin reuptake inhibitor (SSRI), reduced behavioral despair, as measured by the forced swim test, in zinc adequate (ZA), but not ZD rats (p<0.002). Thus, it appears that ZD not only induces depression, but also impairs the efficacy of antidepressant drugs. Because it is known that fluoxetine action is dependent on stem cell proliferation in the dentate gyrus of the adult hippocampus, we hypothesized that low zinc status impairs proliferation in this region of the limbic system. Following 3 wk of zinc‐adequate (ZA, 30 ppm), zinc‐deficient (ZD, 1 ppm), pair‐fed (PF, 30 ppm), or zinc‐supplemented (ZS, 100 ppm) diets, immunohistochemistry was used to quantify the number of Ki67 positive cells as a measure of newly proliferated cells in the dentate. Neurogenesis was determined by the co‐localization of the early neuronal marker, NeuN, with Ki67. Zinc deficiency reduced the number of Ki67 positive cells to 25% of ZA controls (p<0.05). Furthermore, the ZS diet appeared to increase neuronal differentiation. Together, these data suggest that ZD impairs neurogenesis and neuroplasticity in the dentate leading to behaviors consistent with depression in adult rats, and limiting the efficacy of antidepressant drugs. Supported by Susan E. Lucas Neuroscience Fellowship.