Abstract
Adult hippocampal neurogenesis (AHN) in the dentate gyrus is known to respond to environmental enrichment, chronic stress, and many other factors. The function of AHN may vary across the septo-temporal axis of the hippocampus, as different subdivisions are responsible for different functions. The dorsal pole regulates cognitive-related behaviors, while the ventral pole mediates mood-related responses through the hypothalamic-pituitary-adrenal (HPA) axis. In this study, we investigate different methods of quantifying the effect of environmental enrichment on AHN in the dorsal and ventral parts of the dentate gyrus (dDG and vDG). To this purpose, 11-week-old female CD-1 mice were assigned for 8 days to one of two conditions: the Environmental Enrichment (E) group received (i) running wheels, (ii) larger cages, (iii) plastic tunnels, and (iv) bedding with male urine, while the Control (C) group received standard housing. Dorsal CA (Cornu Ammonis) and DG regions were larger in the E than the C animals. Distance run linearly predicted the volume of the dorsal hippocampus, as well as of the intermediate and ventral CA regions. In the dDG, the amount of Doublecortin (DCX) immunoreactivity was significantly higher in E than in C mice. Surprisingly, this pattern was the opposite in the vDG (C > E). Real-time PCR measurement of Dcx mRNA and DCX protein analysis using ELISA showed the same pattern. Brain Derived Neurotrophic Factor (BDNF) immunoreactivity and mRNA displayed no difference between E and C, suggesting that upregulation of DCX was not caused by changes in BDNF levels. BDNF levels were higher in vDG than in dDG, as measured by both methods. Bdnf expression in vDG correlated positively with the distance run by individual E mice. The similarity in the patterns of immunoreactivity, mRNA and protein for differential DCX expression and for BDNF distribution suggests that the latter two methods might be effective tools for more rapid quantification of AHN.
Highlights
The hippocampus is a well-defined neuroanatomical structure in mammals, which includes two major subdivisions: the Dentate Gyrus (DG) and Ammon’s horn (Latin: Cornu Ammonis—CA), the latter being subdivided into different subfields (CA1, CA2, and CA3; Andersen, 2007)
Morphological Quantification Significantly more DCX immunoreactivity was detected in dorsal DG (dDG) than in ventral DG (vDG) [χ2(1) = 5.370, p = 0.020] and this effect was more pronounced in the experimental group [Figures 3A–G; enrichment∗region: χ2(1) = 14.838, p < 0.001]
When we entered the distance run by enriched animals as a covariate in the Generalized Estimating Equations (GEE) to correlate with DCX immunoreactivity, we found that this had no effect [Figure 3H; distance: χ2(1) = 1.792, p = 0.181] in either dDG (r2 = 0.027) or vDG [r2 = 0.030; region*distance: χ2(1) = 0.058, p = 0.810]
Summary
The hippocampus is a well-defined neuroanatomical structure in mammals, which includes two major subdivisions: the Dentate Gyrus (DG) and Ammon’s horn (Latin: Cornu Ammonis—CA), the latter being subdivided into different subfields (CA1, CA2, and CA3; Andersen, 2007). Consistent with this, the mechanism of many ( not all) antidepressant drugs to re-establish normal behavior in animal models of depression involves an increase in neurogenesis in the vDG (Santarelli et al, 2003; Boldrini et al, 2009; Tanti and Belzung, 2013a,b). This regional specificity of the AHN response does, depend on the exact conditions of the study (Wu and Hen, 2014)
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