Post-weaning folate deficiency induces a depression-like state via neuronal immaturity of the dentate gyrus in mice

Folate deficiency has been suggested as a risk factor for depression in preclinical and clinical studies. Several hypotheses of mechanisms underlying folate deficiency-induced depressive symptoms have been proposed, but the detailed mechanisms are still unclear. In this study, we assessed whether po...

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Main Authors: Shoji Nishida (Author), Ryota Araki (Author), Akihiro Baba (Author), Sota Asari (Author), Shin Tachibana (Author), Yuki Nakajima (Author), Arimi Iwakumo (Author), Takeshi Yabe (Author)
Format: Book
Published: Elsevier, 2020-06-01T00:00:00Z.
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Summary:Folate deficiency has been suggested as a risk factor for depression in preclinical and clinical studies. Several hypotheses of mechanisms underlying folate deficiency-induced depressive symptoms have been proposed, but the detailed mechanisms are still unclear. In this study, we assessed whether post-weaning folate deficiency affect neurological and psychological function. The low folate diet-fed mice showed depression-like behavior in the forced swim test. In contrast, spontaneous locomotor activity, social behavior, coordinated motor skills, anxiety-like behavior and spatial memory did not differ between control and low folate diet-fed mice. In the dentate gyrus (DG) of the hippocampus, decreased number of newborn mature neurons and increased number of immature neurons were observed in low folate diet-fed mice. Staining with Golgi-Cox method revealed that dendritic complexity, spine density and the number of mature spines of neurons were markedly reduced in the DG of low folate diet-fed mice. Stress response of neurons indicated as c-Fos expression was also reduced in the DG of low folate diet-fed mice. These results suggest that reduction in the degree of maturation of newborn hippocampal neurons underlies folate deficiency-induced depressive symptoms.
Item Description:1347-8613
10.1016/j.jphs.2020.02.007