Methyl Donor Supplementation Prevents a Folate Deficiency-induced Depression-like State and Neuronal Immaturity of the Dentate Gyrus in Mice.

We have recently shown that folate deficiency induces depression-like behavior and neuronal immaturity in the dentate gyrus (DG) in mice. We also revealed that folate deficiency inhibits neuronal maturation, hypomethylates the promoter of certain neuronal genes and decreases intracellular levels of S-adenosylmethionine (SAM), a methyl donor, in cultured neural stem and progenitor cells. Based on these findings, we hypothesized that SAM reduction may be involved in a folate deficiency-induced depressive state and neural immaturity.

Kihito prevents corticosterone-induced brain dysfunctions in mice.

Kihito (KIT; Gui Pi Tang) is a traditional herbal medicine that is used for treatment of neuropsychiatric disorders such as depression, anxiety, neurosis and insomnia in China and Japan. Recently, it has also been shown that KIT improves cognitive dysfunction in patients with Alzheimer's disease. In this study, to investigate the mechanisms underlying the effects of KIT on stress-induced brain dysfunctions such as a depressed state and memory impairment, we examined whether KIT prevents behavioral and neurophysiological abnormalities in mice treated chronically with corticosterone (CORT).

Low folate induces abnormal neuronal maturation and DNA hypomethylation of neuronal differentiation-related genes in cultured mouse neural stem and progenitor cells.

Folate deficiency in a fetus is well known to cause neurodevelopment defects and development disorders. A low level of folate is also thought to be a risk for depression in adults. We have previously shown that post-weaning low folate induces neuronal immaturity in the dentate gyrus in mice, which suggests that low folate causes neuropsychological disorders via inhibition of neuronal maturation.

Ferulic acid alleviates abnormal behaviors in isolation-reared mice via 5-HT receptor partial agonist activity.

Rationale: Preclinical and clinical reports suggest that ferulic acid (FA), a plant-derived phenylpropanoid, is effective against mental health problems such as agitation, anxiety, and irritability in humans, without causing adverse side effects. However, the mechanism of action is unknown.

Objective: The aim of the study is to investigate the mechanism underlying the ameliorative effects of FA on mental health problems such as agitation, anxiety, and irritability, using in vivo behavioral analysis, in vitro pharmacological analysis, and in silico binding analysis.