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1.
J Steroid Biochem Mol Biol ; 231: 106313, 2023 07.
Article in English | MEDLINE | ID: mdl-37075986

ABSTRACT

Depression is a common mental disorder with an increasing incidence. Several studies have demonstrated that cortical DNA hypomethylation is associated with depression-like behaviors. This study aims to investigate whether maternal vitamin D deficiency (VDD) induces depression-like behaviors and to explore the effects of folic acid supplement on VDD-induced cortical DNA hypomethylation in adult offspring. Female mice were fed with a VDD diet, beginning at 5 weeks of age and throughout pregnancy. Depression-like behaviors were evaluated, and cortical 5-methylcytosine (5mC) content was detected in adult offspring. Results showed that depression-like behaviors were observed in adult offspring of the VDD group. Cortical Ache and Oxtr mRNAs were upregulated in female offspring of the VDD group. Cortical Cpt1a and Htr1b mRNAs were increased in male offspring of the VDD group. Moreover, cortical 5mC content was reduced in offspring of VDD-fed dams. The additional experiment showed that serum folate and cortical S-adenosylmethionine (SAM) contents were decreased in the offspring of the VDD group. Folic acid supplement attenuated VDD-induced SAM depletion and reversed cortical DNA methylation. Moreover, folic acid supplement attenuated VDD-induced upregulation of depression-related genes. In addition, folic acid supplement alleviated maternal VDD-induced depression-like behaviors in adult offspring. These results suggest that maternal VDD induces depression-like behavior in adult offspring by reducing cortical DNA methylation. The gestational folic acid supplement prevents VDD-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring.


Subject(s)
Folic Acid , Vitamin D Deficiency , Pregnancy , Animals , Male , Female , Mice , Folic Acid/pharmacology , DNA Methylation , Depression/etiology , Depression/prevention & control , DNA
2.
Int J Mol Med ; 48(1)2021 07.
Article in English | MEDLINE | ID: mdl-33955518

ABSTRACT

Women experience cognitive decline as they age due to the decrease in estrogen levels following menopause. Currently, effective pharmaceutical treatments for age­related cognitive decline are lacking; however, several Traditional Chinese medicines have shown promising effects. Lycium barbarum polysaccharides (LBPs) were found to exert a wide variety of biological activities, including anti­inflammatory, antioxidant and anti­aging effects. However, to the best of our knowledge, the neuroprotective actions of LBP on cognitive impairment induced by decreased levels of estrogen have not yet been determined. To evaluate the effects of LBP on learning and memory impairment in an animal model of menopause, 45 female ICR mice were randomly divided into the following three groups: i) Sham; ii) ovariectomy (OVX); and iii) OVX + LBP treatment. The results of open­field and novel object recognition tests revealed that mice in the OVX group had learning and memory impairments, and lacked the ability to recognize and remember new objects. Notably, these deficits were attenuated following LBP treatment. Immunohistochemical staining confirmed the protective effects of LBP on hippocampal neurons following OVX. To further investigate the underlying mechanism of OVX in mice, mRNA sequencing of the hippocampal tissue was performed, which revealed that the Toll­like receptor 4 (TLR4) inflammatory signaling pathway was significantly upregulated in the OVX group. Moreover, reverse transcription­quantitative PCR and immunohistochemical staining demonstrated that OVX induced hippocampal injury, upregulated the expression levels of TLR4, myeloid differentiation factor 88 and NF­κB, and increased the expression of TNF­α, IL­6 and IL­1ß inflammatory factors. Conversely, LBP treatment downregulated the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, decreased the inflammatory response and reduced neuronal injury in mice that underwent OVX. In conclusion, the findings of the present study indicated that oral LBP treatment may alleviate OVX­induced cognitive impairments by downregulating the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, thereby reducing neuroinflammation and damage to the hippocampal neurons. Thus, LBP may represent a potential agent for the prevention of learning and memory impairments in patients with accelerated aging caused by estrogen deficiency.


Subject(s)
Aging/drug effects , Drugs, Chinese Herbal/pharmacology , Memory Disorders/drug therapy , Neurocognitive Disorders/drug therapy , Signal Transduction/drug effects , Administration, Oral , Animals , Female , Gene Expression Regulation , Hippocampus/drug effects , Learning/drug effects , Medicine, Chinese Traditional , Mice , Mice, Inbred ICR , NF-kappa B/genetics , NF-kappa B/metabolism , Neuroinflammatory Diseases/drug therapy , Neurons/drug effects , Ovariectomy/adverse effects , Random Allocation , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
3.
Mol Med Rep ; 17(3): 4515-4523, 2018 03.
Article in English | MEDLINE | ID: mdl-29344669

ABSTRACT

Oligodendrocytes (OLs) are myelin-forming cells that are present within the central nervous system. Impaired oligodendrocyte precursor cell (OPC) differentiation into mature OLs is a major cause of demyelination diseases. Therefore, identifying the underlying molecular mechanisms of OPC differentiation is crucial to understand the processes of myelination and demyelination. It has been acknowledged that various extrinsic and intrinsic factors are involved in the control of OPC differentiation; however, the function of ion channels, particularly the voltage­gated chloride channel (CLC), in OPC differentiation and myelination are not fully understood. The present study demonstrated that CLC­2 may be a positive modulator of OPC differentiation and myelination. Western blotting results revealed that CLC­2 was expressed in both OPCs and OLs. Furthermore, CLC­2 currents (ICLC­2) were recorded in both types of cells. The inhibition of ICLC­2 by GaTx2, a blocker of CLC­2, was demonstrated to be higher in OPCs compared with OLs, indicating that CLC­2 may serve a role in OL differentiation. The results of western blotting and immunofluorescence staining also demonstrated that the expression levels of myelin basic protein were reduced following GaTx2 treatment, indicating that the differentiation of OPCs into OLs was inhibited following CLC­2 inhibition. In addition, following western blot analysis, it was also demonstrated that the protein expression of the myelin proteins yin yang 1, myelin regulatory factor, Smad­interacting protein 1 and sex­determining region Y­box 10 were regulated by CLC­2 inhibition. Taken together, the results of the present study indicate that CLC­2 may be a positive regulator of OPC differentiation and able to contribute to myelin formation and repair in myelin­associated diseases by controlling the number and open state of CLC-2 channels.


Subject(s)
Cell Differentiation , Myelin Sheath/metabolism , Action Potentials/drug effects , Animals , CLC-2 Chloride Channels , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chloride Channels/antagonists & inhibitors , Chloride Channels/metabolism , Ki-67 Antigen/metabolism , Oligodendrocyte Precursor Cells/cytology , Oligodendrocyte Precursor Cells/metabolism , Oligodendroglia/cytology , Oligodendroglia/metabolism , Rats , Scorpion Venoms/pharmacology , Transcription Factors/metabolism
4.
Dev Cell ; 27(1): 113-22, 2013 Oct 14.
Article in English | MEDLINE | ID: mdl-24094741

ABSTRACT

Indole-3-acetic acid (IAA), the natural auxin in plants, regulates many aspects of plant growth and development. Extensive analyses have elucidated the components of auxin biosynthesis, transport, and signaling, but the physiological roles and molecular mechanisms of auxin degradation remain elusive. Here, we demonstrate that the dioxygenase for auxin oxidation (DAO) gene, encoding a putative 2-oxoglutarate-dependent-Fe (II) dioxygenase, is essential for anther dehiscence, pollen fertility, and seed initiation in rice. Rice mutant lines lacking a functional DAO display increased levels of free IAA in anthers and ovaries. Furthermore, exogenous application of IAA or overexpression of the auxin biosynthesis gene OsYUCCA1 phenocopies the dao mutants. We show that recombinant DAO converts the active IAA into biologically inactive 2-oxoindole-3-acetic acid (OxIAA) in vitro. Collectively, these data support a key role of DAO in auxin catabolism and maintenance of auxin homeostasis central to plant reproductive development.


Subject(s)
Dioxygenases/metabolism , Indoleacetic Acids/metabolism , Oryza/enzymology , Plant Infertility/genetics , Plant Proteins/metabolism , Dioxygenases/genetics , Homeostasis , Mutation , Oryza/physiology , Plant Proteins/genetics , Pollen/physiology , Pollination/genetics
5.
J Agric Food Chem ; 58(22): 11553-60, 2010 Nov 24.
Article in English | MEDLINE | ID: mdl-20961040

ABSTRACT

This study presents new sample preparation and analytical procedures for the quantification of pesticides on processed tea leaves. The new method includes tea extraction and dispersive solid phase extraction (d-SPE) to prepare gas chromatography (GC) and ultrahigh-performance liquid chromatography (UHPLC)-ready samples, providing a fast and cost-effective solution for time-sensitive industrial analysis to fulfill regulatory requirements. Both GC-negative chemical ionization mass spectrometry (GC-NCI-MS) and UHPLC-tandem mass spectrometry (UHPLC-MS/MS) were employed to produce highly sensitive and reproducible data. Excellent limits of detection (typically below 1 µg/kg for GC and 10 µg/kg for UHPLC), wide linearity ranges, and good recoveries (mostly >70%) were achieved on the selected pesticides. Twenty-seven tea samples purchased from local grocery stores were analyzed using the newly developed methods. Among the pesticides analyzed, endosulfan sulfate and kelthane were the most frequently detected by GC-NCI-MS and imidacloprid and acetamiprid by UHPLC-MS/MS in these teas. The samples were found to be relatively clean, with <1 mg/kg of total pesticide residues. The organic-labeled teas were significantly cleaner than nonorganic ones. The cost per gram of tea did not correlate with pesticide residue levels detected.


Subject(s)
Camellia sinensis/chemistry , Chromatography, High Pressure Liquid/methods , Gas Chromatography-Mass Spectrometry/methods , Pesticide Residues/analysis , Solid Phase Extraction/methods , Tandem Mass Spectrometry/methods , Tea/chemistry , Pesticide Residues/isolation & purification
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