Publications by authors named "Jin-Hua Fan"

4 Publications

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Fluoxetine Promotes Hippocampal Oligodendrocyte Maturation and Delays Learning and Memory Decline in APP/PS1 Mice.

Front Aging Neurosci 2020 13;12:627362. Epub 2021 Jan 13.

Department of Histology and Embryology, Chongqing Medical University, Chongqing, China.

Oligodendrogenesis dysfunction impairs memory consolidation in adult mice, and an oligodendrocyte abnormality is an important change occurring in Alzheimer's disease (AD). While fluoxetine (FLX) is known to delay memory decline in AD models, its effects on hippocampal oligodendrogenesis are unclear. Here, we subjected 8-month-old male amyloid precursor protein (APP)/presenilin 1 (PS1) mice to the FLX intervention for 2 months. Their exploratory behaviors and general activities in a novel environment, spatial learning and memory and working and reference memory were assessed using the open-field test, Morris water maze, and Y maze. Furthermore, changes in hippocampal oligodendrogenesis were investigated using stereology, immunohistochemistry, immunofluorescence staining, and Western blotting techniques. FLX delayed declines in the spatial learning and memory, as well as the working and reference memory of APP/PS1 mice. In addition, APP/PS1 mice exhibited immature hippocampal oligodendrogenesis, and FLX increased the numbers of 2'3'cyclic nucleotide 3'-phosphodiesterase (CNPase) and newborn CNPase oligodendrocytes in the hippocampi of APP/PS1 mice. Moreover, FLX increased the density of SRY-related HMG-box 10 protein (SOX10) cells and reduced the percentage of oligodendrocyte lineage cells displaying the senescence phenotype (CDKN2A/p16INK4a) in the hippocampus of APP/PS1 mice. Moreover, FLX had no effect on the serotonin (5-HT) 1A receptor (5-HT1AR) content or number of 5-HT1AR oligodendrocytes, but it reduced the content and activity of glycogen synthase kinase 3β (GSK3β) in the hippocampus of APP/PS1 transgenic mice. Taken together, FLX delays the senescence of oligodendrocyte lineage cells and promotes oligodendrocyte maturation in the hippocampus of APP/PS1 mice. FLX may regulate GSK3β through a mechanism other than 5-HT1AR and then inhibit the negative effect of GSK3β on oligodendrocyte maturation in the hippocampus of an AD mouse model.
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http://dx.doi.org/10.3389/fnagi.2020.627362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838348PMC
January 2021

Fluoxetine delays the cognitive function decline and synaptic changes in a transgenic mouse model of early Alzheimer's disease.

J Comp Neurol 2019 06 25;527(8):1378-1387. Epub 2019 Jan 25.

Department of Histology and Embryology, Chongqing Medical University, Chongqing, China.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline. Previous studies have reported that the syndrome of AD begins with subtle alterations in hippocampal synapses prior to frank neuronal degeneration. It has recently been reported that fluoxetine (FLX) shows positive effects on AD patients who have depression and anxiety. However, it is unclear whether FLX can affect the pathogenesis of AD mice in the early stage of AD. To address this question, 8-month-old male APP/PS1 double-transgenic AD mice were administered a 10-week course of FLX (10 mg/kg/day) injections. Then, spatial learning and memory were evaluated using a Morris water maze test. Immunohistological staining and an unbiased stereological method were used to estimate the total number of dendritic spine synapses in the hippocampus. We found that FLX significantly shortened the mean escape latencies of the 10-month-old mice; reduced the elevated levels of soluble Aβ40, Aβ42, and amyloid plaques in the hippocampus; and prevented the decrease in dendritic spine synapses and in postsynaptic protein PSD-95 density in the dentate gyrus, CA1/2 and CA3 regions of the hippocampus. Our results indicate that reversing synaptic impairment might be considered a promising therapeutic approach for alleviating the cognitive deficits associated with early AD. Moreover, our results suggest that FLX may be a safe and effective drug for delaying the progress of AD, which might provide a starting point for further research into new preventative measures and treatments for AD.
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http://dx.doi.org/10.1002/cne.24616DOI Listing
June 2019

Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury.

Drug Des Devel Ther 2016 24;10:1743-51. Epub 2016 May 24.

Department of Gastroenterology, Qilu Hospital, Shandong University, Ji'nan, Shandong Province, People's Republic of China.

Background: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.

Purpose: To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis.

Methods: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting.

Results: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse transcription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats.

Conclusion: SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway.
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http://dx.doi.org/10.2147/DDDT.S107679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887069PMC
May 2017

Identification of Candidate Genes for Seed Glucosinolate Content Using Association Mapping in Brassica napus L.

Genes (Basel) 2015 Nov 18;6(4):1215-29. Epub 2015 Nov 18.

Chongqing Engineering Research Center for Rapeseed, College of Agronomy and Biotechnology, Southwest University, Tiansheng Road 2, Beibei, Chongqing 400716, China.

Rapeseed contains glucosinolates, a toxic group of sulfur-containing glucosides, which play critical roles in defense against herbivores and microbes. However, the presence of glucosinolates in rapeseed reduces the value of the meal as feed for livestock. We performed association mapping of seed glucosinolate (GS) content using the 60K Brassica Infinium single nucleotide polymorphism (SNP) array in 520 oilseed rape accessions. A total of 11 peak SNPs significantly associated with GS content were detected in growing seasons of 2013 and 2014 and were located on B. napus chromosomes A08, A09, C03, and C09, respectively. Two associated regions of GS content covered by these markers were further verified, and three B. napus homologous genes involved in the biosynthesis and accumulation of GS were identified. These genes were multigene family members and were distributed on different chromosomes. Moreover, two genes (BnGRT2 and BnMYB28) associated with GS content were validated by the qRT-PCR analysis of their expression profiles. The further identification and functionalization of these genes will provide useful insight into the mechanism underlying GS biosynthesis and allocation in B. napus, and the associated SNPs markers could be helpful for molecular maker-assisted breeding for low seed GS in B. napus.
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http://dx.doi.org/10.3390/genes6041215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690036PMC
November 2015