7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome

Tian, Mi; Zeng, Yan; Hu, Yilan; Yuan, Xiangliang; Liu, Shumin; Li, Jie; Lü, Ping; Sun, Yao; Gao, Lei; Fu, Dehao; Li, Yang; Wang, Shasha; McClintock, Shawn M.

doi:10.1016/j.neuropharm.2014.09.006

Cited by 50 publications

(53 citation statements)

References 63 publications

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“…It could also ameliorate spatial memory deficits via increasing synapse protein level of AMPA subunits even in the absence of attenuating expression of amyloid precursor protein or Aβ in the Tg2576 AD mouse model (Gao et al, 2016). Besides AD-associated memory impairment, 7,8-DHF could also reverse memory deficits in schizophrenia (Yang et al, 2014), Fragile x syndrome (Tian et al, 2015), scopolamine-induced memory dysfunction (Chen et al, 2014), and age-related cognitive impairment (Zeng et al, 2012). But whether it could ameliorate cognitive deficits in ApoE-KO mice was still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…As a bioavailable chemical, 7,8-DHF can penetrate brain blood barrier upon intraperitoneal or oral administration to provoke TrkB and its downstream signaling, such as phosphoinositide 3-kinase/protein kinase B (Akt; Wu et al, 2014), to exert its central role in pathologic conditions. As a consequence of activating TrkB, 7,8-DHF inhibits obesity in female mice (Chan et al, 2015), reduces spine morphology abnormalities in fragile X syndrome (Tian et al, 2015), enhances axon regeneration and muscle renovation after peripheral nerves injuries (English et al, 2013), improves motor function and prolongs survival in Huntington’s disease (Jiang et al, 2013). Furthermore, it can reverse synapse loss and prevent memory deficits in Alzheimer’s disease (AD; Zhang et al, 2014a; Gao et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice

Tan

Nie

Zhu

et al. 2016

Front. Aging Neurosci.

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7,8-Dihydroxyflavone (7,8-DHF), a tyrosine kinase B agonist that mimics the neuroprotective properties of brain-derived neurotrophic factor, which can not efficiently deliver into the brain, has been reported to be useful in ameliorating cognitive impairment in many diseases. Researches have indicated that apolipoprotein E-knockout (ApoE-KO) mouse was associated with cognitive alteration via various mechanisms. Our present study investigated the possible mechanisms of cognitive impairment of ApoE-KO mouse fed with western type diet and the protective effects of 7,8-DHF in improving spatial learning and memory in ApoE-KO mouse. Five-weeks-old ApoE-KO mice and C57BL/6 mice were chronically treated with 7,8-DHF (with a dosage of 5 mg/kg) or vehicles orally for 25 weeks, and then subjected to Morris water maze at the age of 30 weeks to evaluate the cognitive performances. Afterward, histology analysis and western blotting were performed. Spatial learning and memory deficits were observed in ApoE-KO mice, which were consistent with higher expression of active-asparaginyl endopeptidase (active-AEP) as well as AEP-derived truncated tau N368 compared with normal group. In addition to that, long-term treatment of 7,8-DHF dramatically ameliorated cognitive decline in ApoE-KO mice, accompanied by the activation in phosphorylated protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway and down-regulated expression of tau S396 and PHF-tau (phosphorylated tau at ser396 and ser404 epitope). These findings suggested that cognitive impairment of ApoE-KO mouse might associate with tau pathology and 7,8-DHF could activate AKT and then phosphorylate its downstream molecule to inhibit expression of abnormal tau, meanwhile, 7,8-DHF could reduce the expression of active-AEP and then inhibit production of truncated tau N368.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice

Tan

Nie

Zhu

et al. 2016

Front. Aging Neurosci.

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“…The stock solution (1 ml) was added to 100 ml of Hydropac water that contained 1% sucrose (pH = 7.4), and subsequently was given to mice as drinking water (1 mg/mL of 7,8-DHF). The dose of 7,8-DHF was selected as previously reported53. The VEH contained the same concentration of sucrose and DMSO.…”

Section: Methodsmentioning

confidence: 99%

Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation

Han

Zhang

Yao

et al. 2016

Sci Rep

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Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus. Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice. These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia.

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“…In another study using mice lacking Fmr1 , dendritic spines aberrantly proliferated in the hippocampus, and 7,8-DHF reduced densities to typical levels (Tian et al, 2015). Together, these findings suggest that 7,8-DHF promotes homeostatic dendritic spine plasticity, rather than simply increasing or decreasing spine numbers.…”

Section: Regulation Of Neuron Structurementioning

confidence: 99%

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

Pitts

Taylor

Gourley

2016

Neurobiology of Disease

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Brain-derived neurotrophic factor (BDNF) affects synaptic plasticity and neural structure and plays key roles in learning and memory processes. Recent evidence also points to important, yet complex, roles for BDNF in rodent models of cocaine abuse and addiction. Here we examine the role of prefrontal cortical (PFC) BDNF in reward-related decision making and behavioral sensitivity to, and responding for, cocaine. We focus on BDNF within the medial and orbital PFC, its regulation by cocaine during early postnatal development and in adulthood, and how BDNF in turn influences responding for drug reinforcement, including in reinstatement models. When relevant, we draw comparisons and contrasts with experiments using natural (food) reinforcers. We also summarize findings supporting, or refuting, the possibility that BDNF in the medial and orbital PFC regulate the development and maintenance of stimulus-response habits. Further investigation could assist in the development of novel treatment approaches for cocaine use disorders.

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7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome

Cited by 50 publications

References 63 publications

7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice

7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice

Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

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