The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the...The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord iniury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, caspase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental fndings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.展开更多
Tooth loss has been shown to affect learning and memory in mice and increases the risk of Alz- heimer＇s disease. The dentate gyrus is strongly associated with cognitive function. This study hypothesized that tooth lo...Tooth loss has been shown to affect learning and memory in mice and increases the risk of Alz- heimer＇s disease. The dentate gyrus is strongly associated with cognitive function. This study hypothesized that tooth loss affects neurons in the dentate gyrus. Adult male mice were randomly assigned to either the tooth loss group or normal control group. In the tooth loss group, the left maxillary and mandibular molars were extracted. Normal control mice did not receive any intervention. Immunofluorescence staining revealed that the density and absorbance of double- cortinand neuronal nuclear antigen-positive cells were lower in the tooth loss group than in the normal control group. These data suggest that tooth loss may inhibit neurogenesis in the dentate gyrus of adult mice.展开更多
Disabling hearing loss is the most common sensorineural disability worldwide.It affects around 466 million people and its incidence is expected to rise to around 900 million people by 2050,according to World Health Or...Disabling hearing loss is the most common sensorineural disability worldwide.It affects around 466 million people and its incidence is expected to rise to around 900 million people by 2050,according to World Health Organization estimates.Most cases of hearing impairment are due to the degeneration of hair cells(HCs)in the cochlea,mechano-receptors that transduce incoming sound information into electrical signals that are sent to the brain.Damage to these cells is mainly caused by exposure to aminoglycoside antibiotics and to some anti-cancer drugs such as cisplatin,loud sounds,age,infections and genetic mutations.Hearing deficits may also result from damage to the spiral ganglion neurons that innervate cochlear HCs.Differently from what is observed in avian and nonmammalian species,there is no regeneration of missing sensory cell types in the adult mammalian cochlea,what makes hearing loss an irreversible process.This review summarizes the research that has been conducted with the aim of developing cell-based strategies that lead to sensory cell replacement in the adult cochlea and,ultimately,to hearing restoration.Two main lines of research are discussed,one directed toward the transplantation of exogenous replacement cells into the damaged tissue,and another that aims at reactivating the regenerative potential of putative progenitor cells in the adult inner ear.Results from some of the studies that have been conducted are presented and the advantages and drawbacks of the various approaches discussed.展开更多
Hidden hearing loss(HHL),an auditory dysfunction that has gained much recent attention,has the hallmarks of speech discrimination and intelligibility deficits with normal or near-normal hearing thresholds.The patholog...Hidden hearing loss(HHL),an auditory dysfunction that has gained much recent attention,has the hallmarks of speech discrimination and intelligibility deficits with normal or near-normal hearing thresholds.The pathological mechanisms of HHL are complicated and are not yet fully understood.HHL can be resulted from disorders of the central nervous system such as auditory cortex,and/or pathological changes of inner ear.Thus far,2 pathological phenomena,synaptopathy and auditory nerve demyelination,have been reported as underlying causes of otogenic HHL.Here,we review the clinical and physiological characteristics of HHL as well as the molecular pathological mechanisms of otogenic HHL and aim to allude to potential therapy targets for clinical applications in the future.展开更多
This study examined the expression pattern of programmed cell death 5 (PDCD5) in co-chlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) m...This study examined the expression pattern of programmed cell death 5 (PDCD5) in co-chlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.展开更多
Auditory neuropathy is the particular form of deafness in humans which cannot be treated by replacement therapy.Human dental pulp stem cells(hDPSCs)are derived from an ectomesenchymal neural crest cell population.Ther...Auditory neuropathy is the particular form of deafness in humans which cannot be treated by replacement therapy.Human dental pulp stem cells(hDPSCs)are derived from an ectomesenchymal neural crest cell population.Therefore,they possess a promising capacity for neuronal differentiation and repair.miR-124,a key regulator of neuronal development in the inner ear,is expressed at high levels in auditory and vestibular neurons.Here,we evaluated the possible effect of miR-124 in alteration of neural protein markers expression.Using quantitative reverse transcription-PCR(qRT-PCR)analyses and immunofluorescence staining,we studied the expression patterns of neural progenitor markers(Nestin,NOTCH1,and SOX2)and neural markers(b-tubulin Ⅲ,GATA-3,and peripherin)upon transfection of hDPSCs with miR-124.The qRT-PCR results showed that Nestin was upregulated 6 h post-transfection.In contrast,Nestin expression exhibited a decreasing trend 24 h and 48 h post-transfection.Higher levels of b-tubulin Ⅲ,6 h and 16 h post transfection in RNA level as compared with control cells,were determined in transfected DPSCs.However,b-tubulin-Ⅲ expression decreased 48 h post-transfection.The immunoflourescence results indicated that transfection of hDPSCs with miR-124,only affected Nestin among the studied neural progenitor and neural marker expression in protein level.展开更多
基金supported by grants from the National Natural Science Foundation of China,No.81171799,81471854a Special Financial Grant from the China Postdoctoral Science Foundation,No.2013T60948
文摘The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord iniury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, caspase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental fndings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.
基金supported by the Science and Technology Key Project of Ministry of Education of China,No.106152the Scientific Research Project of Second Hospital of Lanzhou University of China,No.C1708
文摘Tooth loss has been shown to affect learning and memory in mice and increases the risk of Alz- heimer＇s disease. The dentate gyrus is strongly associated with cognitive function. This study hypothesized that tooth loss affects neurons in the dentate gyrus. Adult male mice were randomly assigned to either the tooth loss group or normal control group. In the tooth loss group, the left maxillary and mandibular molars were extracted. Normal control mice did not receive any intervention. Immunofluorescence staining revealed that the density and absorbance of double- cortinand neuronal nuclear antigen-positive cells were lower in the tooth loss group than in the normal control group. These data suggest that tooth loss may inhibit neurogenesis in the dentate gyrus of adult mice.
文摘Disabling hearing loss is the most common sensorineural disability worldwide.It affects around 466 million people and its incidence is expected to rise to around 900 million people by 2050,according to World Health Organization estimates.Most cases of hearing impairment are due to the degeneration of hair cells(HCs)in the cochlea,mechano-receptors that transduce incoming sound information into electrical signals that are sent to the brain.Damage to these cells is mainly caused by exposure to aminoglycoside antibiotics and to some anti-cancer drugs such as cisplatin,loud sounds,age,infections and genetic mutations.Hearing deficits may also result from damage to the spiral ganglion neurons that innervate cochlear HCs.Differently from what is observed in avian and nonmammalian species,there is no regeneration of missing sensory cell types in the adult mammalian cochlea,what makes hearing loss an irreversible process.This review summarizes the research that has been conducted with the aim of developing cell-based strategies that lead to sensory cell replacement in the adult cochlea and,ultimately,to hearing restoration.Two main lines of research are discussed,one directed toward the transplantation of exogenous replacement cells into the damaged tissue,and another that aims at reactivating the regenerative potential of putative progenitor cells in the adult inner ear.Results from some of the studies that have been conducted are presented and the advantages and drawbacks of the various approaches discussed.
基金the National Natural Science Foundation of China(No.81771010,81570911)the Nature Science Foundation(No.17ZR1404600)from Shanghai Science and Technology Committee,China.
文摘Hidden hearing loss(HHL),an auditory dysfunction that has gained much recent attention,has the hallmarks of speech discrimination and intelligibility deficits with normal or near-normal hearing thresholds.The pathological mechanisms of HHL are complicated and are not yet fully understood.HHL can be resulted from disorders of the central nervous system such as auditory cortex,and/or pathological changes of inner ear.Thus far,2 pathological phenomena,synaptopathy and auditory nerve demyelination,have been reported as underlying causes of otogenic HHL.Here,we review the clinical and physiological characteristics of HHL as well as the molecular pathological mechanisms of otogenic HHL and aim to allude to potential therapy targets for clinical applications in the future.
基金supported by a grant from the National Natural Science Foundation of China (No. 30672307)
文摘This study examined the expression pattern of programmed cell death 5 (PDCD5) in co-chlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.
基金supported by deputy of research and technology of Shahrekord University of Medical Sciences(grant number 2178)
文摘Auditory neuropathy is the particular form of deafness in humans which cannot be treated by replacement therapy.Human dental pulp stem cells(hDPSCs)are derived from an ectomesenchymal neural crest cell population.Therefore,they possess a promising capacity for neuronal differentiation and repair.miR-124,a key regulator of neuronal development in the inner ear,is expressed at high levels in auditory and vestibular neurons.Here,we evaluated the possible effect of miR-124 in alteration of neural protein markers expression.Using quantitative reverse transcription-PCR(qRT-PCR)analyses and immunofluorescence staining,we studied the expression patterns of neural progenitor markers(Nestin,NOTCH1,and SOX2)and neural markers(b-tubulin Ⅲ,GATA-3,and peripherin)upon transfection of hDPSCs with miR-124.The qRT-PCR results showed that Nestin was upregulated 6 h post-transfection.In contrast,Nestin expression exhibited a decreasing trend 24 h and 48 h post-transfection.Higher levels of b-tubulin Ⅲ,6 h and 16 h post transfection in RNA level as compared with control cells,were determined in transfected DPSCs.However,b-tubulin-Ⅲ expression decreased 48 h post-transfection.The immunoflourescence results indicated that transfection of hDPSCs with miR-124,only affected Nestin among the studied neural progenitor and neural marker expression in protein level.
