Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotro...Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.展开更多
Spinal muscular atrophy(SMA)is a hereditary pediatric motor neuron(MN)disease:survival motor neuron 1(SMN1)gene mutation determines MN degeneration and,consequently,muscle atrophy,breathing and swallowing diffi...Spinal muscular atrophy(SMA)is a hereditary pediatric motor neuron(MN)disease:survival motor neuron 1(SMN1)gene mutation determines MN degeneration and,consequently,muscle atrophy,breathing and swallowing difficulties,and,in the most severe cases,premature death.A second unaffected gene(SMN2)is present,but it can only produce a limited amount of functional protein,modulating the disease severity and progression.展开更多
Brain plasticity is heterogeneous in mammals:Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and oth...Brain plasticity is heterogeneous in mammals:Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system(CNS)do represent a heavy health and social burden.Efficacious re-generative processes are not" a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced (if compared to those occurring in non-mammalian vertebrates) and hardly inducible by therapeutic approaches (reviewed in Martino et al., 2011).展开更多
Schwann cells(SCs)and peripheral nerve regeneration:SCs are the principal glial cells of the peripheral nervous system(PNS).In a healthy nerve,myelinating SCs wrap around larger caliber motor and sensory axons to...Schwann cells(SCs)and peripheral nerve regeneration:SCs are the principal glial cells of the peripheral nervous system(PNS).In a healthy nerve,myelinating SCs wrap around larger caliber motor and sensory axons to form the myelin sheath,whereas non-myelinating SCs envelop and support multiple small diameter sensory axons to form Remak bundles.Moreover,they form a basal lamina which surround each SC-axon unit(Hall,2005).When a peripheral nerve injury occurs,展开更多
Peripheral nerves form a complex network connecting the central nervous system and the body. Injuries to peripheral nerves often lead to partial or complete loss of motor, sen- sory and autonomic functions, thus inter...Peripheral nerves form a complex network connecting the central nervous system and the body. Injuries to peripheral nerves often lead to partial or complete loss of motor, sen- sory and autonomic functions, thus interfering with many aspects of an individual's life.展开更多
Brain regeneration from an evolutionary perspective:Brain regeneration(the full restoration of tissue after loss from injury or disease)is the most sought after goal for researchers working in developmental neurobiolo...Brain regeneration from an evolutionary perspective:Brain regeneration(the full restoration of tissue after loss from injury or disease)is the most sought after goal for researchers working in developmental neurobiology.It also appears to be the most challenging to achieve when considering the mammalian brain.Whereas remarkable regenerative capacities can be present in the central nervous systems of many non-mammalian vertebrates(e.g.,fish,amphibians),these kinds of processes appear to be dramatically reduced in mammals(Bonfanti,2011).展开更多
基金supported by the research start-up and the MWU’s intramural grant(to MF)the Italian MURST-MIUR foundation(to SG and IP)
文摘Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.
文摘Spinal muscular atrophy(SMA)is a hereditary pediatric motor neuron(MN)disease:survival motor neuron 1(SMN1)gene mutation determines MN degeneration and,consequently,muscle atrophy,breathing and swallowing difficulties,and,in the most severe cases,premature death.A second unaffected gene(SMN2)is present,but it can only produce a limited amount of functional protein,modulating the disease severity and progression.
基金supported by MIUR-PRIN2015(grant 2015Y5W9YP)University of Turin(Ricerca locale 2016)
文摘Brain plasticity is heterogeneous in mammals:Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system(CNS)do represent a heavy health and social burden.Efficacious re-generative processes are not" a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced (if compared to those occurring in non-mammalian vertebrates) and hardly inducible by therapeutic approaches (reviewed in Martino et al., 2011).
文摘Schwann cells(SCs)and peripheral nerve regeneration:SCs are the principal glial cells of the peripheral nervous system(PNS).In a healthy nerve,myelinating SCs wrap around larger caliber motor and sensory axons to form the myelin sheath,whereas non-myelinating SCs envelop and support multiple small diameter sensory axons to form Remak bundles.Moreover,they form a basal lamina which surround each SC-axon unit(Hall,2005).When a peripheral nerve injury occurs,
基金funding from the European Community’s Seventh Framework Program(FP7-HEALTH-2011)under grant agreement,No.278612(BIOHYBRID)
文摘Peripheral nerves form a complex network connecting the central nervous system and the body. Injuries to peripheral nerves often lead to partial or complete loss of motor, sen- sory and autonomic functions, thus interfering with many aspects of an individual's life.
文摘Brain regeneration from an evolutionary perspective:Brain regeneration(the full restoration of tissue after loss from injury or disease)is the most sought after goal for researchers working in developmental neurobiology.It also appears to be the most challenging to achieve when considering the mammalian brain.Whereas remarkable regenerative capacities can be present in the central nervous systems of many non-mammalian vertebrates(e.g.,fish,amphibians),these kinds of processes appear to be dramatically reduced in mammals(Bonfanti,2011).