Restorative neurology and neuroscience · 2018
snRPN controls the ability of neurons to regenerate axons.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Mertsch Sonja, Schlicht Katrin, Melkonyan Harutyun, Schlatt Stefan, Thanos Solon
Аннотация
BACKGROUND: Retinal ganglion cells (RGCs) of mammals lose the ability to regenerate injured axons during postnatal maturation, but little is known about the underlying molecular mechanisms.
OBJECTIVE: It remains of particular importance to understand the mechanisms of axonal regeneration to develop new therapeutic approaches for nerve injuries.
METHODS: Retinas from newborn to adult monkeys (Callithrix jacchus)1 were obtained immediately after death and cultured in vitro. Growths of axons were monitored using microscopy and time-lapse video cinematography. Immunohistochemistry, Western blotting, qRT-PCR, and genomics were performed to characterize molecules associated with axonal regeneration and growth. A genomic screen was performed by using retinal explants versus native and non-regenerative explants obtained from eye cadavers on the day of birth, and hybridizing the mRNA with cross-reacting cDNA on conventional human microarrays. Followed the genomic screen, siRNA experiments were conducted to identify the functional involvement of identified candidates.
RESULTS: Neuron-specific human ribonucleoprotein N (snRPN) was found to be a potential regulator of impaired axonal regeneration during neuronal maturation in these animals. In particular, up-regulation of snRPN was observed during retinal maturation, coinciding with a decline in regenerative ability. Axon regeneration was reactivated in snRPN-knockout retinal ex vivo explants of adult monkey.
CONCLUSION: These results suggest that coordinated snRPN-driven activities within the neuron-specific ribonucleoprotein complex regulate the regenerative ability of RGCs in primates, thereby highlighting a potential new role for snRPN within neurons and the possibility of novel postinjury therapies.
OBJECTIVE: It remains of particular importance to understand the mechanisms of axonal regeneration to develop new therapeutic approaches for nerve injuries.
METHODS: Retinas from newborn to adult monkeys (Callithrix jacchus)1 were obtained immediately after death and cultured in vitro. Growths of axons were monitored using microscopy and time-lapse video cinematography. Immunohistochemistry, Western blotting, qRT-PCR, and genomics were performed to characterize molecules associated with axonal regeneration and growth. A genomic screen was performed by using retinal explants versus native and non-regenerative explants obtained from eye cadavers on the day of birth, and hybridizing the mRNA with cross-reacting cDNA on conventional human microarrays. Followed the genomic screen, siRNA experiments were conducted to identify the functional involvement of identified candidates.
RESULTS: Neuron-specific human ribonucleoprotein N (snRPN) was found to be a potential regulator of impaired axonal regeneration during neuronal maturation in these animals. In particular, up-regulation of snRPN was observed during retinal maturation, coinciding with a decline in regenerative ability. Axon regeneration was reactivated in snRPN-knockout retinal ex vivo explants of adult monkey.
CONCLUSION: These results suggest that coordinated snRPN-driven activities within the neuron-specific ribonucleoprotein complex regulate the regenerative ability of RGCs in primates, thereby highlighting a potential new role for snRPN within neurons and the possibility of novel postinjury therapies.