Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise / 神经科学通报·英文版

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

Reprogramming Glial Cells into Functional Neurons for Neuro-regeneration: Challenges and Promise / 神经科学通报·英文版

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

Serotonin induces or inhibits neuritic regeneration of leech CNS neurons depending on neuronal identity

Recovery of motor function after central nervous system (CNS) injury is dependent on the regeneration capacity of the nervous system, which is a multifactorial process influenced, among other things, by the role of neuromodulators such as serotonin. The neurotransmitter serotonin can promote neuronal regeneration but there are also reports of it causing restriction, so it is important to clarify these divergent findings in order to understand the direct scope and side effects of potential pharmacological treatments. We evaluated the effect of serotonin on the extent of neuritic outgrowth and morphology of three different neuronal types in the leech Haementeria officinalis during their regeneration in vitro: Retzius interneurons (Rz), annulus erector (AE) motoneurons, and anterolateral number 1 (AL1) CNS neurons. Neurons were isolated and cultured in L15 medium, with or without serotonin. Growth parameters were registered and quantified, and observed differences were analyzed. The addition of serotonin was found to induce AL1 neurons to increase their average growth dramatically by 8.3-fold (P=0.02; n=5), and to have no clear effect on AE motoneurons (P=0.44; n=5). For Rz interneurons, which normally do not regenerate their neurites, the addition of concanavaline-A causes substantial growth, which serotonin was found to inhibit on average by 98% (P=0.02; n=5). The number of primary neurites and their branches were also affected. These results reveal that depending on the neuronal type, serotonin can promote, inhibit, or have no effect on neuronal regeneration. This suggests that after CNS injury, non-specific pharmacological treatments affecting serotonin may have different effects on different neuronal populations.

Caracterización óptica del Sistema Nervioso Central de Haementeria officinalis / Optical characterization of the Central Nervous System of Haementeria officinalis

Resumen: La falla en la regeneración de las neuronas del sistema nervioso central (SNC) en vertebrados superiores es un problema que no se ha resuelto completamente, esto limita la rehabilitación de muchas conductas motoras después de una lesión en la médula espinal. En la regeneración neuronal intervienen múltiples factores y de estos, los que inducen el crecimiento neurítico se han estudiado para intentar favorecer la extensión y la reconexión de las neuronas lesionadas con sus blancos. La regeneración del SNC de sanguijuelas se ha estudiado intensamente porque permite abordar el problema a diferentes niveles con distintas técnicas, en este trabajo se obtuvo el espectro de absorción óptico, con espectroscopía fotoacústica (EFA), del SNC y de tejido de la sanguijuela Haementeria officinalis, con el objetivo de conocer las longitudes de onda óptimas para la irradiación posterior de células del SNC y de tejido H. officinalis. Los resultados de este estudio muestran que el SNC de estos organismos absorbe en la region comprendida de 300 nm a 500 nm, y las muestras de tejido tienen un máximo de absorción óptico proximo a 300 nm, además se observaron diferencias evidentes entre los espectros de absorción ópticos del SNC con lesión y el control (sin lesión).

Abstract: The failure in the neuron regeneration in the central nervous system (CNS) in higher vertebrates, is a not completely solved problem, this limits the rehabilitation of many motor conducts after an injury in the spinal cord. In neuronal regeneration multiple factors are involved, between them those that induce the neurite outgrowth which has been studied to try to encourage the extension and reconnection of the injury neurons with their blanks. The regeneration of the CNS of leeches has been intensely studied because allows to approach the problem at different levels with different techniques. In this study the optical absorption spectrum of the CNS and the tissue of the leech H. officinalis was obtained, by using photoacoustic spectroscopy (PAS), in order to investigate the optimal wavelenghts for later irradiation of CNS cells and tissue of H. officinalis. The results of this study show that the CNS of these organisms absorbs in the region of 300 nm to 500 nm, and the tissue samples has a maximun of optical absorption near to 300 nm, besides were observed evident differences between the optical absorption spectra of CNS with injury and the control (without injury).

Study of axonal guidance growth cue netrin-1 on nano-materials in nerve regeneration / 中国药理学与毒理学杂志

Nerve regeneration is a major problem in our society after nerve injury.With the development of nanotechnology,some nano-materials,such as carbon nanotubes and graphene with electrical conductivity,have been used to promote neuronfunctional recovery.Some of the nano-materials,however,are neurotoxic and cause neuronal apoptosis.Nerve injury often leads to the disruption of axons,and broken axons cannot form synapse with target neurons,which affects the repair and regeneration of nerves.Netrin-1 is an important cue in neurogenesis,which can guide the growth and migration of axons and synapse formation during neuronal regeneration.However,some growth factors are used to decorate the surface of nanomateriaes to decrease the toxicity in medicine,but the molecular mechanism by which netrin-1 mediates the toxicity of nanomaterials is not clear yet.In this study,we investigated the nano-materials and the function of netrin-1 in neuronal regeneration in recent years.We have proved that netrin-1 can not only guide the growth and migration of axon and synapse formation,but also promote functional recovery of the neurons which are injured by the toxicity of nanomaterials.Our review will provide a theoretical basis for neuronal regeneration by nanomaterials.