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Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro

Neural Regeneration Research 2020年第9期15卷 1732-1739页

作者： Michele Fornaro Alessia Giovannelli Angelica Foggetti Luisa Muratori Stefano Geuna Giorgia Novajra Isabelle Perroteau Department of Anatomy College of Graduates Studies(CGS)Chicago College of Osteopathic Medicine(CCOM)Midwestern UniversityDowners GroveILUSA Department of Clinical and Biological Sciences University of TurinTorinoItaly Institute of Physiology Christian-Albrechts-University KielKielGermany Neuroscience Institute Cavalieri Ottolenghi(NICO) TorinoItaly Department of Applied Science and Technology Politecnico di TorinoTorinoItaly

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.

关键词： brain-derived neurotrophic factor directionality dorsal root ganglia explant nerve growth factor nerve regeneration neurite growth enhancement neurotrophic factors neurotrophin-3 sensory neurons tortuosity

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sensory neurons in the spinal cord of nominal female embryos in the marine turtle Lepidochelys olivacea respond to shifts in incubation temperature:implications for temperature dependent sex determination

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Advances in Bioscience and Biotechnology 2011年第1期2卷 1-7页

作者： Francisco Jimenez-Trejo Leonora Olivos-Cisneros Julieta Mendoza-Torreblanca Sofia Diaz-Cintra Esperanza-Melendez-Herrera Armida Baez-Saldana Patricia Padilla Cortes Gabriel Gutierrez-Ospina Alma Lilia Fuentes-Farias Departamento de Biologia Facultad de QuimicaUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510 Departamento de Biologia Celular y Fisiologia Instituto de Investigaciones BiomedicasUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510 Departamento de Neuroquimica Instituto Nacional de PediatriaMexicoDF.Mexico 04530 Departamento de Neurobiologia del Desarrollo y Neurofisiologia Instituto de NeurobiologiaUniversidad Nacional Autonoma de MexicoCampus UNAM-JuriquillaJuriquillaQueretaro Mexico AP.1-1141 Laboratorio de Invertebrados y Ecofisiologia Animal Facultad de BiologiaUniversidad Michoacana de San Nicolas de HidalgoMoreliaMichoacanMexico 58040 Unidad de Cromatografia Liquida de Alta Resolucion Instituto de Investigaciones BiomedicasUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510

Gonadal determination in marine turtles depends on incubation temperature. The mechanisms that spark off this process remain unclear. Previously, we proposed that sensory nerves reaching the gonadal primordium in nominal female embryos of Lepidochelys (L) olivacea may sense and signal incubation temperature. These nerves could later trigger ovarian determination by releasing neurotransmitters in a code constructed based on the thermal information (Gutierrez-Ospina et al., Acetylcholinesterase-positive innervation is present at the undifferentiated stages of the sea turtle Lepidochelys olivacea embryo gonads: implications for temperature-dependent sex determination, J. Comp. Neurol. 410 (1999) 90-98). The hypothesis briefly described, however, has been recently refuted under weak theoretical grounds and experimental misinterpretations (see introduction). Here, we present preliminary results that show that nominal female embryos have sensory neurons located in the dorsal horn laminae I and II of the lumbar spinal cord that display increased c-Fos-like immuno-staining after being incubated either at 15°C or 50°C. Because these spinal neurons are the primary central target of dorsal root ganglion neurons that innervate the urogential crest, these observations keep open the possibility that gonadal sensory nerves indeed signal thermal information that could later be used to trigger or instruct ovarian specification in marine turtles.

关键词： Reptiles Ovarian Determination c-Fos Incubation Temperature sensory neurons

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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner Department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA Department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Alexa Fluor 488-conjugated cholera toxin subunit B optimally labels neurons 3-7 days after injection into the rat gastrocnemius muscle

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Neural Regeneration Research 2022年第10期17卷 2316-2320页

作者： Jing-Jing Cui Jia Wang Dong-Sheng Xu Shuang Wu Ya-Ting Guo Yu-Xin Su Yi-Han Liu Yu-Qing Wang Xiang-Hong Jing Wan-Zhu Bai Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijingChina

Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve ***,it is not always clear which tracer should be used to yield optimal *** this study,we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B(AF488-CTB).This was injected into the gastrocnemius muscle of rats,and it was found that motor,sensory,and sympathetic neurons were labeled in the spinal ventral horn,dorsal root ganglia,and sympathetic chain,*** results were obtained when we injected AF594-CTB into the tibialis anterior *** morphology and number of neurons were evaluated at different time points following the AF488-CTB *** was found that labeled motor and sensory neurons could be observed 12 hours *** intensity was found to increase over time,and the morphology appeared clear and complete 3-7 days post-injection,with clearly distinguishable motor neuron axons and ***,14 days after the injection,the quality of the images decreased and the neurons appeared blurred and *** and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features,and the surrounding microglia were also found to be ***,these results imply that the cholera toxin subunit B,whether unconjugated or conjugated with Alexa Fluor,is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.

关键词： Alexa Fluor-conjugated cholera toxin subunit B calcitonin gene-related peptide microglia motor neurons neural tract tracing optimal time window sensory neurons somatotopic organization sympathetic neurons tibialis anterior muscle

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The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen Martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain Departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general *** reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in *** the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical ***,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative ***,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic *** importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

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The balance between efficient anti-inflammatory treatment and neuronal regeneration in the olfactory epithelium

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Neural Regeneration Research 2018年第10期13卷 1711-1714页

作者： Seo Young Chang Isaias Glezer Department of Biochemistry Escola Paulista de MedicinaUniversidade Federal de SAo Paulo

The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（OE）. Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.

关键词： anti-inflammatory drugs corticosteroids hyposmia inflammation rhinosinusitis olfactory epithelium sensory neurons cell proliferation

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Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia

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Neural Regeneration Research 2015年第11期10卷 1865-1868页

作者： Xu-yang Wang Pei-yuan Gu Shi-wen Chen Wen-wei Gao Heng-li Tian Xiang-he Lu Wei-ming Zheng Qi-chuan Zhuge Wei-xing Hu Department of Neurosurgery First Affiliated Hospital of Nanjing Medical University Department of Neurosurgery Shanghai Jiao Tong University Affiliated 6th People’s Hospital Department of Neurosurgery First Affiliated Hospital of Wenzhou Medical University

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

关键词： nerve regeneration neurotrophin-3 sensory neurons dorsal root ganglion cats nerveterminal neural regeneration

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Progesterone and peripheral nerve regeneration

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Neural Regeneration Research 2006年第2期1卷 173-176页

作者： Fei Fan Haichao Li Yuwei Wang Yanglin Zheng Lianjun Jia Zhihui Wang Department of Orthopaedics Third Hospital of Datong CityDatong 037008. ShanxiProvince China

OBJECTIVE： To explore the effect of progesterone on peripheral nerve regeneration DATA SOURCES： An online search of Medline and OVID databases was under taken to identify articles about progesterone and peripheral nerve regeneration published in English between January 1990 and June 2004 by using the keywords of ＂peripheral nerve, injury, progesterone, regeneration＂. STUDY SELECTION： The data were primarily screened, those correlated with progesterone and peripheral nerve regeneration were involved, and their original articles were further searched, the repetitive studies or reviews were excluded. DATA EXTRACTION ： Totally 59 articles about progesterone and peripheral nerve regeneration were collected, and 26 of them were involved, the other 33 excluded ones were the repetitive studies or reviews. DATA SYNTHESIS： Recent researches found that certain amount of progesterone could be synthetized in peripheral nervous system, and the expression of progesterone receptor could be found in sensory neurons and Schwann cells. After combined with the receptor erate the formation of peripheral nerve myelin sheath endogenous and exogenous progesterone can accelalso promote the axonal regeneration. CONCLUSION： Progesterone plays a role in protecting neurons, increasing the sensitivity of nerve tissue to nerve growth factor, and accelerating regeneration of nerve in peripheral nerve regeneration, which provides theoretical references for the treatment of demyelinated disease and nerve injury, as well as the prevention of neuroma, especially that the in vivo level of progesterone should be considered for the elderly people accompanied by neuropathy and patients with congenital luteal phase defect, which is of positive significance in guiding the treatment.

关键词： peripheral nerve regeneration progesterone receptor nerve growth factor axonal regeneration sensory neurons nervous system elderly people Schwann cells prevention of myelin sheath nerve tissue nerve injury

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