Neural Regeneration Research

The hypothalamic-spinal dopaminergic system: a target for pain modulation Michelino Puopolo Neural Regeneration Research 2019 14(6):925-930 Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise, among others, noradrenergic, serotonergic, γ-aminobutyric acid (GABA)ergic, and dopaminergic fibers. The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood. The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases Yuan Qu, Yi Liu, Ahmed Fayyaz Noor, Johnathan Tran, Rui Li Neural Regeneration Research 2019 14(6):931-938 Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Gene expression changes in dorsal root ganglia following peripheral nerve injury: roles in inflammation, cell death and nociception Sarah L Martin, Adam J Reid, Alexei Verkhratsky, Valerio Magnaghi, Alessandro Faroni Neural Regeneration Research 2019 14(6):939-947 Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.

Nicotinamide adenine dinucleotide phosphate oxidase activation and neuronal death after ischemic stroke Jiamei Shen, Radhika Rastogi, Xiaokun Geng, Yuchuan Ding Neural Regeneration Research 2019 14(6):948-953 Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however, excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research, coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.

Autophagy: novel insights into therapeutic target of electroacupuncture against cerebral ischemia/ reperfusion injury Ya-Guang Huang, Wei Tao, Song-Bai Yang, Jin-Feng Wang, Zhi-Gang Mei, Zhi-Tao Feng Neural Regeneration Research 2019 14(6):954-961 Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway. This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.

Lessons from glaucoma: rethinking the fluid-brain barriers in common neurodegenerative disorders Francisco Javier Carreras Neural Regeneration Research 2019 14(6):962-966 Glaucoma has been recently characterized as a member of the group of anoikis-related diseases. Anoikis, a form of apoptosis, can be triggered by the unfastening of adherent junctions present in astrocytes. In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes, a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves. In glaucoma, the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head. The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes. As the cerebrospinal fluid has a similar base calcium concentration, a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons. Here the similitude between glaucoma, amyotrophic lateral sclerosis and Alzheimer’s disease are discussed and the concept of the break in the fluid-brain barrier, as an event separated from the blood-brain barrier, is stressed.

Busting the myth: more good than harm in transgenic cells Gonzalo Piñero, Patricia Setton-Avruj Neural Regeneration Research 2019 14(6):967-968

Muscle secretion of toxic factors, regulated by miR126-5p, facilitates motor neuron degeneration in amyotrophic lateral sclerosis Roy Maimon, Eran Perlson Neural Regeneration Research 2019 14(6):969-970

Preliminary in vitro evaluation of neuroprotective and monoamine oxidase type B inhibitory effects of newly synthesized 8-aminocaffeines Magdalena Kondeva-Burdina, Maya Georgieva, Alexandra Kasabova-Angelova, Virginia Tzankova, Alexander Zlatkov Neural Regeneration Research 2019 14(6):971-972

Therapeutic exploitation of the S-nitrosoglutathione/S-nitrosylation mechanism for the treatment of contusion spinal cord injury Mushfiquddin Khan, Inderjit Singh Neural Regeneration Research 2019 14(6):973-974