Thioredoxin and glutaredoxin system proteins—immunolocalization in the rat central nervous system

Background

The oxidoreductases of the thioredoxin (Trx) family of proteins play a major role in the cellular response to oxidative stress. Redox imbalance is a major feature of brain damage. For instance, neuronal damage and glial reaction induced by a hypoxic–ischemic episode is highly related to glutamate excitotoxicity, oxidative stress and mitochondrial dysfunction. Most animal models of hypoxia–ischemia in the central nervous system (CNS) use rats to study the mechanisms involved in neuronal cell death, however, no comprehensive study on the localization of the redox proteins in the rat CNS was available.

Methods

The aim of this work was to study the distribution of the following proteins of the thioredoxin and glutathione/glutaredoxin (Grx) systems in the rat CNS by immunohistochemistry: Trx1, Trx2, TrxR1, TrxR2, Txnip, Grx1, Grx2, Grx3, Grx5, and γ-GCS, peroxiredoxin 1 (Prx1), Prx2, Prx3, Prx4, Prx5, and Prx6. We have focused on areas most sensitive to a hypoxia–ischemic insult: Cerebellum, striatum, hippocampus, spinal cord, substantia nigra, cortex and retina.

Results and conclusions

Previous studies implied that these redox proteins may be distributed in most cell types and regions of the CNS. Here, we have observed several remarkable differences in both abundance and regional distribution that point to a complex interplay and crosstalk between the proteins of this family.

General significance

We think that these data might be helpful to reveal new insights into the role of thiol redox pathways in the pathogenesis of hypoxia–ischemia insults and other disorders of the CNS.This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases.     

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

Objective

To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain.

Methods

Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot.

Results

Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.).

Conclusion

ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.     

Spinal mechanism of micturition reflex inhibition by naftopidil in rats

Aim

We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats.

Methods

The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions.

Key findings

Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1 mg) or IT (0.1 μg) noradrenaline evoked bladder contractions, but IV (1 mg) or IT (0.01–1 μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions.

Significance

Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system.     

Abnormal glycogen in astrocytes is sufficient to cause adult polyglucosan body disease

Background

A 45-year old woman of Cambodian ethnic background presented with fatal respiratory failure due to a severe diaphragmatic dysfunction. Two years before, she had developed early onset of urinary symptoms.

Methods and results

Neuroimaging showed atrophy of the spine and medulla as well as a leukodystrophy affecting both supra- and infra-tentorial regions. At autopsy, polyglucosan bodies (PB) were seen in several peripheral tissues, including the diaphragm, and nervous tissues such as peripheral nerves, cerebral white matter, basal ganglia, hippocampus, brainstem and cerebellum. Immunohistochemistry and electron microscopy of the brain revealed an exclusive astrocytic localization of the PB. The diagnosis of adult polyglucosan body disease (APBD) was confirmed by enzymatic and molecular studies.

Conclusion

Storage of abnormal glycogen in astrocytes is sufficient to cause the leukodystrophy of APBD. Since brain glycogen is almost exclusively metabolized in astrocytes, this observation sheds light on the pathophysiology of APBD. In addition, this is the first report of an APBD patient presenting with a subacute diaphragmatic failure.     

Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury

Background

The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous diseases. As BDNF is anterogradely transported by axons, we propose that peripherally derived and/or applied BDNF may act on the regeneration of central axons of ascending sensory neurons.

Methodology/Principal Findings

The present study aimed to test the hypothesis by using conditioning lesion of the sciatic nerve as a model to increase the expression of endogenous BDNF in sensory neurons and by injecting exogenous BDNF into the peripheral nerve or tissues. Here we showed that most of regenerating sensory neurons expressed BDNF and p-CREB but not p75NTR. Conditioning-lesion induced regeneration of ascending sensory neuron and the increase in the number of p-Erk positive and GAP-43 positive neurons was blocked by the injection of the BDNF antiserum in the periphery. Enhanced neurite outgrowth of dorsal root ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the neutralization with the BDNF antiserum. The delivery of exogenous BDNF into the sciatic nerve or the footpad significantly increased the number of regenerating DRG neurons and regenerating sensory axons in the injured spinal cord. In a contusion injury model, an injection of BDNF into the footpad promoted recovery of motor functions.

Conclusions/Significance

Our data suggest that endogenous BDNF in DRG and spinal cord is required for the enhanced regeneration of ascending sensory neurons after conditioning lesion of sciatic nerve and peripherally applied BDNF may have therapeutic effects on the spinal cord injury.     

Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study

Aims

The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice.

Main methods

Carvacrol treatment (12.5–50 mg/kg s.c.) once daily for 15 days was started 24 h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABA_A receptors.

Key findings

CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABA_A.

Significance

Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.     

Neurobiology of exercise

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.     

Aquaporin and brain diseases

Background

The presence of water channel proteins, aquaporins (AQPs), in the brain led to intense research in understanding the underlying roles of each of them under normal conditions and pathological conditions.

Scope of review

In this review, we summarize some of the recent knowledge on the 3 main AQPs (AQP1, AQP4 and AQP9), with a special focus on AQP4, the most abundant AQP in the central nervous system.

Major conclusions

AQP4 was most studied in several brain pathological conditions ranging from acute brain injuries (stroke, traumatic brain injury) to the chronic brain disease with autoimmune neurodegenerative diseases. To date, no specific therapeutic agents have been developed to either inhibit or enhance water flux through these channels. However, experimental results strongly underline the importance of this topic for future investigation. Early inhibition of water channels may have positive effects in prevention of edema formation in brain injuries but at later time points during the course of a disease, AQP is critical for clearance of water from the brain into blood vessels.

General significance

Thus, AQPs, and in particular AQP4, have important roles both in the formation and resolution of edema after brain injury. The dual, complex function of these water channel proteins makes them an excellent therapeutic target. This article is part of a Special Issue entitled Aquaporins.     

The acute antinociceptive effect of hyperbaric oxygen is not accompanied by an increase in markers of oxidative stress

Aims

Exposure to hyperbaric oxygen (HBO₂) causes an antinociceptive response in mice. However, breathing oxygen (O₂) at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO₂ antinociception and the toxicity profile of HBO₂.

Main methods

Male NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O₂ at 1.0 or 3.5 atmospheres absolute (ATA), using the acetic acid-induced abdominal constriction test. For the oxygen toxicity test, mice were exposed to 3.5 ATA oxygen for 11 min, 60 min, and 60 min daily for 2 days (120 min) or 60 min daily for 4 days (240 min), then assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl in brain, spinal cord and lung.

Key findings

Only the combination of 100% O₂ and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O₂ was pressure-dependent up to 3.5 ATA. In the oxygen toxicity test, mice exposed to HBO₂ for different time intervals had levels of brain, spinal cord and lung MDA and protein carbonyl that were comparable to that of control animals exposed to room air.

Significance

Treatment with 100% O₂ evokes a pressure-dependent antinociceptive effect. Since there was no significant increase in levels of the oxidative stress markers in the tested tissues, it is concluded that HBO₂ at 3.5 ATA produces antinociception in the absence of oxidative stress in mice.     

Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin-10 and glial inhibitors

Background

Understanding the underlying mechanisms of neuropathic pain caused by damage to the peripheral nervous system remains challenging and could lead to significantly improved therapies. Disturbance of homeostasis not only occurs at the site of injury but also extends to the spinal cord and brain involving various types of cells. Emerging data implicate neuroimmune interaction in the initiation and maintenance of chronic pain hypersensitivity.

Results

In this study, we sought to investigate the effects of TGF-β1, a potent anti-inflammatory cytokine, in alleviating nerve injury-induced neuropathic pain in rats. By using a well established neuropathic pain animal model (partial ligation of the sciatic nerve), we demonstrated that intrathecal infusion of recombinant TGF-β1 significantly attenuated nerve injury-induced neuropathic pain. TGF-β1 treatment not only prevents development of neuropathic pain following nerve injury, but also reverses previously established neuropathic pain conditions. The biological outcomes of TGF-β1 in this context are attributed to its pleiotropic effects. It inhibits peripheral nerve injury-induced spinal microgliosis, spinal microglial and astrocytic activation, and exhibits a powerful neuroprotective effect by preventing the induction of ATF3⁺ neurons following nerve ligation, consequently reducing the expression of chemokine MCP-1 in damaged neurons. TGF-β1 treatment also suppresses nerve injury-induced inflammatory response in the spinal cord, as revealed by a reduction in cytokine expression.

Conclusion

Our findings revealed that TGF-β1 is effective in the treatment of neuropathic by targeting both neurons and glial cells. We suggest that therapeutic agents such as TGF-β1 having multipotent effects on different types of cells could work in synergy to regain homeostasis in local spinal cord microenvironments, therefore contributing to attenuate neuropathic pain.     

综述与专论: 脊髓星形细胞瘤研究进展

脊髓星形细胞瘤是一种罕见的中枢神经系统恶性肿瘤,在流行病学、肿瘤临床学表型、分子遗传标记、治疗及研究方面有着独特特征。虽然随着手术技术的进步以及分子病理的发展,脑胶质瘤的研究和治疗取得较大进展,但脊髓星形细胞瘤的研究和治疗却发展缓慢。其原因一方面在于临床样本较少,难以开展研究,另一方面因其分子遗传独特性,对脑胶质瘤一线化疗药替莫唑胺敏感性差。因而亟需理清脊髓星形细胞瘤的研究现状,为改善其临床疗效梳理潜在方向。基于此,本文综述脊髓星形细胞瘤的临床特征、病理分型、分子遗传特征和当前治疗方法等方面的研究进展,在描绘脊髓星形细胞瘤的临床治疗现状和研究进展的基础上,提出了未来研究和治疗潜在方向。     

Centrally Administered Pertussis Toxin Inhibits Microglia Migration to the Spinal Cord and Prevents Dissemination of Disease in an EAE Mouse Model

Background

Experimental autoimmune encephalomyelitis (EAE) models are important vehicles for studying the effect of infectious elements such as Pertussis toxin (PTx) on disease processes related to acute demyelinating encephalomyelitis (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects on the immune system. This study was designed to investigate the effects of PTx administered intracerebroventricularly (icv) in preventing downstream immune cell infiltration and demyelination of the spinal cord.

Methods and Findings

EAE was induced in C57BL/6 mice with MOG_35–55. PTx icv at seven days post MOG immunization resulted in mitigation of clinical motor symptoms, minimal T cell infiltration, and the marked absence of axonal loss and demyelination of the spinal cord. Integrity of the blood brain barrier was compromised in the brain whereas spinal cord BBB integrity remained intact. PTx icv markedly increased microglia numbers in the brain preventing their migration to the spinal cord. An in vitro transwell study demonstrated that PTx inhibited migration of microglia.

Conclusion

Centrally administered PTx abrogated migration of microglia in EAE mice, limiting the inflammatory cytokine milieu to the brain and prevented dissemination of demyelination. The effects of PTx icv warrants further investigation and provides an attractive template for further study regarding the pleotropic effects of infectious elements such as PTx in the pathogenesis of autoimmune disorders.     

成年斑马鱼脊髓损伤修复中脑gdnf和nos基因的表达

成年斑马鱼(Danio rerio)具有很强的脊髓损伤后自主修复的能力, 但目前其机制不明。为了研究斑马鱼中脑组织对脊髓再生的影响, 文章应用成年斑马鱼脊髓损伤模型, 采用实时定量PCR方法和原位杂交技术, 检测了斑马鱼脑中胶质细胞源性神经营养因子(gdnf)和一氧化氮合酶(nos)基因在脊髓损伤后4 h、12 h、6 d、11 d的表达情况, 展示了这两种基因在斑马鱼脑内不同核团的动态表达变化。结果显示, 成年斑马鱼脊髓损伤后, 神经营养因子gdnf基因在损伤急性期(4 h、12 h)和神经修复期(6 d、11 d)于斑马鱼脑内呈现显著性升高(P<0.05),而一氧化氮合酶基因nos的表达于损伤急性期显著性升高 (P<0.05), 随后下降, 并在修复期 (11 d)显著降低(P<0.05)。这表明, 脊髓损伤后, 高表达gdnf基因同时低表达nos基因的脑环境给脊髓损伤提供了良好的神经再生微环境, 从而可能促进轴突的再生长及运动能力的恢复。     

Spontaneous and Experimental Neuritis and the Distribution of the Myelin Protein P2 in the Nervous System

The P2 contents of nervous tissues from the human, rabbit, guinea pig, and Lewis rat were measured by radioimmunoassay. The ventral spinal roots contained more P2 than any other tissue. Human dorsal roots and peripheral nerves contained 41-65% of the amount in human ventral roots. Human olfactory and optic nerves and brain contained 1.1-2.7%, spinal cord, 2.8%, cranial nerve VIII, 11%, and cerebral grey matter, 0%. The relative amounts in the rabbit nervous system were similar except that the spinal cord contained 20% of the amount in the ventral roots. Qualitative estimates in the guinea pig showed that the spinal roots and peripheral nerves contained more P2 than the spinal cord, and that none was present in the brain. In the Lewis rat, P2 could be detected in the spinal roots and peripheral nerves but not in the CNS. The distribution of P2 in the human nervous system parallels the incidence and severity of lesions in acute polyradiculoneuritis. It also explains the absence of any lesions in the CNS when experimental allergic neuritis is induced in the Lewis rat.     

Ornithodiplostomum ptychocheilus: migration to the brain of the fish intermediate host, Pimephales promelas.

Migration of cercariae of the diplostomatid trematode, Ornithodiplostomum ptychocheilus, to the brain of the fathead minnow, Pimephales promelas, takes place via directed, nonrandom movement. Penetration of the fish epidermis is rapid and is essentially complete by 2 hr postinfection. Migration to the central nervous system occurs almost exclusively via the general body musculature and connective tissue, although a few cercariae gain direct access to the nervous system via the eyes. Cercariae enter either the neural canal and spinal cord, or the brain via the spinal or cranial nerves and their associated foramina, although cercariae appear to remain in (on) these peripheral nerves for only a short time. Cercariae associated with cranial nerves continue to the brain. Those becoming associated with spinal nerves travel up the neural canal and (or) spinal cord to the brain. Data suggest that most arrive at the brain via the neural canal and spinal cord. Within the brain, most developing metacercariae (neascus-type) occur in the optic lobes and cerebellum. Whether this is “selective localization” or merely the result of the larger space afforded by these brain regions could not be determined.     

原发性干燥综合征患者神经系统病变的临床研究

目的：探讨原发性干燥综合征患者合并神经系统损害的发生率,并分析其出现外周和中枢神经系统受累的临床特点。方法：共纳入34例原发性干燥综合征患者,进行神经系统查体,头MRI、脑脊液化验以及电生理检查。结果：34例患者有15例出现神经系统症状,其中11例表现为外周神经受累,分别为3例颅神经受累,6例多发神经病变,1例多发单神经炎,1例怀疑小纤维神经病;4例为中枢神经受累,分别为．1例患者头和脊髓多发脱髓鞘病变,2例大脑单个灶性病变,1例脑干病变。患者间免疫学检查未见显著差异。结论：原发性干燥综合征患者合并神经系统病变的发生率约为44．1％,外周神经损伤尤其是感觉神经损伤更常见,未发现特异性神经系统改变。与不伴神经系统病变的原发性干燥综合征患者相比较,未发现显著的差异以及能够辅助诊断的实验室检查结果。     

P-glycoprotein (Mdr1a/1b) and breast cancer resistance protein (Bcrp) decrease the uptake of hydrophobic alkyl triphenylphosphonium cations by the brain

Background

Mitochondrial dysfunction contributes to degenerative neurological disorders, consequently there is a need for mitochondria-targeted therapies that are effective within the brain. One approach to deliver pharmacophores is by conjugation to the lipophilic triphenylphosphonium (TPP) cation that accumulates in mitochondria driven by the membrane potential. While this approach has delivered TPP-conjugated compounds to the brain, the amounts taken up are lower than by other organs.

Methods

To discover why uptake of hydrophobic TPP compounds by the brain is relatively poor, we assessed the role of the P-glycoprotein (Mdr1a/b) and breast cancer resistance protein (Bcrp) ATP binding cassette (ABC) transporters, which drive the efflux of lipophilic compounds from the brain thereby restricting the uptake of lipophilic drugs. We used a triple transgenic mouse model lacking two isoforms of P-glycoprotein (Mdr1a/1b) and the Bcrp.

Results

There was a significant increase in the uptake into the brain of two hydrophobic TPP compounds, MitoQ and MitoF, in the triple transgenics following intra venous (IV) administration compared to control mice. Greater amounts of the hydrophobic TPP compounds were also retained in the liver of transgenic mice compared to controls. The uptake into the heart, white fat, muscle and kidneys was comparable between the transgenic mice and controls.

Conclusion

Efflux of hydrophobic TPP compounds by ABC transporters contributes to their lowered uptake into the brain and liver.

General significance

These findings suggest that strategies to bypass ABC transporters in the BBB will enhance delivery of mitochondria-targeted antioxidants, probes and pharmacophores to the brain.     

Prevalence of foot conditions in a geriatric population and their impact on mobility, gait and tendency to falls

Introduction

Foot disease is common among the elderly. Little is known about its prevalence and impact over mobility, gait and tendency to fall.

Material and methods

A geriatric history was taken from 171 women living in a long-term care facility. Photographs were taken of the feet and evaluated by an orthopaedic surgeon and a dermatologist. A multivariate analysis was made to assess de effect of the independent variables over mobility, gait and tendency to fall.

Results

The foot diseases most commonly found were hammer toes (122), callus (79) and peripheral vascular disease (74). Hallux rigidus (OR 24.897, 95% CI, 1.231-503.542) and peripheral vascular disease (OR 2.481, 95% CI, 1.095-5.623) seemed to be associated with changes in gait; both where associated with dependency on instrumental activities of daily living (OR 44.166, 95% CI, 2.402-812.233, and OR 2.659, 95% CI, 1.069-6.615). Hallux rigidus was related to falls (OR 19.27, 95% CI, 1.102-337.26). Tinea pedis was associated with dependency in activities of daily living (OR 11.52, 95% CI, 1.325-100.125).

Conclusions

Foot disorders are common in the elderly. Only hallux rigidus and peripheral vascular disease had an impact on function and gait.     

Mitochondrial dysfunction and complications associated with diabetes

Background

Diabetes is a metabolic syndrome that results in chronically increased blood glucose (hyperglycaemia) due to defects either in insulin secretion consequent to the loss of beta cells in the pancreas (type 1) or to loss of insulin sensitivity in target organs in the presence of normal insulin secretion (type 2). Long term hyperglycaemia can lead to a number of serious health-threatening pathologies, or complications, especially in the kidney, heart, retina and peripheral nervous system.

Scope of review

Here we summarise the current literature on the role of the mitochondria in complications associated with diabetes, and the limitations and potential of rodent models to explore new modalities to limit complication severity.

Major conclusions

Prolonged hyperglycaemia results in perturbation of catabolic pathways and in an over-production of ROS by the mitochondria, which in turn may play a role in the development of diabetic complications. Furthermore, current models don't offer a comprehensive recapitulation of these complications.

General significance

The onset of complications associated with type 1 diabetes can be varied, even with tightly controlled blood glucose levels. The potential role of inherited, mild mitochondrial dysfunction in accelerating diabetic complications, both in type 1 and 2 diabetes, remains unexplored. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.     

Spinal cord injuries: making the re-connection

Why is it that the skin and other tissues and organs can repair themselves, yet the spinal cord and brain cannot? Even more intriguingly, how is it that peripheral nerve damage may be repairable, yet central nervous system damage is not? Molecular answers to these questions could lead to therapies that would heal a damaged spinal cord.