Ramón Martínez-Mármol1, Mercè Salla-Martret2, Daniel Sastre2, Irene Estadella2, Antonio Felipe2*

1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
2Molecular Physiology laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, Spain

 The adult mammalian brain contains neural stem cells (NSCs) that generate neurons and glial cells throughout the lifetime of an organism. NSCs reside in at least two germinal epithelium regions of the adult brain, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the hippocampus. Newborn neurons incorporate into the existing functional networks and play important innate and adaptive roles in cognition, behavior and tissue repair1,2. The identity of particular neural stem cells that generate different classes of neurons and glia, as well as the molecular mechanisms that governs this process in vivo, is a subject of extensive research and debate. Epidermal Growth Factor Receptor (EGFR) activation is one of the most important pathways controlling neural stem cell number and self-renewal3,4. On the other hand, the Shaker-type delayed rectifier K+ channel Kv1.3 functions during cell proliferation, differentiation and migration in many cell types5. This channel is expressed in brain progenitor cells where participates in modulating their final fate. This review summarizes the major findings concerning Kv1.3 and neural stem cell modulation, emphasizing the combination of Kv1.3 with EGFR as promising pharmacological targets against autoimmune neuro-degenerative diseases.

DOI: 10.29245/2572.942X/2016/5.1034 View / Download Pdf

Masashi Kanayama1, Mari L. Shinohara2*

1Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA
2Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA

 Abstract Autoimmune diseases of the central nervous system (CNS), such as multiple sclerosis (MS), are characterized by infiltration of pathogenic immune cells in the CNS. Cells infiltrated in the CNS express pro-inflammatory molecules and cause demyelination. The direct impact of lung immune responses was not previously considered in the pathogenesis of CNS inflammation. However, it recently became clear that the lung acts as a hub organ of pathogenic T cells that are migrating to the CNS. More recent studies further showed that inflamed lung has a critical impact on autoimmune CNS inflammation. Here, we discuss the contribution of the lung in the pathogenesis of CNS autoimmune diseases based on recent reports.

DOI: 10.29245/2572.942X/2016/5.1049 View / Download Pdf

Eduardo NC Bergamaschi1, Fernanda C Nunes2,3, Victor W de Oliveira3, Alessandra Laitart3, Maria L Benevides3, Jean C Nunes2,3*

1Serviço de Neurologia, Departamento de Clínica Médica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
2Neurodiagnostic Brasil, Diagnósticos em Neuropatologia, Florianópolis, SC, Brazil.
3Division of Neuropathology, Hospital Universitário (HU), UFSC, Florianópolis, SC, Brazil.

 Pain is a common and often disabling symptom in Parkinson’s disease (PD) which has received increasing attention in recent years. Headache represents a common form of pain among the general population, but there are few studies on this symptom in PD. In 2014, our group reported a lower prevalence of headache in PD patients compared to the general population, as well as an association between the predominant side of headache and the side of initial motor signs of PD. Since then, there has been few new data on the specific issue of headache in PD patients, though several recent studies have contributed to the understanding of pain in PD, both in terms of clinical and pathophysiological aspects, including new observations on pain association with side of motor symptom onset. Here, we review those studies, and re-discuss our own findings in comparison to the current information available. A better comprehension of pain physiology in PD could facilitate the development of new therapeutic approaches, thus providing a better quality of life for PD patients.

DOI: 10.29245/2572.942X/2016/5.1051 View / Download Pdf

Becker L1, Kutz DF2, Voelcker-Rehage C1*

1Institute of Human Movement Science and Health, Sports Psychology, Technische Universität Chemnitz, Thüringer Weg 11, 09126 Chemnitz, Germany
2Institute of Human Movement Science and Health, Theory and Practice of Sports, Technische Universität Chemnitz, Thüringer Weg 11, 09126 Chemnitz, Germany

DOI: 10.29245/2572.942X/2016/5.1044 View / Download Pdf

Robert C.A.M. van Waardenburg*

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham AL, USA

 Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H493R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex. The ATM kinase activates proteins early on in response to DNA damage. Tdp1-/- and Atm-/- mice exhibit accumulation of DNA topoisomerase I-DNA covalent complexes (TOPO1-cc) explicitly in neuronal tissue during development. TDP1 resolves 3’- and 5’-DNA adducts including trapped TOPO1-cc and TOPO1 protease resistant peptide-DNA complex. ATM appears to regulate the response to TOPO1-cc via a noncanonical function by regulating SUMO/ubiquitin-mediated TOPO1 degradation. In conclusion, TDP1 and ATM are critical factors for neuronal cell viability via two independent but cooperative pathways.

DOI: 10.29245/2572.942X/2016/5.1048 View / Download Pdf

Yun-Tian Shen1, Ying Yuan1,2, Wen-Feng Su1, Yun Gu1, Gang Chen1*

1Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
2Affiliated Hospital of Nantong University, Nantong, China

 The myelin sheath wraps axons is an intricate process required for rapid conduction of nerve impulses, which is formed by two kinds of glial cells, oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Myelin biogenesis is a complex and finely regulated process and accumulating evidence suggests that myelin protein synthesis, storage and transportation are key elements of myelination, however the mechanisms of regulating myelin protein trafficking are still not very clear. Recently, the evidences of lysosomal exocytosis in oligodendrocytes and Schwann cells are involved in regulated myelination have emerged. In this paper, we briefly summarize how the major myelin-resident protein, as proteolipid protein in the central nervous system and P0 in the peripheral nervous system, transport from lysosome to cell surface to form myelin sheath and focus on the possible mechanisms involved in these processes. Advances in our understanding of glia, as well as new tools engineering, will further improve the knowing of myelin biogenesis.

DOI: 10.29245/2572.942X/2016/5.1047 View / Download Pdf

Esther A. Pelzer1,2*, Lars Timmermann2, Marc Tittgemeyer1

1Translational Neurocirciutry Group, Max-Planck Institute for Metabolism Research Cologne, Cologne, German
2Department of Neurology, University Clinics Cologne, Cologne, Germany

 Subcortical communication is an important underlying feature for the smooth performance of motor behaviour. Especially movement disorders like Parkinson’s disease show impairment in the basal-ganglio-thalamic and cerebello-thalamic communication; but also an impairment of the direct communication between these two structures has been proposed.

In this review we highlight important clinical findings concerning the pathological communication between these subcortical structures; additionally we propose a new hypothesis in the development of neurodegenerative disease: we assume that axon degeneration is crucially implicated in the development of parkinsonian symptoms and link the current findings to the development of pathological oscillatory activity. New techniques like probabilistic tractography now offer the possibility to in vivo measure axon degeneration by the determination of connectivity decline and allow the combination with electrophysiological recording. We hypothesize that a change in frequency bands in oscillatory activity might be a product of underlying axonal degeneration; moreover axonal degeneration might be worsened by pathological oscillatory activity resulting in a vicious circle. The thalamus, as main relay station between the basal ganglia and the cerebellum seems to be involved in this disease pathology in Parkinson’s disease.

DOI: 10.29245/2572.942X/2016/5.1041 View / Download Pdf

Willemieke M. Kouwenhoven and Marten P. Smidt*

Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands


 Two essential monoaminergic neurotransmitter systems are located within the midbrain and the hindbrain region: the mesodiencephalic dopaminergic (mdDA) neurons, which can be divided in the substantia nigra (SN), the ventral tegmental area (VTA), and the serotonergic (5-HT) neurons. In the adult brain these two types of monoaminergic neurons are critical to our neurological health. Dysfunction of the mdDA system has been associated with schizophrenia and Parkinson's Disease (PD), while dysfunction of the 5HT system has in turn been associated with psychiatric diseases such as depression and autism. The homeobox transcription factor Engrailed 1 (En1) is expressed in both types monoaminergic neurons, and is required for the correct programming and survival of the mdDA and 5HT neurons. Recently, we reported on the dual role of En1 in both neurotransmitter systems through its central role in the maintenance of the Isthmic Organizer, which is the embryonic signaling center that instructs and separates dopaminergic and serotonergic neuronal development.

DOI: 10.29245/2572.942X/2016/5.1036 View / Download Pdf

Rodger J. Elble

Department of Neurology, Southern Illinois University School of Medicine, Springfield, USA

The Essential Tremor Rating Assessment Scale was developed by the Tremor Research Group (www.tremorresearchgroup.org) to quantify essential tremor severity and its impact on activities of daily living. This scale requires only a pen and paper, and can be completed in about 10 minutes. Upper extremity action tremor is the main focus of this scale, but action tremor is also assessed in the head, face, voice, and lower limbs. The scale has excellent face validity, inter- and intra-rater reliability, and sensitivity to change. The activities of daily living section correlates strongly with the performance section, and this scale also correlates strongly with transducer measures of tremor and with the Fahn-Tolosa-Marín tremor rating scale. In the Fahn-Tolosa-Marín tremor rating scale, upper extremity tremor greater than 4 cm corresponds to a maximum rating of 4, while grade 4 tremor in the Essential Tremor Rating Assessment Scale corresponds to an amplitude greater than 20 cm. Therefore, the Essential Tremor Rating Assessment Scale is better suited for assessment of severe essential tremor.

DOI: 10.29245/2572.942X/2016/4.1038 View / Download Pdf

Cong-Cong Qi1,2, Yu-Qiang Ding1, Jiang-Ning Zhou2*

1Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai 200120, China
2CAS Key Laboratory of Brain Function and Diseases, School of Life Science, University of Science and Technology of China, Hefei 230027, Anhui, China

The forced swim test (FST), originally developed by Porsolt et al., is highly valuable for assessing the antidepressant-like effects of the majority of currently-available antidepressants. Lucki et al. modified some parameters of the traditional FST in order to facilitate the differentiation between serotonergic and noradrenergic classes of antidepressant drugs. In addition, the FST is one of the most commonly used models for assessing antidepressant-like behaviors in both rats and mice. Focus on the present neuroscience field, knockout and transgenic mice provide a tool for assessing the mechanisms of action of antidepressants, and the factors influencing these behavior in the FST should be taken into considerations. In this MiniReview, we reviewed several biological factors (e.g. strain, gender, age, susceptibility) that may in?uence mice behavior in the FST and attempt to describe those variables that should be considered when designing studies employing the FST.

DOI: 10.29245/2572.942X/2016/4.1033 View / Download Pdf

Katz D1,2, Katz I1,2, Shoenfeld Y1,3*

1The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel
2Faculty of Medicine, The Hebrew University of Jerusalem, Israel
3Incumbent of the Laura Schwarz-kipp chair for research of autoimmune diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel

DOI: 10.29245/2572.942X/2016/4.1017 View / Download Pdf

Homajoun Maslehaty1*, Arya Nabavi2, Hubertus Maximilian Mehdorn2

1Department of Neurosurgery, University Hospitals Essen, Germany
2Department of Neurosurgery, University Hospitals Schleswig-Holstein, Kiel, Germany

DOI: 10.29245/2572.942X/2016/4.1009 View / Download Pdf

Jonathan T. Blackmon1, Toni Viator RN2, Robert M. Conry3*

1Covenant College, USA
2University of Alabama at Birmingham, USA
3Division of Hematology Oncology, University of Alabama at Birmingham, USA

Immune checkpoint inhibitors (CPIs) which unleash suppressed antitumor immune responses are revolutionizing the systemic treatment of cancer. Durable responses and prolongation of survival come at a price of frequent immune-related adverse events resulting from inflammation of normal tissues. Herein, we review serious central nervous system (CNS) toxicities of immune CPIs including ipilimumab, nivolumab, pembrolizumab and atezolizumab. Case reports of 20 patients with CPI-associated encephalitis, meningitis, or myelitis were reviewed as well as data from large scale registration trials. The overall incidence of serious immune-related CNS toxicities is approximately 0.4-1% with the potential for hundreds of cases annually in the United States. Patients suspected of having serious CPI-associated CNS toxicity should have a neurology consult, lumbar puncture, and MRI of the affected regions. If confirmed, the offending drug should be permanently discontinued and high dose intravenous steroids initiated, preferably with 500-1,000 mg of methylprednisolone daily. With timely diagnosis and appropriate management, the majority of patients experience complete neurologic recovery. As the array of indications for CPIs rapidly increases, it is imperative for clinicians to have a high index of suspicion for immune-related CNS toxicities.

DOI: 10.29245/2572.942X/2016/4.1040 View / Download Pdf

Alma Rystedt1, Kerstin Brismar2, Sten-Magnus Aquilonius3, Hans Naver4, Carl Swartling1,5*

1Hidrosis Clinic, Stockholm, Sweden
2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
3Department of Neuroscience, Neurology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
4Department of Internal Medicine, Neurology, Nyköping Hospital, Nyköping, Sweden
5Department of Medical Sciences, Dermatology and Venereology, Uppsala University, Uppsala, Sweden

Hyperhidrosis is a social, emotional and occupational disability which affects close to 3 % of the population. Patients with hyperhidrosis suffer an extremely negative impact on their quality of life on a par with being severely affected by psoriasis. Most of the sufferers have the primary genetic form of hyperhidrosis. Secondary hyperhidrosis can often be omitted based on anamnestic data, but sometimes further examinations must be performed.

Topical treatment (e.g. aluminium chloride) is the first choice for localised hyperhidrosis. Botulinum toxin, iontophoresis, microwave thermolysis (miraDry®), and/or systemic medications are indicated if topical treatment is insufficient or not applicable. Endoscopic Thoracic Sympathectomy (ETS) is no longer performed in Sweden due to the serious side effects profile. In countries where ETS still is performed, patients must be carefully selected and educated to fully understand the possibility of limited efficacy and the risks of complications including, but not limited to, compensatory sweating. This treatment should be the last option.

Examination- and treatment recommendations based on international guidelines and literature are presented in this review.

DOI: 10.29245/2572.942X/2016/4.1037 View / Download Pdf

Qing Lu, Stephen M. Black

Department of Medicine, University of Arizona, AZ, USA

The neuronal cell death associated with perinatal asphyxia, or hypoxic-ischemic (HI) brain injury, plays an important role in neonatal mortality and neurodevelopment retardation. The types of cell death associated with HI in the brain have been classified as being either apoptotic or necrotic. Here we describe the recent discoveries of multiple non-apoptotic cell death pathways: necroptosis; ferroptosis; and autosis (autophagy). These new cell death pathways expand our understanding of the mechanisms underlying the cell death associated with perinatal asphyxia. By targeting specific regulators of these pathways, new therapies may be developed that could protect the neonatal brain from the HI mediated injury.

DOI: 10.29245/2572.942X/2016/4.1035 View / Download Pdf

So Mi Lee1,2, In-One Kim1

1Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
2Department of Radiology, Kyungpook National University Medical Center, Daegu, Korea

Germ cell tumor (GCT) arising in the basal ganglia or thalami is relatively uncommon. It occurs most commonly in boys during second decade of life. It is difficult to diagnose early stage GCTs in these regions because the images are not so typical and the symptom onset is insidious. However, early diagnosis of this tumor is important because of the high radiosensitivity and potential curability. Early stage GCTs originating from the basal ganglia or thalami appear as ill-defined small patchy lesions. They frequently present as hyperintense lesions compared with deep gray matter on T2-weighted image without cyst, mass effect, or prominent enhancement. Microhemorrhages can be accompanied infrequently. These tumors are mostly associated with ipsilateral hemiatrophy at the time of presentation. During tumor progression, tiny cysts develop at a relatively early stage, and intratumoral cyst, hemorrhage, and ipsilateral hemiatrophy gradually tend to be more pronounced. Ultimately, these become overt large mass with remarkable heterogenous enhancement, containing multiple cysts of various sizes and hemorrhage. This review aims to describe the serial MR imaging findings of the GCTs arising from basal ganglia or thalami, focusing on the early finding.

DOI: 10.29245/2572.942X/2016/4.1039 View / Download Pdf

Jyotshna Kanungo*

Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA

Alzheimer’s disease (AD) is characterized by neuronal death with an accumulation of intra-cellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. Reduced DNA repair ability has been reported in AD brains. In neurons, the predominant mechanism to repair double-strand DNA breaks (DSB) is non-homologous end joining (NHEJ) that requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD DNA-PK catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 (Ku80) and p70 (Ku70) subunits. Upon binding to double-stranded DNA ends, Ku recruits DNA-PKcs to process NHEJ. In AD brains, reduced NHEJ activity as well as DNA-PKcs and Ku protein levels have been shown. Normal aging brains also show a reduction in both DNA-PKcs and Ku levels questioning a direct link between NHEJ ability and AD, and suggesting additional players/events in AD pathogenesis. Deficiency of Ku80, a somatostatin receptor, can disrupt somatostatin signaling thus inducing amyloid beta (Aβ) generation, which in turn can potentiate DNA-PKcs degradation and consequently loss of NHEJ activity, an additional step negatively affecting DSB repair. Trigger of these two different pathways culminating in genome instability may differentiate the outcomes between AD and normal aging.

DOI: 10.29245/2572.942X/2016/3.1016 View / Download Pdf

Gonzalo Flores1 and Julio Morales-Medina2

1Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, Puebla, México
2Centro de Investigación en Reproducción Animal, CINVESTAV- Universidad Autónoma de Tlaxcala, AP 62, CP 90000, Tlaxcala, México

Schizophrenia is a complex mental disorder that starts at early adulthood with a combination of positive and negative symptoms as well as cognitive impairments. It is well known that dendritic spine density and dendritic length of the pyramidal neurons of the prefrontal cortex (PFC) are reduced in the post-mortem tissue of schizophrenia pateints. In addition, the volume of the PFC is reduced in this mental disorder. A possible hypothesis for these morphological changes suggests that the disruption between PFC and hippocampus, at an early age is involved in the pathophysiology of schizophrenia. Furthermore, rats with bilateral lesion of the neonatal ventral hippocampus (nVHL) at an early age is an example of the initial disruption between hippocampus and PFC and also exhibits a reduction in the synaptic connections in the PFC. The present mini-review discusses the neurochemical and morphological changes in the PFC of rats that underwent nVHL, an animal model of schizophrenia.

DOI: 10.29245/2572.942X/2016/3.1024 View / Download Pdf

Silvia Campioni1,2, Roland Riek1*

1Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Vladimir-Prelog-Veg 2, 8093 Zurich, Switzerland
2Laboratory of Food and Soft Materials, Department of Health Sciences and Technologies, Swiss Federal Institute of Technology Zurich, Schmelzbergstrasse 9, 8092 Zurich, Switzerland

Despite extensive research, a detailed description of the physiological function of α-Synuclein (α-Syn), the human neuronal protein involved in the pathogenesis of Parkinson’s Disease, is still lacking, most likely due to its highly dynamic conformation and behaviour. Recently, it has become increasingly evident that the interaction of α-Syn with membranes plays an important role in its function and misfunction. Strikingly, despite not having a membrane scaffolding domain, α-Syn can extensively reshape membrane bilayers. Moreover, stable and soluble nanometer-sized particles, whose morphology is ranging from tubules to discoids, can be obtained in vitro with different protocols and from different lipids. The focus of this review article is on the description of the membrane remodelling activity of α-Syn and on its possible physiological role.

DOI: 10.29245/2572.942X/2016/3.1031 View / Download Pdf

Patrick L. McGeer* Edith G. McGeer and Moonhee Lee

Kinsmen Laboratory of Neurological Research, University of British Columbia, VancouverBC V6T 1Z3, Canada

Sodium thiosulfate (STS) is an industrial chemical which also has a long medical history. It was originally used as an intravenous medication for metal poisoning. It has since been approved for the treatment of certain rare medical conditions. These include cyanide poisoning, calciphylaxis, and cisplatin toxicity. In vitro assays have demonstrated that it is an anti-inflammatory and neuroprotective agent. It therefore has potential for treating neurodegenerative diseases such as Alzheimer disease and Parkinson disease. NaSH has similar properties and is somewhat more powerful than STS in these in vitro assays. However STS has already been approved as an orally available treatment. STS may therefore be a readily available candidate for treating neurodegenerative disorders such as Alzheimer disease and Parkinson disease.

DOI: 10.29245/2572.942X/2016/3.1032 View / Download Pdf

Jianli Niu and Pappachan E. Kolattukudy*

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA

Inflammatory response represents one of the first immune processes following injury. However, evidence indicates that inflammatory response can also induce cellular protection associated with preconditioning, a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. The elucidation of mechanisms that allow inflammatory response to confer cellular protection is critical to developing new therapeutic strategies against acute ischemic insults. In the present review, we will give a short overview on a novel zinc-finger protein, MCPIP (also known as Zc3h12a or Regnase-1), which may function as a master integrator of endogenous cellular protection exerted by preconditioning.

DOI: 10.29245/2572.942X/2016/3.1026 View / Download Pdf

Alex Steimle and Julia-Stefanie Frick*

Institute of Medical Microbiology and Hygiene, University of Tuebingen, Tübingen, Germany

In recent years, a growing interest in pathophysiological processes that are associated with the endosomal and lysosomal protease cathepsin S (CTSS) results in an increasing number of various published methods for CTSS activity detection. CTSS has been reported to be involved in the pathology of autoimmune diseases like multiple sclerosis as well as in tumor growth and Alzheimer’s disease. These implications make this enzyme a first class drug target. In order to fully understand the involvement of CTSS in the formation of pathological processes, gene and protein expression analysis is not sufficient. Rather, one should focus on the regulation of its enzymatic activity. Different approaches for CTSS activity detection are available and described. However, some of these approaches are not suitable for a standard laboratory without special equipment or technical expertise or provide other limitations. We have recently published an easy-to-perform protocol for reliable, quantifiable and reproducible CTSS activity detection. In this review we want to discuss our application and compare it with other published methods and protocols. This might help researchers who are interested in CTSS research to decide which application fits best to their technical or personal facilities.

DOI: 10.29245/2572.942X/2016/3.1023 View / Download Pdf

Ana Velasco* and Maruan Hijazi

Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain

Down syndrome (DS): or trisomy 21: is the most common autosomal aneuploidy and the leading genetic cause of intellectual disability. It is widely established that mental retardation is primarily a consequence of brain functioning and developmental abnormalities in neurogenesis. Some changes in the physical structure of the dendrites are a major cause of impaired synaptic plasticity of DS. The overexpression of the dual specificyty tyrsone phosphorylation-regulated kinase 1A (DYRK1A): located on chromosome 21: is involved in cellular plasticity and responsible for central nervous system disturbance in DS.

Oleic acid is a neurotrophic factor that promotes neuronal differentiation and increases the levels of choline acetyltransferase (ChAT). Furthermore: it has recently been shown that it induces migration and formation of new synapses in euploid cells. However: remarkably oleic acid fails to reproduce the same effects in trisomic cells.

Here we review the hypothesis that oleic acid-dependent synaptic plasticity may be dependent on the lipid environment. Thus: differences in membrane composition may be essential to understand why oleic acid promotes higher cell plasticity in euploid than in trisomic cells.

DOI: 10.29245/2572.942X/2016/3.1029 View / Download Pdf

Lorna Guéniot1a, Claire Latroche1ab, Cédric Thépenier1,2a, Laurent Chatre3,4, Aurélien Mazeraud1, Daniel Fiole1,2, Pierre L. Goossens1, Fabrice Chrétien1,5,6c and Gregory Jouvion1,5c

1Institut Pasteur, Histopathologie Humaine et Modèles Animaux, Paris, France
2Institut de Recherche Biomédicale des Armées, Interactions Hôte-Agents Pathogènes, Brétigny-sur-Orge, France
3Groupe Stabilité de l’ADN Nucléaire et Mitochondrial, CNRS UMR 3525, Paris, France
4Institut Pasteur, Cellules Souches et Développement, Paris, France
5Université Paris Descartes, PRES Sorbonne-Paris-Cité, Paris, France
6CH Sainte-Anne, Neuropathology Department, Paris, France
aGuéniot L, Latroche C, and Thépenier C contributed equally to this work
bPresent address: San Raffaele Telethon Institute for Gene Therapy; Division of Regenerative Medicine, Stem Cells and Gene Therapy; San Raffaele Scientific Institute; Milano, Italia.
cChrétien F and Jouvion G share senior co-authorship

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, caused by absence of functional dystrophin and inevitably leading to death. A variable proportion of women carriers (2.5 to 19%) can also manifest symptoms ranging from myalgia to cardiomyopathy, and pathophysiological mechanisms are still not completely understood. Our study focused on 12 month-old female mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD. Our aim was to focus on the alterations of the vascular network organisation, and functional repercussions using a combination of histology/morphometry techniques and totally non-invasive functional approach (multiparametric and functional nuclear magnetic resonance), clearly relevant for clinical diagnosis and research, combining arterial spin labeling imaging of perfusion, and 31P-spectroscopy of phosphocreatine kinetics. Collectively, our results demonstrate that the vasculature, both in its steady state organisation and dynamic behaviour after an ischemia-reperfusion stress, is altered in the 12 month-old female mdx mouse: increased density of vascular sections in histology, modification of the post-ischemic hyperemia profile, increase in mitochondrial oxidative rephosphorylation capacity, in striking opposition to what was observed in age-matched male mdx mice. We believe the apparent discordance between vascular and muscular features in the female mdx mouse make it an interesting tool to decipher further dystrophinopathy pathophysiological mechanisms.

DOI: 10.29245/2572.942X/2016/2.1014 View / Download Pdf

J. Leigh Leasure1,2*, Rebecca West1

1Department of Psychology, University of Houston, 126 Heyne Building, Houston, TX 77204-5022, United States
2Department of Biology & Biochemistry, 3455 Cullen Boulevard, Room 342, Houston, TX 77204-5001, United States

Exercise has long been considered a useful means by which to maintain brain health and treat brain diseases. Yet many of the neural benefits of exercise, such as enhanced hippocampal neurogenesis, take weeks to manifest. Moreover, the brains most in need of the restorative effects of exercise are often paired with bodies that can tolerate very little physical activity, such as those deconditioned by stroke. It would therefore be of great utility to pinpoint ways in which the brain benefits of exercise could be augmented without adding additional exercise time. Exercise represents a significant challenge to the brain because of the heat produced by exercising muscles, but physical activity in the cold attenuates this physiological burden. Using a rat model of voluntary exercise, we recently tested the hypothesis that exercise in cold ambient temperature (4.5°C) would stimulate hippocampal neurogenesis more effectively than exercise at room temperature. We found that, compared to animals that ran at room temperature, animals that exercised in the cold ran a shorter distance and for less total time. Nonetheless, they had more significantly more newly generated neurons in the hippocampal dentate gyrus, indicating that running in the cold may be an effective means by which to maximize brain exercise benefits, yet minimize exercise time.

Exercise is increasingly becoming accepted as “medicine” for diseases of both brain and body1. For the brain, exercise offers chemical, cellular and structural benefits, including enhanced generation of new neurons, glia and blood vessels2-5, increased expression of neurotrophins (such as brain-derived neurotrophic factor (BDNF)6,7), dendritic remodeling8,9 and stabilization of stress responses10 and inflammatory signaling11. These mechanisms of action directly counteract those present in disease states. For example, the depressed brain is characterized by decreased synaptic plasticity, hippocampal neurogenesis and BDNF12, all of which can be reversed by exercise.

DOI: 10.29245/2572.942X/2016/2.1027 View / Download Pdf