< PreviousExp Neurobiol 2015; 24(4): 257~370Next >
  • Review Article | December 30, 2015

    Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications

    Heejeong Yoo

    Autism spectrum disorder (ASD) is one of the most complex behavioral disorders with a strong genetic influence. The objectives of this article are to review the current status of genetic research in ASD, and to provide information regarding the potential candidate genes, mutations, and genetic loci possibly related to pathogenesis in ASD. Investigations on monogenic causes of ASD, candidate genes among common variants, rare de novo mutations, and copy number variations are reviewed. The current possible clinical applications of the genetic knowledge and their future possibilities are highlighted.

  • Review Article | December 30, 2015

    Characteristics of Brains in Autism Spectrum Disorder: Structure, Function and Connectivity across the Lifespan

    Sungji Ha, In-Jung Sohn, Namwook Kim, Hyeon Jeong Sim and Keun-Ah Cheon

    Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by impaired social communication and restricted and repetitive behaviors (RRBs). Over the past decade, neuroimaging studies have provided considerable insights underlying neurobiological mechanisms of ASD. In this review, we introduce recent findings from brain imaging studies to characterize the brains of ASD across the human lifespan. Results of structural Magnetic Resonance Imaging (MRI) studies dealing with total brain volume, regional brain structure and cortical area are summarized. Using task-based functional MRI (fMRI), many studies have shown dysfunctional activation in critical areas of social communication and RRBs. We also describe several data to show abnormal connectivity in the ASD brains. Finally, we suggest the possible strategies to study ASD brains in the future.

  • Review Article | December 30, 2015

    Exploring the Validity of Valproic Acid Animal Model of Autism

    Darine Froy N. Mabunga, Edson Luck T. Gonzales, Ji-woon Kim, Ki Chan Kim and Chan Young Shin

    The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD.

  • Review Article | December 30, 2015

    New Therapeutic Options for Autism Spectrum Disorder: Experimental Evidences

    Olga Peñagarikano*

    Autism spectrum disorder (ASD) is characterized by impairment in two behavioral domains: social interaction/communication together with the presence of stereotyped behaviors and restricted interests. The heterogeneity in the phenotype among patients and the complex etiology of the disorder have long impeded the advancement of the development of successful pharmacotherapies. However, in the recent years, the integration of findings of multiple levels of research, from human genetics to mouse models, have made considerable progress towards the understanding of ASD pathophysiology, allowing the development of more effective targeted drug therapies. The present review discusses the current state of pharmacological research in ASD based on the emerging common pathophysiology signature.

  • Review Article | December 30, 2015

    Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based?

    Seung Yup Lee, Ah Rah Lee, Ram Hwangbo, Juhee Han, Minha Hong and Geon Ho Bahn

    Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.

  • Review Article | December 30, 2015

    The Role of Oxidative Stress in Neurodegenerative Diseases

    Geon Ha Kim, Jieun E. Kim, Sandy Jeong Rhie and Sujung Yoon

    Oxidative stress is induced by an imbalanced redox states, involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system. The brain is one of organs especially vulnerable to the effects of ROS because of its high oxygen demand and its abundance of peroxidation-susceptible lipid cells. Previous studies have demonstrated that oxidative stress plays a central role in a common pathophysiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases, although the results with regard to their efficacy of treating neurodegenerative disease have been inconsistent. In this review, we will discuss the role of oxidative stress in the pathophysiology of neurodegenerative diseases and in vivo measurement of an index of damage by oxidative stress. Moreover, the present knowledge on antioxidant in the treatment of neurodegenerative diseases and future directions will be outlined.

  • Original Article | December 30, 2015

    Rosmarinic Acid Alleviates Neurological Symptoms in the G93A-SOD1 Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

    Ji-Seon Seo, Juli Choi, Yea-Hyun Leem and Pyung-Lim Han

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons in the brain and spinal cord, resulting in paralysis of voluntary skeletal muscles and eventually death, usually within 2~3 years of symptom onset. The pathophysiology mechanism underlying ALS is not yet clearly understood. Moreover the available medication for treating ALS, riluzole, only modestly improves neurological symptoms and increases survival by a few months. Therefore, improved therapeutic strategies are urgently needed. In the present study, we investigated whether rosmarinic acid has a therapeutic potential to alleviate neurological deterioration in the G93A-SOD1 transgenic mouse model of ALS. Treatment of G93A-SOD1 transgenic mice with rosmarinic acid from 7 weeks of age at the dose of 400 mg/kg/day significantly extended survival, and relieved motor function deficits. Specifically, disease onset and symptom progression were delayed by more than one month. These symptomatic improvements were correlated with decreased oxidative stress and reduced neuronal loss in the ventral horns of G93A-SOD1 mice. These results support that rosmarinic acid is a potentially useful supplement for relieving ALS symptoms.

  • Original Article | December 30, 2015

    Pattern of Respiratory Deterioration in Sporadic Amyotrophic Lateral Sclerosis According to Onset Lesion by Using Respiratory Function Tests

    Dong-Gun Kim, Yoon-Ho Hong, Je-Young Shin, Kwang-Woo Lee, Kyung Seok Park, Seung-Yong Seong and Jung-Joon Sung

    Most amyotrophic lateral sclerosis (ALS) patients show focal onset of upper and lower motor neuron signs and spread of symptoms to other regions or the other side clinically. Progression patterns of sporadic ALS are unclear. The aim of this study was to evaluate the pattern of respiratory deterioration in sporadic ALS according to the onset site by using respiratory function tests. Study participants included 63 (42 cervical-onset [C-ALS] and 21 lumbosacral-onset [L-ALS]) ALS patients and 31 healthy controls. We compared respiratory function test parameters among the 3 groups. Age was 57.4±9.6 (mean±SD), 60.8±9, and 60.5±7 years, and there were 28, 15, and 20 male participants, in the C-ALS, L-ALS, and control groups, respectively. Disease duration did not differ between C-ALS and L-ALS patients. Sniff nasal inspiratory pressure (SNIP) was significantly low in C-ALS patients compared with controls. Maximal expiratory pressure (MEP) and forced vital capacity percent predicted (FVC% predicted) were significantly low in C-ALS and L-ALS patients compared with controls. Maximal inspiratory pressure to maximal expiratory pressure (MIP:MEP) ratio did not differ among the 3 groups. Eighteen C-ALS and 5 L-ALS patients were followed up. ΔMIP, ΔMEP, ΔSNIP, ΔPEF, and ΔFVC% predicted were higher in C-ALS than L-ALS patients without statistical significance. Fourteen C-ALS (77.8%) and 3 L-ALS (60%) patients showed a constant MIP:MEP ratio above or below 1 from the first to the last evaluation. Our results suggest that vulnerability of motor neurons in sporadic ALS might follow a topographic gradient.

  • Original Article | December 30, 2015

    The Effect of Donor-Dependent Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells following Focal Cerebral Ischemia in Rats

    Hyung Woo Park, Jong Wook Chang, Yoon Sun Yang, Wonil Oh, Jae Ha Hwang, Dong Gyu Kim and Sun Ha Paek

    Stroke is an ischemic disease caused by clotted vessel-induced cell damage. It is characterized by high morbidity and mortality and is typically treated with a tissue plasminogen activator (tPA). However, this therapy is limited by temporal constraints. Recently, several studies have focused on cell therapy as an alternative treatment. Most researches have used fixed donor cell administration, and hence, the effect of donor-dependent cell administration is unknown. In this study, we administered 3 types of donor-derived human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the ischemic boundary zone of the ischemic stroke rat model. We then performed functional and pathological characterization using rotarod, the limb placement test, and immunofluorescent staining. We observed a significant decrease in neuron number, and notable stroke-like motor dysfunction, as assessed by the rotarod test (~40% decrease in time) and the limb placement test (4.5 point increase) in control rats with ischemic stroke. The neurobehavioral performance of the rats with ischemic stroke that were treated with hUCB-MSCs was significantly better than that of rats in the vehicle-injected control group. Regardless of which donor cells were used, hUCB-MSC transplantation resulted in an accumulation of neuronal progenitor cells, and angiogenic and tissue repair factors in the ischemic boundary zone. The neurogenic and angiogenic profiles of the 3 types of hUCB-MSCs were very similar. Our results suggest that intraparenchymal administration of hUCB-MSCs results in significant therapeutic effects in the ischemic brain regardless of the type of donor.

  • Case Report | December 30, 2015

    Intracranial Vasospasm without Intracranial Hemorrhage due to Acute Spontaneous Spinal Subdural Hematoma

    Jung-Hwan Oh, Seung-Joo Jwa, Tae Ki Yang, Chang Sub Lee, Kyungmi Oh and Ji-Hoon Kang

    Spontaneous spinal subdural hematoma (SDH) is very rare. Furthermore, intracranial vasospasm (ICVS) associated with spinal hemorrhage has been very rarely reported. We present an ICVS case without intracranial hemorrhage following SDH. A 41-year-old woman was admitted to our hospital with a complaint of severe headache. Multiple intracranial vasospasms were noted on a brain CT angiogram and transfemoral cerebral angiography. However, intracranial hemorrhage was not revealed by brain MRI or CT. On day 3 after admission, weakness of both legs and urinary incontinence developed. Spine MRI showed C7~T6 spinal cord compression due to hyperacute stage of SDH. After hematoma evacuation, her symptoms gradually improved. We suggest that spinal cord evaluation should be considered in patients with headache who have ICVS, although intracranial hemorrhage would not be visible in brain images.