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Abstract: In recent years, the number of children diagnosed with autism spectrum disorder has increased. Autism is a cognitive impairment that affects the way people socialize and behave. Currently, treatments and services exist mostly for children, even though it is a lifelong disorder and those with it are living longer. Like autism, Alzheimer’s affects a person’s cognitive abilities, although its onset occurs much later in life. With the increased average lifespan due to technological advances, the number of individuals diagnosed with Alzheimer’s is expected to grow exponentially. There are many parallels between the two conditions, and research suggests that Autism may act as a buffer against Alzheimer’s disease. This systematic literature review aims to better describe the link between autism and Alzheimer’s disease, which could further an understanding of each condition individually.
Neuroprotection in Autism, Schizophrenia and Alzheimer's Disease provides an up-to-date overview on recent clinical studies and the similarities discovered in the most prevalent brain disorders. The book's content will help shed light on basic mechanisms and provide new avenues for early diagnosis toward disease prevention and disease modification. It is written for researchers, clinicians and medical physicians in neuroscience, neurology and psychiatry. Sections discuss the shared pathophysiological mechanisms that underlie autism, schizophrenia/mood disorders and Alzheimer’s disease, i.e. neurodevelopmental disorders, neuropsychiatric diseases and neurodegenerative disorders. Offers an up-to-date overview of basic and clinical studies concerning similarities in the most prevalent brain disorders Helps the reader become familiar with novel neuroprotective mechanisms and experimental treatment modalities in these difficult to treat disorders Written for researchers, clinicians and medical physicians in neuroscience, neurology and psychiatry
Part I: Targeted intervention for cognitive impairment identified in the young-adult rat: Behavioral and pharmacological treatments for cognitive impairments associated with the aging process are becoming a growing focus of concern as the elderly population continues to expand worldwide. Studies of cognitive impairment are typically designed to study cognitive decline in aged animals in order to identify molecular changes that occur in the aging brain. However, studies investigating cognitive impairments in young animals and tracking cognition over the lifetime are rare. Furthermore, young rats ubiquitously perform very well on established versions of commonly used paradigms such as the Morris Water Maze (MWM), suggesting that more challenging tasks may be required to reveal subtle differences in young animals. Current evidence suggests that environmental enrichment can improve learning and memory, and is effective at ameliorating symptoms associated with various disease states, but the age at which enrichment can be effective and the length of enrichment necessary remain unclear. Furthermore, the impacts of environmental enrichment on synaptic plasticity and the molecular mechanisms behind environmental enrichment have not been elucidated. A compelling body of evidence suggests that group 1 metabotropic glutamate receptors (mGluR1/5) are vital for hippocampal synaptic plasticity and learning and memory formation, and it has been suggested that this effect is mediated by activation of the extracellular signal related kinase (ERK) and mammalian target of rapamycin (mTOR) pathways. The experiments in this thesis were designed to develop behavioral paradigms sensitive enough to reveal subtle differences in hippocampal dependent learning and memory in young rodents in order to track performance over their lifespan. The experiments were further designed to determine the impact of environmental enrichment on cognition, synaptic plasticity, and mGluR dependent signaling pathways in young-adult rodents. First, we show that a novel one-day version of the Morris water maze and novel object recognition can be used to identify subtle cognitive impairments early in life. We have found that these two tasks reliably separate young rats into inferior and superior learners, are highly correlated, and that performance on these tasks early in life is predictive of performance at 12 months of age. Furthermore, we have found that repeated training in this task selectively improves the performance of inferior learners, suggesting that behavioral training from an early age may provide a buffer against age-related cognitive decline. Second, we show that 4 months of environmental enrichment improves cognitive performance in young-adult rats and enhances hippocampal LTP. We demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Taken together, the results of these studies provide valuable insight into novel means of preventing cognitive impairment by targeting affected populations from a young age. The results of these studies further provide potential molecular mechanisms that may be targeted for cognitive enhancement. In addition to environmental enrichment, gene therapy is a promising therapeutic technique for interventions in numerous disease states. Indeed, AAV has proven to be successful for gene therapy in a number of animal models of disease, and is currently being used in human clinical trials for various conditions such as Lieber congenital amaurosis, hemophilia, muscular dystrophy, Parkinson's disease, and Alzheimer's disease. MRI contrast agents such as gadoteridol have been used to track the distribution of therapeutic drugs in real time, allowing visualization of the volume of spread across various structures. However, the effect of gadoteridol on the spread of the injected drugs has not been thoroughly investigated. In a third study, we conducted experiments to determine whether coinfusion with gadoteridol impacts the spread of rAAV in the injected tissue. We show that rAAV1 but not rAAV5 transduction efficiency is significantly increased by co-infusion with gadoteridol, and that gadoteridol has no deleterious effects on behavior. This provides a safe method to enable targeting of larger brain regions with fewer injection sites and thus reduce surgery time, an important variable to consider especially when working with aged or fragile animal models of neurological disease. Part II: A novel role for the ER membrane acetylCoA transporter AT-1 in the development of autism AcetylCoA is an essential substrate for a wide range of biochemical reactions that occur within the cell. The production of cytosolic acetylCoA relies predominantly on the conversion of citrate from the mitochondria and CoA by ATP-citrate lyase (Acly), and the condensation of free acetate from the peroxisome and CoA by acetylCoA synthetase (AceCS). AcetylCoA is then imported into the lumen of the ER by the ER membrane transporter AT-1 (also known as SLC33A1), where it serves as the donor of the acetyl group in the Nε-lysine acetylation of ER-resident and -transiting proteins. Previous studies form our laboratory have revealed that the ER acetylation machinery regulates two essential and intimately related functions of the ER: (i) "positive" selection of correctly folded nascent polypeptides (as part of quality control) and (ii) tight regulation of autophagy (as part of ER Associated Degradation type II). A balance between these two functions must be maintained to ensure ER homeostasis. The acetylation machinery of the ER has been linked to a variety of human conditions, including hereditary spastic paraplegia, Alzheimer's disease (AD), and Autism spectrum disorder (ASD). In particular, an S113R mutation in AT-1 has been identified in patients with a familial form of spastic paraplegia ΝϚʹ“�� Μρο ιαβ ϝαπ γδκμλπϟοαϟδγ ϟϝαϟ ϟϝζπ κρϟαϟζμλ ζλ ΑϞ�» νοδσδλϟπ γζκδοζφαϟζμλ με ϟϝδ ϟοαλπνμοϟδο αλγ ϐαρπδπ γδϐοδαπδγ ζλειρτ με Αϐδϟυι�μΑ ζλϟμ ϟϝδ ΔΟ� ςϝζϐϝ ιδαγπ ϟμ αβδοοαλϟ ζλγρϐϟζμλ με αρϟμνϝαϛυ ζλ ϐδιιπ αλγ ζλ αλζκαι κμγδιπ� Ϟϝζπ ζλπρεεζϐζδλϐυ με ΑϞ�»ζλ ϟϝδ αλζκαι οδπριϟπ ζλ λδρομγδϛδλδοαϟζμλ� ζλειακκαϟζμλ� αλγ νομνδλπζϟυ ϟμ ζλεδϐϟζμλπ αλγ ϐαλϐδο� Πϟργζδπ εομκ μρο ιαβ ϝασδ αιπμ οδσδαιδγ ϟϝαϟ ϟϝδ αϐϟζσζϟυ με ΑϞ�» αλγ ϟϝδ ΑϞαπδπ αοδ ζλϟζκαϟδιυ ιζλθδγ ϟμ ϟϝδ ναϟϝμϛδλδπζπ με Αιφϝδζκδοπͅ γζπδαπδ� Ϟϝδ αϐϟζσζϟυ με ΑϞ�» οδϛριαϟδπ ϟϝδ αϐδϟυιαϟζμλ πϟαϟρπ με ΒΑ�Δ�»� ϟϝδ οαϟδ� ιζκζϟζλϛ πϟδν ζλ ϟϝδ νομγρϐϟζμλ με Α�ø� Ζλϝζβζϟζμλ με ϟϝδ ΑϞαπδπ ϝαπ βδδλ πϝμςλ ϟμ γζκζλζπϝ ΒΑ�Δ�» ιδσδιπ αλγ ιδαγ ϟμ πρβπδξρδλϟ γδϐοδαπδγ ιδσδιπ με Α�ø� Α�ø αϛϛοδϛαϟδπ� αλγ λδρομλαι νιαξρδπ� Εροϟϝδοκμοδ� ζλϝζβζϟζμλ με ϟϝδ ΑϞαπδπ ϝαπ βδδλ πϝμςλ ϟμ ζκνομσδ πυλανϟζϐ νιαπϟζϐζϟυ� ιδαολζλϛ αλγ κδκμου� αλγ ιζεδπναλ ζλ α κμρπδ κμγδι με ΑΓ� Εζλαιιυ� α γρνιζϐαϟζμλ με ΑϞ�» ϝαπ βδδλ οδνμοϟδγ ζλ ναϟζδλϟπ ςζϟϝ αρϟζπκ πνδϐϟορκ γζπμογδο �ΑΠΓ� αλγ ζλϟδιιδϐϟραι γζπαβζιζϟυ �Αρϟζπκ Γαϟαβαπδ· αιπμ Πςζππϝδικ Θ�� δϟ αι� ΑΠϜϚ Αλλραι Κδδϟζλϛ� Μϐϟμβδο »��““� “«»ʹ� Παλ Γζδϛμ� �Α�� Ϝμςδσδο� ϟϝδ κδϐϝαλζπκπ βδϝζλγ ϟϝζπ ϐμοοδιαϟζμλ αλγ ϝμς ΑϞ�» καυ ϐμλϟοζβρϟδ ϟμ ϟϝδ ναϟϝμϛδλδπζπ με ΑΠΓ αοδ λμϟ ϐιδαο� Ζλ ϟϝζπ ϟϝδπζπ� ςδ πμρϛϝϟ ϟμ ζλσδπϟζϛαϟδ ϟϝδ ϐμλπδξρδλϐδπ με ζλϐοδαπδγ αϐϟζσζϟυ με ΑϞ�»� �δ ϛδλδοαϟδγ αλ ΑϞ�» Ϟϛ κμρπδ κμγδι ϟϝαϟ πδιδϐϟζσδιυ μσδοδτνοδππδπ ΑϞ�» ζλ λδρομλπ� Ϟϝδπδ αλζκαιπ γδκμλπϟοαϟδ ϐμϛλζϟζσδ γδεζϐζϟπ� αρϟζπϟζϐ�ιζθδ πμϐζαι βδϝασζμο� αβδοοαλϟ πυλανϟζϐ νιαπϟζϐζϟυ� ζλϐοδαπδγ γδλγοζϟζϐ πνζλδ αλγ βοαλϐϝ εμοκαϟζμλ� αλγ ςζγδπνοδαγ νομϟδμκζϐ ϐϝαλϛδπ� Ζλ αγγζϟζμλ� ςδ εμρλγ ϟϝαϟ ΑϞ�» Ϟϛ αλζκαιπ γζπνιαυ ζλϐοδαπδγ δτνοδππζμλ με κζϟμϐϝμλγοζαι δλφυκδπ οδιαϟδγ ϟμ αϐδϟυι�μΑ νομγρϐϟζμλ� πρϛϛδπϟζλϛ ϟϝαϟ ζλϐοδαπδγ ειρτ με αϐδϟυι�μΑ ζλϟμ ϟϝδ ΔΟ ϐαρπδπ ϐμκνδλπαϟμου αϐϟζσζϟυ με ϟϝδ κζϟμϐϝμλγοζα�
Author : Institute of Medicine Publisher : National Academies Press Page : 358 pages File Size : 32,66 MB Release : 2008-03-12 Category : Medical ISBN : 0309108810
Autism spectrum disorders (ASD) constitute a major public health problem, affecting one in every 150 children and their families. Unfortunately, there is little understanding of the causes of ASD, and, despite their broad societal impact, many people believe that the overall research program for autism is incomplete, particularly as it relates to the role of environmental factors. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders, in response to a request from the U.S. Secretary of Health and Human Services, hosted a workshop called "Autism and the Environment: Challenges and Opportunities for Research." The focus was on improving the understanding of the ways in which environmental factors such as chemicals, infectious agents, or physiological or psychological stress can affect the development of the brain. Autism and the Environment documents the concerted effort which brought together the key public and private stakeholders to discuss potential ways to improve the understanding of the ways that environmental factors may affect ASD. The presentations and discussions from the workshop that are described in this book identify a number of promising directions for research on the possible role of different environmental agents in the etiology of autism.
Autism spectrum disorders are developmental disorders. Individuals with autism spectrum disorders develop differently. These differences are usually present in social interaction, communication, and sensory processing, and become visible through a wide variety of behavioral responses that differ from individuals without autism spectrum disorders. Despite significant research efforts, the exact causes of autism spectrum disorders remain poorly understood; however, researchers have gained extensive insights into possible pathomechanisms, even at the molecular level of cells. Many diagnostic criteria have been developed, adapted, and improved. The eight chapters in this book highlight the current state-of-the-art in many areas of autism spectrum disorders. Chapter 1 provides an overview of the epidemiology of autism spectrum disorders and the current knowledge of the underlying pathogenic mechanisms. Chapter 2 summarizes the diagnostic criteria and procedures and highlights present and upcoming therapeutic strategies. Chapter 3 reviews the adverse events and trauma in people with autism spectrum disorders. Chapters 4 and 5 focus on atypical sensory processing, and Chapter 6 discusses the genetic overlap of autism spectrum disorders with other neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD), depression, and schizophrenia. Chapter 7 focuses on the contribution of abnormalities in mitochondria, and chapter 8 discusses gut-brain interactions and a potential role for microbiota in autism spectrum disorders. This book is aimed primarily at clinicians and scientists, but many areas will also be of interest to the layperson.
This book starts with a new sub category of Autism Criminal Autistic Psychopathy and school shootings. It focuses on a number of interventions, including speech and language pathology, speech and language assessment instruments, occupational therapy, improving functional language development in autism with natural gestures, communication boards etc as well as helping people with autism using the pictorial support, training of concepts of significant others, theory of mind, social concepts and a conceptual model for empowering families of children with autism cross culturally. It also examines the issue of hyperandrogenism and evidence-based treatments of autism. In terms of assessment, it focuses on psychological and biological assessment including neurotransmitters systems, structural and functional brain imaging, coping strategies of parents, examines the intertwining of language impairment, specific language impairment and ASD, as well as implicit and spontaneous Theory of Mind reading in ASD. In terms of aetiology, it focuses on genetic factors, epigenetics, synaptic vesicles, toxicity during neurodevelopment, immune system and sex differences. It also examines the link between social cognitive anatomical and neurophysiologic biomarkers and candidate genes. This book will be relevant to all mental health professionals because autism occurs in all the different areas of psychiatry and professionals who will find it helpful will be psychiatrists, psychologists, social workers, nurses, teachers and all those working with persons with Autism including parents who nowadays are interested in knowing more and more, at a detailed level about their children or adults with autism.
Author : Institute of Medicine Publisher : National Academies Press Page : 636 pages File Size : 19,85 MB Release : 1994-01-01 Category : Medical ISBN : 0309049393
The understanding of how to reduce risk factors for mental disorders has expanded remarkably as a result of recent scientific advances. This study, mandated by Congress, reviews those advances in the context of current research and provides a targeted definition of prevention and a conceptual framework that emphasizes risk reduction. Highlighting opportunities for and barriers to interventions, the book draws on successful models for the prevention of cardiovascular disease, injuries, and smoking. In addition, it reviews the risk factors associated with Alzheimer's disease, schizophrenia, alcohol abuse and dependence, depressive disorders, and conduct disorders and evaluates current illustrative prevention programs. The models and examination provide a framework for the design, application, and evaluation of interventions intended to prevent mental disorders and the transfer of knowledge about prevention from research to clinical practice. The book presents a focused research agenda, with recommendations on how to develop effective intervention programs, create a cadre of prevention researchers, and improve coordination among federal agencies.
The second edition of Neurobiology of Disease includes nearly 200 articles surveying all major disorders of the nervous system in both adults and children, focusing on relevant diagnosis and treatments from the perspective of cutting edge clinical and basic neurobiological research. Akin to an encyclopedia of every neurologic disorder, this comprehensive work is ideal for graduate and medical school students, residents, and candidates preparing for their board certification examinations. Each chapter is illustrated with detailed figures, supplemented with descriptive and diagnostic tables, and thoroughly referenced for further investigations. The book's editors, Michael V. Johnston, Harold P. Adams Jr., and Ali Fatemi bring their unique expertise in clinical and research neurology to the overall scope of this work. To further enhance the scope and quality of this new edition, the following Section Editors provided oversight of their respective sections: · Movement Disorders-Joel Perlmutter, Washington University · Dementias-David Knopman, Mayo Clinic · Motorneuron Diseases-Merit Cudkowicz, Massachusetts General Hospital · Paroxysmal Disorders-Solomon Moshe, Albert Einstein College of Medicine · Pediatric Neurology and Developmental Disorders-Tanjala Gipson and Deepa Menon, Kennedy Krieger Institute and Johns Hopkins University · Neuroimmunological Diseases-Carlos Pardo-Villamizar, Johns Hopkins University · Cerebrovascular Diseases-Harold P. Adams Jr., University of Iowa · Peripheral and Autonomic Nervous System Disorders and Pain-Nicholas Maragakis, Johns Hopkins University · Neoplastic and Paraneoplastic Diseases-Lisa DeAngelis, Memorial Sloan-Kettering Cancer Center · Infectious Diseases of the Nervous System-Karen L. Roos, Indiana University · Sleep Disturbances-Mark Dyken, University of Iowa · Substance Abuse and Toxicology Disorders-Barry E. Kosofsky, Weill-Cornell University Medical Center · Neurologic Manifestations of Medical Disorders-John C. Probasco, Johns Hopkins University
The book focuses on implications of traditional and processed foods for autism spectrum disorder (ASD) intervention and management. Numerous phytonutrients and pharmacologically active compounds in edible natural products and diet could influence and offer protection to neuronal dysfunction that occurs due to ASD. The neuroprotective effects of various fruits, vegetables, nuts and seeds phytochemicals, and other natural bioactive ingredients against ASD and related conditions are discussed. Topics such as the possible neuroprotective mechanism of action of these foods and the therapeutic role of antioxidants in relation to ASD are addressed. This book also highlights the scope of using anti-inflammatory agents and antioxidants to promote neurogenesis and improve other symptoms in ASD. It emphasizes personalized nutritional approaches with dietary management of neurodevelopmental disorders/ASD cases. Information in this book is relevant to researchers in the field of complementary and alternative medicine, nutraceuticals, neuroscience, agriculture, nutrition, and food science. This volume is beneficial to students of varying levels, and across multiple disciplines.