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E-raamat: Genetic Models and Molecular Pathways Underlying Autism Spectrum Disorders

Volume editor (Director, Indiana Clinical and Translational Sciences Institute, Distingushed Professor and Executive Associate Dean for Research Affairs, Indiana University School of Medicine)
  • Formaat: PDF+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 14-Nov-2018
  • Kirjastus: Academic Press Inc.(London) Ltd
  • Keel: eng
  • ISBN-13: 9780444641953
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Genetic Models and Molecular Pathways Underlying Autism Spectrum DisordersSuurem pilt
  • Formaat: PDF+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 14-Nov-2018
  • Kirjastus: Academic Press Inc.(London) Ltd
  • Keel: eng
  • ISBN-13: 9780444641953
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Genetic Models and Molecular Pathways Underlying Autism Spectrum Disorders, Volume 241 provides the most recent information on the animal model systems that are available to study different forms of autism spectrum disorders. In addition to genetically engineered animals that uniquely model genetic forms of ASD, this volume also provides detailed chapters on a variety of specific topics, including An overview of genetic models of ASDs, Phenotypic modeling of ASD symptoms, Molecular mechanisms of NF1 model of ASD symptoms, Ube3a gene dosage disorders: molecular and circuit mechanisms of ASD, Circuit dysfunctions in ASD models, ERK signaling in genetic models of ASD, and more.

  • Presents a timely, comprehensive assessment of the field
  • Includes helpful summaries on current knowledge, gaps and future directions in autism research
Contributors v
Preface xi
Chapter 1 Overview of Genetic Models of Autism Spectrum Disorders
1(36)
Jheel Patel
Jodi L. Lukkes
Anantha Shekhar
1 Introduction
2(4)
2 Theories of ASD Development
6(6)
2.1 Neuronal Number and Growth
6(1)
2.2 Dendritic Morphogenesis
7(2)
2.3 Excitation-Inhibition Imbalance
9(1)
2.4 Neuroinflammation
9(1)
2.5 Environmental Factors
10(2)
3 Mechanisms of ASD Development
12(7)
3.1 Disruptions in Synaptic Transmission
12(4)
3.2 Disruptions in Intracellular Kinase Signaling Pathways
16(3)
4 Limitations and Challenges of Genetic Animal Models
19(3)
5 Future of Genetic Models
22(3)
5.1 Genome Editing
22(1)
5.2 Modulation of Neuronal Activity
23(1)
5.3 Biological Network Studies
24(1)
5.4 Stem Cell Approaches
24(1)
5.5 Gut Microbiome Connection
24(1)
6 Conclusions
25(12)
Acknowledgments
26(1)
References
26(11)
Chapter 2 Neurofibromatosis Type 1 as a Model System to Study Molecular Mechanisms of Autism Spectrum Disorder Symptoms
37(26)
Andrei I. Molosh
Anantha Shekhar
1 Introduction
38(1)
2 Background
38(1)
3 Cognitive and Behavioral Problems in Patients With NF1
39(1)
4 NF1 Genetically Engineered Mouse as Model Systems
40(2)
5 The Role of Neurofibromin in Modulation of Ras/ERK, PI3K/mTOR and cAMP Intracellular Pathways
42(4)
6 Amelioration of Cognitive Problems in Mice and Humans Using Different Pharmacological Tools
46(6)
6.1 MEK Inhibitors
46(1)
6.2 Pak1 Inhibitors
47(2)
6.3 Statins
49(1)
6.4 GABA Inhibitors
50(1)
6.5 Other Therapeutic Candidates
51(1)
7 Concluding Remarks and Perspectives
52(11)
Acknowledgment
53(1)
References
53(10)
Chapter 3 ERK/MAPK Signaling and Autism Spectrum Disorders
63(50)
Joseph Vithayathil
Joanna Pucilowska
Gary E. Landreth
1 Introduction
63(1)
2 ERK/MAPK Pathway and Autism
64(2)
3 Discovery of MAPK/ERK Signaling
66(2)
4 MAPK Pathway Activation
68(2)
5 ERK/MAPK Pathway Regulation
70(3)
6 Developmental Roles for ERK Signaling
73(2)
7 ERK/MAPK Signaling and Synaptic Plasticity
75(6)
7.1 ERK Signaling at the Synapse
79(1)
7.2 Local Translation
79(1)
7.3 ERK Signaling in the Nucleus
80(1)
8 The Role of ERK/MAPK Signaling in Behavior
81(2)
8.1 Spatial Memory
81(1)
8.2 Associative Learning
81(1)
8.3 Reward/Addiction Behaviors
82(1)
8.4 Social Behaviors
82(1)
9 ERK Signaling in Rasopathies and ASD Models
83(3)
9.1 Neurofibromatosis Type 1
83(1)
9.2 Noonan Syndrome
84(1)
9.3 Costello Syndrome
85(1)
9.4 Cardio-Facio-Cutaneous Syndrome
86(1)
10 Mutations of ERK-Pathway Related Signaling Proteins and ASD
86(5)
10.1 SynGAP1
86(1)
10.2 FMR1
87(2)
10.3 16p11.2 Deletion/Duplication
89(1)
10.4 DiGeorge Syndrome (22q11 Deletion Syndrome)
90(1)
10.5 Rett Syndrome and Tuberous Sclerosis
90(1)
10.6 BTBR Inbred Mouse Strain
91(1)
11 Conclusion
91(22)
References
92(21)
Chapter 4 From Bedside to Bench and Back: Translating ASD Models
113(46)
Hayley P. Drozd
Sotirios F. Karathanasis
Andrei I. Molosh
Jodi L. Lukkes
D. Wade Clapp
Anantha Shekhar
1 Introduction
114(1)
2 Optimizing Clinical Concepts of ASD---"The Bedside Efforts"
115(9)
2.1 Genetic Biomarkers
119(1)
2.2 Imaging Biomarkers
120(1)
2.3 Serum Biomarkers
121(1)
2.4 Multimodal Analysis
122(2)
3 Optimizing the Preclinical Model---"The Bench Efforts"
124(4)
4 Translating to Therapies---"Back to the Bedside"
128(9)
4.1 Bench-to-Bedside Pharmacotherapy
128(6)
4.2 Bedside-to-Bedside Pharmacotherapy
134(2)
4.3 Measuring Outcomes in Pharmacotherapy
136(1)
5 Conclusions
137(22)
Acknowledgments
137(1)
References
137(22)
Chapter 5 Studying Child Development in Genetic Models of ASD
159(34)
Shruti Garg
Jonathan Green
1 Phenotype and Genotype in ASD
160(2)
2 Monogenic Syndromic ASD and the Comparative Method
162(1)
3 The ASD Behavioral Phenotype Across Genetic Models of ASD
163(4)
3.1 Summary
167(1)
4 Developmental Trajectory of ASD Across Genetic Syndromes
167(6)
4.1 Structural and Functional Brain Abnormalities
168(2)
4.2 Neurocognitive Markers
170(1)
4.3 Motor Function
171(1)
4.4 Behavior Development
172(1)
4.5 Summary
172(1)
5 Experimental Intervention
173(7)
5.1 Fragile X Disorder (FXS): GABA-Glutamate Balance
174(3)
5.2 NF1: The MAPK/ERK Cell Signaling Pathway
177(2)
5.3 TSC: The mTOR Pathway
179(1)
5.4 Rett and Phelan-McDermid Syndromes: Growth and Neurotrophic Factors
179(1)
6 Summary
180(13)
References
182(11)
Chapter 6 Measurement Considerations in Pediatric Research on Autism Spectrum Disorders
193
Karin S. Walsh
Srishti Rau
1 Introduction
193(1)
2 Prevalence
194(2)
2.1 In the General Population
194(1)
2.2 In Genetic Syndromes
195(1)
3 Diagnostic Guidelines
196(2)
3.1 Level 1---Screening
196(1)
3.2 Level 2: Comprehensive Evaluation
197(1)
4 Assessing ASD Symptomatology
198(2)
4.1 Parent Report
198(1)
4.2 Diagnostic Observation
199(1)
5 Intellectual and Adaptive Assessment
200(2)
6 Language Assessment
202(1)
7 Psychiatric Comorbidities
203(4)
7.1 Sleep
203(1)
7.2 Attention-Deficit/Hyperactivity Disorder
204(1)
7.3 Anxiety
204(1)
7.4 Obsessive Compulsive Disorder
205(1)
7.5 Depression
205(1)
7.6 Bipolar Disorder
206(1)
7.7 Externalizing Disorders
206(1)
8 NF1 as a Model for Examining ASD in Genetic Syndromes
207(2)
9 Conclusions
209
References
209
Anantha Shekhar, MD, PhD, is a distinguished professor of psychiatry, neurobiology and pharmacology at Indiana University and holds the August M. Watanabe Chair of Medical Research, Professor of Psychiatry. He has been continuously funded by the National Institutes of Health for his basic, clinical and translational research since 1989. Dr. Shekhar leads a successful basic and clinical research programs in the areas of stress, anxiety and neuropsychiatric disorders. A number of grants from the National Institutes of Health, private foundations, and commercial collaborations currently support his research. He has authored over 200 peer reviewed publications. He has received several university and national awards and has been a member and chair of several NIH study sections. He has also served as a member of the Board of Scientific Advisors for the National Institute of Mental Health. He has served as the president of the Society of Clinical and Translational Sciences and the president of the Association for Clinical and Translational Sciences. He currently serves as a member of the Advisory Council for National Center for Advancing Translation Sciences (NCATS) of the NIH and a member of the Board of Governors for the Cures Acceleration Network (CAN) at the NIH.
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