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Mechanisms Of Synaptic Development And Premature Aging In Drosophila: A Dissertation, Yihang Li 2016 University of Massachusetts Medical School

Mechanisms Of Synaptic Development And Premature Aging In Drosophila: A Dissertation, Yihang Li

GSBS Dissertations and Theses

Development and aging, two fundamental aspects of life, remain key biological processes that researchers try to understand. Drosophila melanogaster, thanks to its various merits, serves as an excellent model to study both of these processes. This thesis includes two parts. In the first part, I discuss our finding that the presynaptic neuron controls a retrograde signaling pathway by releasing essential components via exosomes. During synaptic development, postsynaptic cells send retrograde signals to adjust the activity and growth of presynaptic cells. It remains unclear what the mechanism is which triggers the release of retrograde signals; and how presynaptic cells are involved ...


Dyslexia And Language Impairment Associated Genetic Markers Influence Cortical Thickness And White Matter In Typically Developing Children, John D. Eicher, Jean A. Frazier, David N. Kennedy, Jeffrey R. Gruen 2016 Yale University

Dyslexia And Language Impairment Associated Genetic Markers Influence Cortical Thickness And White Matter In Typically Developing Children, John D. Eicher, Jean A. Frazier, David N. Kennedy, Jeffrey R. Gruen

Jean A. Frazier

Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by ...


Impaired Neurodevelopment By The Low Complexity Domain Of Cpeb4 Reveals A Convergent Pathway With Neurodegeneration, Jihae Shin, Johnny S. Salameh, Joel D. Richter 2016 University of Massachusetts Medical School

Impaired Neurodevelopment By The Low Complexity Domain Of Cpeb4 Reveals A Convergent Pathway With Neurodegeneration, Jihae Shin, Johnny S. Salameh, Joel D. Richter

Open Access Articles

CPEB4 is an RNA binding protein expressed in neuronal tissues including brain and spinal cord. CPEB4 has two domains: one that is structured for RNA binding and one that is unstructured and low complexity that has no known function. Unstructured low complexity domains (LCDs) in proteins are often found in RNA-binding proteins and have been implicated in motor neuron degenerative diseases such as amyotrophic lateral sclerosis, indicating that these regions mediate normal RNA processing as well as pathological events. While CPEB4 null knockout mice are normal, animals expressing only the CPEB4 LCD are neonatal lethal with impaired mobility that display ...


The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, Michele Barry 2016 Seton Hall University

The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, Michele Barry

Seton Hall University Dissertations and Theses (ETDs)

The inability to remember events experienced very early in life is referred to as Infantile Amnesia (IA) and has been observed in both humans and animals. Over the years interest in the phenomenon waned, but has recently increased with the discovery of new neurobiological methods to study brain function (e.g., Callaghan, Li & Richardson, 2014). The neurobiological mechanism behind IA has yet to be determined, but several innovative theories have been developed with these new research methods. The neurogenesis hypothesis theorizes that increased neurogenesis during early development disrupts previously established memories. The hippocampus, an area that mediates both the memory ...


Prenatal Exposure To Social Stress Alters Adult Behavior In Syrian Hamsters, Genna Jones 2016 Neuroscience

Prenatal Exposure To Social Stress Alters Adult Behavior In Syrian Hamsters, Genna Jones

Georgia State Undergraduate Research Conference

No abstract provided.


Dyslexia And Language Impairment Associated Genetic Markers Influence Cortical Thickness And White Matter In Typically Developing Children, John D. Eicher, Jean A. Frazier, David N. Kennedy, Jeffrey R. Gruen, Pediatric Imaging Neurocognition Genetics Study 2016 Yale University

Dyslexia And Language Impairment Associated Genetic Markers Influence Cortical Thickness And White Matter In Typically Developing Children, John D. Eicher, Jean A. Frazier, David N. Kennedy, Jeffrey R. Gruen, Pediatric Imaging Neurocognition Genetics Study

University of Massachusetts Medical School Faculty Publications

Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by ...


Roles Of Planar Cell Polarity Proteins In Copa Axon Pathfinding, Ashley Morgan Purdy 2016 Virginia Commonwealth University

Roles Of Planar Cell Polarity Proteins In Copa Axon Pathfinding, Ashley Morgan Purdy

Theses and Dissertations

In zebrafish, CoPA (Commissural Primary Ascending) is the first among ascending commissural axons to pathfind anteriorly and form the spinal commissure. One pathway that guides their anterior growth is the planar cell polarity (PCP) signaling pathway, but it is not fully known how PCP signaling regulates anterior guidance. We examined CoPA pathfinding in various PCP mutants to determine if anterior-posterior (A-P) guidance of CoPAs is dependent on PCP signaling. We found that certain PCP mutants exhibited anterior pathfinding defects, with approximately half of all affected CoPAs migrating incorrectly posteriorly. By using a translation-blocking DCC (Deleted in Colorectal ...


Early Neurodevelopment: Notch Signaling, Axial Differentiation, Brain Patterning, And Neurogenesis, Adrian M. Bebenek '17 2016 Illinois Mathematics and Science Academy

Early Neurodevelopment: Notch Signaling, Axial Differentiation, Brain Patterning, And Neurogenesis, Adrian M. Bebenek '17

Independent Study

The vastly complex, delicate nature of the nervous system calls for a highly effective development system. The development of the nervous system begins early in embryogenesis and is one of the last systems to be completed after birth. Deemed to be one of the most important steps in the evolutionary progression towards sophisticated life, the pathways regulating neurodevelopment are highly specialized and conserved. Embryonic neurodevelopment is an important starting point for the understanding of brain anatomy, function, and its neurobiology. The past few decades have brought about numerous technological advancements allowing for the study of the earliest stages of embryonic ...


Alignment Of Neurochemically Defined Modules In Multimodal Aspects Of The Mouse Inferior Colliculus., Chris H. Dillingham 2016 James Madison University

Alignment Of Neurochemically Defined Modules In Multimodal Aspects Of The Mouse Inferior Colliculus., Chris H. Dillingham

Senior Honors Projects

Processing of sound requires precise coordination of various levels of the auditory system. Auditory reflexes and orientation behaviors require interactions with other systems and modalities, emphasizing the importance of highly organized integrative circuits. The inferior colliculus (IC) is a unique midbrain structure in that it exhibits aspects that are specifically arranged for processing auditory cues, as well as regions that handle multisensory inputs and thereby exhibit an entirely different organization. While the central nucleus of the IC (CNIC) is primarily auditory and arranged tonotopically, the lateral cortex (LCIC) is multimodal and exhibits a unique array of modular and extramodular fields ...


Potential For Aerobic Exercise To Release Growth Factors To Induce Cognitive Changes In Children With Autism Spectrum Disorder, Maya Harrington 2016 Virginia Commonwealth University

Potential For Aerobic Exercise To Release Growth Factors To Induce Cognitive Changes In Children With Autism Spectrum Disorder, Maya Harrington

Undergraduate Research Posters

Autism Spectrum Disorder (ASD) is becoming increasingly prevalent among adolescents, and while the number of individuals diagnosed with the disorder grows, there continues to be no cure or even a clear treatment path for ASD. This study analyzes the biological stimulations that create cognitive changes—which are induced by intensive aerobic exercise—within the brains of individuals ages 8-18 diagnosed with autism. I studied journal articles on the current treatments available for ASD, the increasing prevalence of the disease, the cognitive alterations of the autistic brain relative to the brains of individuals without the disease, the release of growth factors ...


Exercise During The Juvenile Period Produces Long Lasting Stress Protection Potentially Subserved By Epigenetic Alterations To The Serotonergic System, Nicole L. Rumian 2016 University of Colorado, Boulder

Exercise During The Juvenile Period Produces Long Lasting Stress Protection Potentially Subserved By Epigenetic Alterations To The Serotonergic System, Nicole L. Rumian

Undergraduate Honors Theses

Exercise is capable of producing a myriad of beneficial alterations in brain chemistry and function which can help prevent stress-related psychiatric disorders, such as anxiety and depression. Recent work from our lab demonstrates that 6 weeks of exercise initiated in early life produces lasting protection against stress-induced anxiety and depressive like behaviors, whereas, in adults, this protection is transient and dissipates upon cessation of exercise. Thus, when exercise begins at a young age, the neurobiological improvements remain intact even after exercise has ceased for a period of time. The mechanism underlying this long lasting protection is currently unknown. Furthermore, it ...


Using Spiral Dynamic Theory For Adult Civic Engagement Research And Social Justice Education, Lisa R. Brown 2016 University of Georgia

Using Spiral Dynamic Theory For Adult Civic Engagement Research And Social Justice Education, Lisa R. Brown

Adult Education Research Conference

Empirical civic engagement research based in a South American context. Participants included adult learner populations engaged in revolutionary protests that opposed private for-profit education in Chile. Findings were higher order Spiral Dynamic Theory thinking at the for-profits and lower civic engagement.


Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson 2015 University of Nebraska Medical Center

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until ...


Rna Sequence Analysis Of Human Huntington Disease Brain Reveals An Extensive Increase In Inflammatory And Developmental Gene Expression, Adam Labadorf, Andrew Hoss, Valentina Lagomarsino, Jeanne C. Latourelle, Tiffany C. Hadzi, Joli Bregu, Marcy E. MacDonald, James F. Gusella, Jiang-Fan Chen, Schahram Akbarian, Zhiping Weng, Richard H. Myers 2015 Boston University School of Medicine

Rna Sequence Analysis Of Human Huntington Disease Brain Reveals An Extensive Increase In Inflammatory And Developmental Gene Expression, Adam Labadorf, Andrew Hoss, Valentina Lagomarsino, Jeanne C. Latourelle, Tiffany C. Hadzi, Joli Bregu, Marcy E. Macdonald, James F. Gusella, Jiang-Fan Chen, Schahram Akbarian, Zhiping Weng, Richard H. Myers

Open Access Articles

Huntington's Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR < 0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.


Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber 2015 The University of Western Ontario

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse ...


Relation Of Childhood Home Environment To Cortical Thickness In Late Adolescence: Specificity Of Experience And Timing, Brian B. Avants, Daniel A Hackman, Laura Betancourt, Gwendolyn M. Lawson, Hallam Hurt, Martha J. Farah 2015 University of Pennsylvania

Relation Of Childhood Home Environment To Cortical Thickness In Late Adolescence: Specificity Of Experience And Timing, Brian B. Avants, Daniel A Hackman, Laura Betancourt, Gwendolyn M. Lawson, Hallam Hurt, Martha J. Farah

Neuroethics Publications

What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of ...


An Emerging Role For Prdm Family Genes In Dorsoventral Patterning Of The Vertebrate Nervous System, Denise A. Zannino, Charles G. Sagerstrom 2015 University of Massachusetts Medical School

An Emerging Role For Prdm Family Genes In Dorsoventral Patterning Of The Vertebrate Nervous System, Denise A. Zannino, Charles G. Sagerstrom

Open Access Articles

The embryonic vertebrate neural tube is divided along its dorsoventral (DV) axis into eleven molecularly discrete progenitor domains. Each of these domains gives rise to distinct neuronal cell types; the ventral-most six domains contribute to motor circuits, while the five dorsal domains contribute to sensory circuits. Following the initial neurogenesis step, these domains also generate glial cell types-either astrocytes or oligodendrocytes. This DV pattern is initiated by two morphogens-Sonic Hedgehog released from notochord and floor plate and Bone Morphogenetic Protein produced in the roof plate-that act in concentration gradients to induce expression of genes along the DV axis. Subsequently, these ...


Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang 2015 Cincinnati Children's Hospital Research Foundation

Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang

Victor R. Ambros

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously ...


Play As The Foundation Of Human Intelligence: The Illuminating Role Of Human Brain Evolution And Development And Implications For Education And Child Development., Aaron P. Blaisdell 2015 University of California, Los Angeles

Play As The Foundation Of Human Intelligence: The Illuminating Role Of Human Brain Evolution And Development And Implications For Education And Child Development., Aaron P. Blaisdell

Journal of Evolution and Health

Children love to play. Why do they find such a frivolous activity so pleasurable and desirable? Perhaps it is not frivolous, but instead is an adaptation designed to guide proper cognitive development in human children. To understand why, I marshal evidence from different fields to build a case for play as a central behavioral mechanism of human brain and cognitive development. I start with a discussion of human evolution, focusing on the evolution of human physiology, tool-use, the human brain, and life-history strategy, and development, and how these are all connected as an adaptive suite. The anthropological and developmental evidence ...


Relationships Between Age And White Matter Integrity In Children With Phenylketonuria, Erika M. Wesonga 2015 Washington University in St. Louis

Relationships Between Age And White Matter Integrity In Children With Phenylketonuria, Erika M. Wesonga

Arts & Sciences Electronic Theses and Dissertations

Objective: Phenylketonuria (PKU) is a hereditary metabolic disorder associated with cognitive compromise. Diffusion tensor imaging (DTI) has allowed detection of poorer microstructural white matter integrity in children with PKU, with decreased mean diffusivity (MD) in comparison with healthy children. However, very little research has been conducted to examine the trajectory of white matter development in this population. The present study investigated potential differences in the developmental trajectory of MD between children with early- and continuously-treated PKU and healthy children across a range of brain regions.

Methods: Children with PKU (n = 31, mean age = 12.2 years) were recruited through metabolic ...


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