The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition PDF Download

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The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition PDF Author: Caren L. August
Publisher:
ISBN:
Category : Autism spectrum disorders
Languages : en
Pages : 51

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Book Description
Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition

The Effect of Prenatal Valproate Exposure in Serotonin Transporter Knockout Rats On Anxiety and Cognition PDF Author: Caren L. August
Publisher:
ISBN:
Category : Autism spectrum disorders
Languages : en
Pages : 51

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Book Description
Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.

Deciphering serotonin´s role in neurodevelopment

Deciphering serotonin´s role in neurodevelopment PDF Author: Dirk Schubert
Publisher: Frontiers E-books
ISBN: 2889192768
Category : Neurosciences. Biological psychiatry. Neuropsychiatry
Languages : en
Pages : 132

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Book Description
One of the most challenging questions in neurobiology to tackle is how the serotonergic system steers neurodevelopment. With the increase in serotonergic anxiolytic and antidepressant drugs, serotonin was thought to signal adversity or to serve as an emotional signal. However, a vast amount of literature is accumulating showing that serotonin rather mediates neuroplasticity and plays a key role in early developmental processes. For instance, selective serotonin reuptake inhibitors (SSRIs), serving as antidepressants, increase neurogenesis and trigger autism-related brain and behavioural changes during embryonic and perinatal exposure. Moreover, serotonin transporter gene variation is associated with alterations in corticolimbic neuroplasticity, autism-related neuroanatomical changes, as well alterations in social behaviour. Hence, the view is emerging that early life changes in serotonin levels influence the developmental course of socio-emotional brain circuits that are relevant for autism and other neurodevelopmental disorders. It is particularly exciting that the effects of embryonic and perinatal SSRI exposure and serotonin transporter gene variation on neurodevelopment seem to overlap to a large extent, at the cellular as well as the behavioural level. Yet, the precise mechanisms by which serotonin mediates neurodevelopment in the normal and ´autistic´ brain is unclear. Whereas serotonin has a placental origin during early gestation, serotonergic neurons develop during midgestation under the control of a cascade of transcription factors determining the fate of mid-hindbrain neurons that together for the Raphe nuclei. These neurons are among the earliest neurons to be generated, and because serotonin is released before any conventional synapses are formed, serotonin is suspected to influence crucial neurodevelopmental processes such as proliferation,migration and network formation. During late gestation they target their final destinations in, for instance, the cortex, where they affect the secretion of reelin. Reelin is a secreted extracellular matrix glycoprotein that helps to regulate processes of neuronal migration and positioning in the developing cortex by controlling cell–cell interactions. During the late prenatal and early postnatal phase (in rodents) serotonin further shapes the outgrowth of projecting neurons, synaptic connectivity, and the morphology of white fiber tracts. This is under the influence of transient serotonin transporter expression in (thalamo)cortical projections, sensory and prefrontal cortices and the hippocampus, as well as the local expression patterns of 5-HT1A, 5-HT1B and 5-HT3A receptors that each exert their specific roles in neuronal migration, remodeling of axons, and controlling dendritic complexity. There is also evidence that serotonin influences neural activity in locus ceroeleus neurons. Hence, serotonin appears to influence the development of both short- and long-distance connections in the brain. This Research Topic is devoted to studies pinpointing the neurodevelopmental effects of serotonin in relation to prenatal SSRI exposure, serotonin transporter gene variation, and autism/neurodevelopmental disorders, using a wide-variety of cellular and molecular neurobiological techniques like, (epi)genetics, knockout, knockdown, neuroanatomy, physiology, MRI and behaviour in rodents and humans. We especially encouraged attempts to cross-link the neurodevelopmental processes across the fields of prenatal SSRI exposure, serotonin transporter gene variation, and autism/neurodevelopmental disorders, as well as new views on the positive or beneficial effects on serotonin-mediated neurodevelopmental changes.

Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability

Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability PDF Author: Carlo Sala
Publisher: Academic Press
ISBN: 0128005335
Category : Medical
Languages : en
Pages : 394

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Book Description
Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability provides the latest information on Autism spectrum disorders (ASDs), the lifelong neurodevelopmental disorders that present in early childhood and affect how individuals communicate and relate to others and their surroundings. In addition, three quarters of ASD patients also manifest severe intellectual disability. Though certain genes have been implicated, ASDs remain largely a mystery, and research looking into causes and cellular deficits are crucial for better understanding of neurodevelopmental disorders. Despite the prevalence and insidious nature of this disorder, this book remains to be an extensive resource of information and background on the state of current research in the field. The book serves as a reference for this purpose, and discusses the crucial role synaptic activity plays in proper brain function. In addition, the volume discusses the neurodevelopmental synaptopathies and serves as a resource for scientists and clinicians in all biomedical science specialties. This research has been crucial for recent studies that have provided a rationale for the development of pharmacological agents able to counteract functional synaptic anomalies and potentially ameliorate some ASD symptoms. Introduces the genetic and non-genetic causes of autism and associated intellectual disabilities Describes the genes implicated in autistic spectrum disorders and their function Considers major individual genetic causes of autism, Rett syndrome, Fragile X syndrome, and other autism spectrum disorders, as well as their classification as synaptopathies Presents a thorough discussion of the clinical aspects of multiple neurodevelopmental disorders and the experimental models that exist to study their pathophysiology in vitro and in vivo, including animal models and patient-derived stem cell culture