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Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors
by
Lee, Yunjin
, Lee, Eun-Hwa
, Kim, Ji-Eun
, Kim, Hannah
, Han, Pyung-Lim
, Park, Jin-Young
, Choi, Juli
, Lee, Jung-Eun
in
Amphetamines
/ Animal models
/ Animals
/ Autism
/ Autistic Disorder - metabolism
/ Autistic Disorder - pathology
/ Behavior, Animal
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Caudate-putamen
/ Cell Biology
/ Corpus Striatum - metabolism
/ Corpus Striatum - pathology
/ Dopamine
/ Dopamine D1 receptors
/ Dopamine D2 receptors
/ Dopamine transporter
/ Extracellular Signal-Regulated MAP Kinases - metabolism
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Neostriatum
/ Neurobiology
/ Neurology
/ Neurosciences
/ Optogenetics
/ Phenotypes
/ Phosphorylation
/ Receptor mechanisms
/ Receptor, Metabotropic Glutamate 5 - metabolism
/ Receptors, Dopamine D1 - metabolism
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Rodents
/ siRNA
/ Social Behavior
/ Substantia nigra
/ Substantia Nigra - metabolism
2018
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Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors
by
Lee, Yunjin
, Lee, Eun-Hwa
, Kim, Ji-Eun
, Kim, Hannah
, Han, Pyung-Lim
, Park, Jin-Young
, Choi, Juli
, Lee, Jung-Eun
in
Amphetamines
/ Animal models
/ Animals
/ Autism
/ Autistic Disorder - metabolism
/ Autistic Disorder - pathology
/ Behavior, Animal
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Caudate-putamen
/ Cell Biology
/ Corpus Striatum - metabolism
/ Corpus Striatum - pathology
/ Dopamine
/ Dopamine D1 receptors
/ Dopamine D2 receptors
/ Dopamine transporter
/ Extracellular Signal-Regulated MAP Kinases - metabolism
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Neostriatum
/ Neurobiology
/ Neurology
/ Neurosciences
/ Optogenetics
/ Phenotypes
/ Phosphorylation
/ Receptor mechanisms
/ Receptor, Metabotropic Glutamate 5 - metabolism
/ Receptors, Dopamine D1 - metabolism
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Rodents
/ siRNA
/ Social Behavior
/ Substantia nigra
/ Substantia Nigra - metabolism
2018
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Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors
by
Lee, Yunjin
, Lee, Eun-Hwa
, Kim, Ji-Eun
, Kim, Hannah
, Han, Pyung-Lim
, Park, Jin-Young
, Choi, Juli
, Lee, Jung-Eun
in
Amphetamines
/ Animal models
/ Animals
/ Autism
/ Autistic Disorder - metabolism
/ Autistic Disorder - pathology
/ Behavior, Animal
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Caudate-putamen
/ Cell Biology
/ Corpus Striatum - metabolism
/ Corpus Striatum - pathology
/ Dopamine
/ Dopamine D1 receptors
/ Dopamine D2 receptors
/ Dopamine transporter
/ Extracellular Signal-Regulated MAP Kinases - metabolism
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Neostriatum
/ Neurobiology
/ Neurology
/ Neurosciences
/ Optogenetics
/ Phenotypes
/ Phosphorylation
/ Receptor mechanisms
/ Receptor, Metabotropic Glutamate 5 - metabolism
/ Receptors, Dopamine D1 - metabolism
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Rodents
/ siRNA
/ Social Behavior
/ Substantia nigra
/ Substantia Nigra - metabolism
2018
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Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors
Journal Article
Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors
2018
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Overview
The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.
Publisher
Springer US,Springer Nature B.V
Subject
/ Animals
/ Autism
/ Autistic Disorder - metabolism
/ Autistic Disorder - pathology
/ Biomedical and Life Sciences
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Corpus Striatum - metabolism
/ Dopamine
/ Extracellular Signal-Regulated MAP Kinases - metabolism
/ Receptor, Metabotropic Glutamate 5 - metabolism
/ Receptors, Dopamine D1 - metabolism
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Rodents
/ siRNA
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