ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Long-term memory deficits are associated with elevated synaptic ERK1/2 activation and reversed by mGluR5 antagonism in an animal model of autism.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
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- Severe Neurodevelopmental Disorder in Autosomal Recessive Spinocerebellar Ataxia 13 (SCAR13) Caused by Two Novel Frameshift Variants in GRM1.Cerebellum (London, England) · 2024Article
- Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets.Molecular neurobiology · 2024Review
- Article
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning.Molecular psychiatry · 2023Article
- Treatment-Resistant Epilepsy and Tuberous Sclerosis Complex: Treatment, Maintenance, and Future Directions.Neuropsychiatric disease and treatment · 2023Review
- Altered Expression andCurrent neuropharmacology · 2022Article
- Group 1 Metabotropic Glutamate Receptors in Neurological and Psychiatric Diseases: Mechanisms and Prospective.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism.Psychopharmacology · 2022Article
- Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction.Molecular psychiatry · 2022Article
- Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex.International journal of molecular sciences · 2021Article
- MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes.International journal of molecular sciences · 2020Review
- A TrkB agonist and ampakine rescue synaptic plasticity and multiple forms of memory in a mouse model of intellectual disability.Neurobiology of disease · 2020Article
- Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities.Translational psychiatry · 2019Article
- Hypothesis-driven investigations of diverse pharmacological targets in two mouse models of autism.Autism research : official journal of the International Society for Autism Research · 2019Article
- Molecular Mechanisms of Synaptic Dysregulation in Fragile X Syndrome and Autism Spectrum Disorders.Frontiers in molecular neuroscience · 2019Review
- The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice.Scientific reports · 2018Article
- mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.Psychopharmacology · 2018Article
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4 authors.
Funding
Abstract
A significant proportion of patients with autism exhibit some degree of intellectual disability. The BTBR T(+) Itpr3(tf)/J mouse strain exhibits behaviors that align with the major diagnostic criteria of autism. To further evaluate the BTBR strain's cognitive impairments, we quantified hippocampus-dependent object location memory (OLM) and found that one-third of the BTBR mice exhibited robust memory, whereas the remainder did not. Fluorescence deconvolution tomography was used to test whether synaptic levels of activated extracellular signal-regulated kinase 1/2 (ERK1/2), a protein that contributes importantly to plasticity, correlate with OLM scores in individual mice. In hippocampal field CA1, the BTBRs had fewer post-synaptic densities associated with high levels of phosphorylated (p-) ERK1/2 as compared with C57BL/6 mice. Although counts of p-ERK1/2 immunoreactive synapses did not correlate with OLM performance, the intensity of synaptic p-ERK1/2 immunolabeling was negatively correlated with OLM scores across BTBRs. Metabotropic glutamate receptor (mGluR) 5 signaling activates ERK1/2. Therefore, we tested whether treatment with the mGluR5 antagonist MPEP normalizes synaptic and learning measures in BTBR mice: MPEP facilitated OLM and decreased synaptic p-ERK1/2 immunolabeling intensity without affecting numbers of p-ERK1/2+ synapses. In contrast, semi-chronic ampakine treatment, which facilitates memory in other models of cognitive impairment, had no effect on OLM in BTBRs. These results suggest that intellectual disabilities associated with different neurodevelopmental disorders on the autism spectrum require distinct therapeutic strategies based on underlying synaptic pathology.
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