Fragile X mental retardation protein is required for chemically‐induced long‐term potentiation of the hippocampus in adult mice

Shang, Yuze; Wang, Hansen; Mercaldo, Valentina; Li, Xiangyao; Chen, Tao; Zhuo, Min

doi:10.1111/j.1471-4159.2009.06314.x

Cited by 72Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Fragile X mental retardation protein is required for chemically‐induced long‐term potentiation of the hippocampus in adult mice

Shang, Yuze, Wang, Hansen, Mercaldo, Valentina, Li, Xiangyao, Chen, Tao, Zhuo, Min·2009·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2009.06314.x

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Abstract

Fragile X syndrome (FXS), a common form of inherited mental retardation, is caused by the lack of fragile X mental retardation protein (FMRP). The animal model of FXS, Fmr1 knockout mice, have deficits in the Morris water maze and trace fear memory tests, showing impairment in hippocampus‐dependent learning and memory. However, results for synaptic long‐term potentiation (LTP), a key cellular model for learning and memory, remain inconclusive in the hippocampus of Fmr1 knockout mice. Here, we demonstrate that FMRP is required for glycine induced LTP (Gly‐LTP) in the CA1 of hippocampus. This form of LTP requires activation of post‐synaptic NMDA receptors and metabotropic glutamateric receptors, as well as the subsequent activation of extracellular signal‐regulated kinase (ERK) 1/2. However, paired‐pulse facilitation was not affected by glycine treatment. Genetic deletion of FMRP interrupted the phosphorylation of ERK1/2, suggesting the possible role of FMRP in the regulation of the activity of ERK1/2. Our study provide strong evidences that FMRP participates in Gly‐LTP in the hippocampus by regulating the phosphorylation of ERK1/2, and that improper regulation of these signaling pathways may contribute to the learning and memory deficits observed in FXS.

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FMRP activity is regulated in response to metabotropic glutamate receptors, AMPA receptors, GABA receptors, NMDA receptors, and TrkB receptors.
“FMRP activity is regulated in response to metabotropic glutamate receptors (mGluRs) (78), 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptors (79), γ-aminobutyric acid (GABA) receptors (76,80,81), N-methyl-d-aspartate (NMDA) receptors (82)(83)(84), and the tyrosine kinase or BDNF/NT-3 growth factor (TrkB) receptors (85).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [81]

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Authors: Shang, Y., Wang, H., Mercaldo, V., Li, X., Chen, T., & Zhuo, M.
Affiliations: University of Toronto (CA)
ORCID: Wang, Hansen
Chen, Tao
Zhuo, Min
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2009-10-12
Volume: 111
Issue: 3
Pages: 635-646
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2009.06314.x
OpenAlex: W2020298925
Cited by: 72
References: 89
Citations by year: 2026: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 7 · 2012: 9
FWCI: 4.46
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Library and Archives Canada (Government of Canada) (submittedVersion)
TSpace (University of Toronto) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: fragile X syndrome, FMRP, long-term potentiation, hippocampus, CA1, NMDA receptor, metabotropic glutamate receptors, ERK1/2 phosphorylation, paired-pulse facilitation, learning and memory impairment, Fmr1 knockout mice
MeSH terms: Alanine, Analysis of Variance, Animals, Biophysics, Bromodeoxyuridine, Butadienes, Electric Stimulation, Enzyme Inhibitors, Gene Expression Regulation, Glycine, Hippocampus, Male, Nitriles, Picrotoxin, 2-Amino-5-phosphonovalerate, Long-Term Potentiation, Pyramidal Cells, Mice, Knockout, Patch-Clamp Techniques, Glycine Agents, Excitatory Amino Acid Antagonists, GABA Antagonists, Mitogen-Activated Protein Kinase Kinases, Mice, Fragile X Messenger Ribonucleoprotein 1, In Vitro Techniques

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Fragile X mental retardation protein is required for chemically‐induced long‐term potentiation of the hippocampus in adult mice

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