ArticleMolecular brain2015
NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.
Article in Molecular brain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 28 citations in OpenAlex.
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- Reduced TREM2 activation in microglia of patients with Alzheimer's disease.FEBS open bio · 2021Article
- Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene.Genes, brain, and behavior · 2020Article
- The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents.International journal of molecular sciences · 2019Review
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- DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex.Epigenetics & chromatin · 2018Article
- Transethnic genome-wide scan identifies novel Alzheimer's disease loci.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Article
- Taurine and Epidermal Growth Factor Belong to the Signature of First-Episode Psychosis.Frontiers in neuroscience · 2016Article
- LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy.Neurobiology of pain (Cambridge, Mass.)Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStructural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice.
resultsWe successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam.
conclusionsThe present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.
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