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Kainic acid-induced status epilepticus decreases mGlu5 receptor and phase-specifically downregulates Homer1b/c expression

(2020) BRAIN RESEARCH. 1730.
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Abstract
Globally, over 50 million people are affected by epilepsy, which is characterized by the occurrence of spontaneous recurrent seizures. Almost one-third of the patients show resistance to current anti-epileptic drugs, making the exploration of new molecular targets necessary. An interesting target may be Homerl, due to its diverse roles in epileptogenesis and synaptic plasticity. Indeed, Homerl regulates group I metabotropic glutamate (mGlu) receptors (i.e. mGlu(1) and mGlu(5)) scaffolding and signaling in neurons. In the present work, using the systemic kainic acid (KA)-induced status epilepticus (SE) model in adult rats, we investigated the mRNA and protein expression patterns of the mGlu5 receptor, Homerla and Homerlb/c at 10, 80 and 120 days post-SE (i.e. T10, T80 and T120). Epileptogenesis was validated by electrophysiological recordings of seizures via electroencephalography (EEG) monitoring and through upregulation of glial fibrillary acidic protein. At the protein level, the mGlu5 receptor was downregulated in the late latent phase (T10) and the early- and late exponential growth phase (T80 and T120, respectively), which was best observed in the hippocampal CA1 region. At mRNA level, significant downregulation of the mGlu5 receptor was only detected in the late exponential growth phase. Homerla expression did not change at any investigated time point. Interestingly, Homerlb/c was only downregulated in the late latent phase, a period where spontaneous seizures are extremely rare. Thus, this phasespecific downregulation may be indicative of an endogenous neuroprotective mechanism. In conclusion, these results suggest that Homerlb/c may be an interesting molecular target to prevent epileptogenesis and/or control seizures.
Keywords
Developmental Biology, General Neuroscience, Molecular Biology, Clinical Neurology, Homer1, mGlu(5) receptor, Temporal lobe epilepsy, Kainic acid, Epileptogenesis, Hippocampus, METABOTROPIC GLUTAMATE RECEPTORS, TEMPORAL-LOBE EPILEPSY, MENTAL-RETARDATION PROTEIN, LONG-TERM DEPRESSION, MESSENGER-RNA, RAT MODEL, ENDOPLASMIC-RETICULUM, INDUCED SEIZURES, GENE-EXPRESSION, UP-REGULATION

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MLA
Crans, René, et al. “Kainic Acid-Induced Status Epilepticus Decreases MGlu5 Receptor and Phase-Specifically Downregulates Homer1b/c Expression.” BRAIN RESEARCH, vol. 1730, 2020.
APA
Crans, R., Daelemans, S., Raedt, R., Ciruela, F., & Stove, C. (2020). Kainic acid-induced status epilepticus decreases mGlu5 receptor and phase-specifically downregulates Homer1b/c expression. BRAIN RESEARCH, 1730.
Chicago author-date
Crans, René, Sofie Daelemans, Robrecht Raedt, Francisco Ciruela, and Christophe Stove. 2020. “Kainic Acid-Induced Status Epilepticus Decreases MGlu5 Receptor and Phase-Specifically Downregulates Homer1b/c Expression.” BRAIN RESEARCH 1730.
Chicago author-date (all authors)
Crans, René, Sofie Daelemans, Robrecht Raedt, Francisco Ciruela, and Christophe Stove. 2020. “Kainic Acid-Induced Status Epilepticus Decreases MGlu5 Receptor and Phase-Specifically Downregulates Homer1b/c Expression.” BRAIN RESEARCH 1730.
Vancouver
1.
Crans R, Daelemans S, Raedt R, Ciruela F, Stove C. Kainic acid-induced status epilepticus decreases mGlu5 receptor and phase-specifically downregulates Homer1b/c expression. BRAIN RESEARCH. 2020;1730.
IEEE
[1]
R. Crans, S. Daelemans, R. Raedt, F. Ciruela, and C. Stove, “Kainic acid-induced status epilepticus decreases mGlu5 receptor and phase-specifically downregulates Homer1b/c expression,” BRAIN RESEARCH, vol. 1730, 2020.
@article{8655090,
  abstract     = {Globally, over 50 million people are affected by epilepsy, which is characterized by the occurrence of spontaneous recurrent seizures. Almost one-third of the patients show resistance to current anti-epileptic drugs, making the exploration of new molecular targets necessary. An interesting target may be Homerl, due to its diverse roles in epileptogenesis and synaptic plasticity. Indeed, Homerl regulates group I metabotropic glutamate (mGlu) receptors (i.e. mGlu(1) and mGlu(5)) scaffolding and signaling in neurons. In the present work, using the systemic kainic acid (KA)-induced status epilepticus (SE) model in adult rats, we investigated the mRNA and protein expression patterns of the mGlu5 receptor, Homerla and Homerlb/c at 10, 80 and 120 days post-SE (i.e. T10, T80 and T120). Epileptogenesis was validated by electrophysiological recordings of seizures via electroencephalography (EEG) monitoring and through upregulation of glial fibrillary acidic protein. At the protein level, the mGlu5 receptor was downregulated in the late latent phase (T10) and the early- and late exponential growth phase (T80 and T120, respectively), which was best observed in the hippocampal CA1 region. At mRNA level, significant downregulation of the mGlu5 receptor was only detected in the late exponential growth phase. Homerla expression did not change at any investigated time point. Interestingly, Homerlb/c was only downregulated in the late latent phase, a period where spontaneous seizures are extremely rare. Thus, this phasespecific downregulation may be indicative of an endogenous neuroprotective mechanism. In conclusion, these results suggest that Homerlb/c may be an interesting molecular target to prevent epileptogenesis and/or control seizures.},
  articleno    = {146640},
  author       = {Crans, René and Daelemans, Sofie and Raedt, Robrecht and Ciruela, Francisco and Stove, Christophe},
  issn         = {0006-8993},
  journal      = {BRAIN RESEARCH},
  keywords     = {Developmental Biology,General Neuroscience,Molecular Biology,Clinical Neurology,Homer1,mGlu(5) receptor,Temporal lobe epilepsy,Kainic acid,Epileptogenesis,Hippocampus,METABOTROPIC GLUTAMATE RECEPTORS,TEMPORAL-LOBE EPILEPSY,MENTAL-RETARDATION PROTEIN,LONG-TERM DEPRESSION,MESSENGER-RNA,RAT MODEL,ENDOPLASMIC-RETICULUM,INDUCED SEIZURES,GENE-EXPRESSION,UP-REGULATION},
  language     = {eng},
  pages        = {11},
  title        = {Kainic acid-induced status epilepticus decreases mGlu5 receptor and phase-specifically downregulates Homer1b/c expression},
  url          = {http://dx.doi.org/10.1016/j.brainres.2019.146640},
  volume       = {1730},
  year         = {2020},
}

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