Glutamatergic System is Affected in Brain from an Hyperthermia-Induced Seizures Rat Model

Abstract

One of the most frequent neurological disorders in children is febrile seizures (FS), a risk for epilepsy in adults. Glutamate is the main excitatory neurotransmitter in CNS acting through ionotropic and metabotropic receptors. Excess of glutamate in the extracellular space elicits excitotoxicity and has been associated with neurological disorders, such as epilepsy. The removal of extracellular glutamate by excitatory amino acid transporters (EATT) plays an important neuroprotective role. GLT-1 is the main EAAT present in the cortex brain. On the other hand, an increase in metabotropic glutamate receptors 5 (mGlu5R) levels or their overstimulation have been related to the appearance of seizure events in different animal models and in temporal lobe epilepsy in humans. In this work, the status of several components of the glutamatergic system has been analysed in the cortex brain from an FS rat model at short (48 h) and long (20 days) term after hyperthermia-induced seizures. At the short term, we detected increased GLT-1 levels, reduced glutamate concentration, and unchanged mGlu5R levels, without neuronal loss. However, at the long term, an increase in mGlu5R levels together with a decrease in both GLT-1 and glutamate levels were observed. These changes were associated with the appearance of an anxious phenotype. These results suggest a neuroprotective role of the glutamatergic components mGlu5R and GLT-1 at the short term. However, this neuroprotective effect seems to be lost at the long term, leading to an anxious phenotype and suggesting an increased vulnerability and propensity to epileptic events in adults.

Graphic Abstract

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was funded by Ministerio de Ciencia e Innovación (Grant PID2019-109206 GB-I00), by UCLM (Grant 2020-GRIN-29108 cofinanced with the European Union FEDER), and by Junta de Comunidades de Castilla-La Mancha (JCCM) (Grant SBPLY/19/180501/000251). M.C. is the recipient of a post-doctoral grant (01150PO906) from JCCM cofinanced with the European Union FEDER.

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Crespo, M., León-Navarro, D.A. & Martín, M. Glutamatergic System is Affected in Brain from an Hyperthermia-Induced Seizures Rat Model. Cell Mol Neurobiol (2021). https://doi.org/10.1007/s10571-021-01041-2

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Keywords

  • Glutamate
  • Metabotropic glutamate receptor
  • Hyperthermia seizure
  • Epilepsy