title: Subunit composition of neurotransmitter receptors in the immature and in the epileptic brain.
abstract: Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments.
authors.affiliation: Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue Fegan 9, Boston, MA 02115, USA ; Department of Child Neurology, Hospital Sant Joan de Déu, University of Barcelona, Passeig Sant Joan de Déu 2, Esplugues de Llobregat, 08950 Barcelona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Sánchez Fernández
authors.affiliation: Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue Fegan 9, Boston, MA 02115, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Loddenkemper
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists / Q000627:therapeutic use; D006801:Humans; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D021122:Protein Subunits; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate