Epileptic seizures induced by N-acetyl- l-aspartate in rats: in vivo and in vitro studies

• Published in: Brain research Vol. 861; no. 1; pp. 143 - 150
• Main Authors: Akimitsu, Tomohide, Kurisu, Kaoru, Hanaya, Ryosuke, Iida, Koji, Kiura, Yoshihiro, Arita, Kazunori, Matsubayashi, Hiroaki, Ishihara, Kumatoshi, Kitada, Kazuhiro, Serikawa, Tadao, Sasa, Masashi
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 07.04.2000; Amsterdam Elsevier; New York, NY
• Subjects: Absence-like seizure; Animals; Aspartic Acid - adverse effects; Aspartic Acid - analogs & derivatives; Aspartic Acid - genetics; Biological and medical sciences; Depolarization with repetitive firing; Electroencephalography - drug effects; Epilepsy - chemically induced; Epilepsy - genetics; Epilepsy - physiopathology; Frontal Lobe - drug effects; Frontal Lobe - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampal CA3 neuron; Hippocampus - drug effects; Hippocampus - physiology; Male; Medical sciences; N-acetyl- l-aspartate (NAA); N-Acetyl-L-aspartic acid; Nervous system (semeiology, syndromes); Neurology; Polyspike and spike-wave-like complex; Rats; Rats, Inbred WKY; Rats, Wistar; Status epilepticus; Tremor rat; Polyspike and spike-wave-like complex; N-acetyl- l-aspartate (NAA); Hippocampal CA3 neuron; Absence-like seizure; Status epilepticus; Depolarization with repetitive firing; Tremor rat; Nervous system diseases; Rat; Epilepsy; Rodentia; Central nervous system; Discharge pattern; Electrophysiology; Petit mal; Electroencephalography; In vitro; Cerebral disorder; In vivo; Vertebrata; Mammalia; Animal; Central nervous system disease; Hippocampus; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02028-X

Tremor rat ( tm/tm), the parent strain of spontaneously epileptic rat (SER: zi/zi, tm/tm), exhibits absence-like seizures characterized by 5–7 Hz spike-wave-like complexes on cortical and hippocampal electroencephalograms (EEG) after 10 weeks of age, prior to development of convulsive seizures. Recently, this animal model has been demonstrated to display a genomic microdeletion within the critical region of tm, where aspartoacylase hydrolyzing N-acetyl- l aspartate (NAA) is located, besides showing the ability to accumulate NAA in the brain. Therefore, the present study was performed to determine the involvement of NAA in the induction of epileptic seizures. When NAA (4 μmol) was applied intracerebroventricularly (i.c.v.) to normal Wistar rats, 4–10 Hz polyspikes and/or spike-wave-like complexes followed by absence-like seizure before persistent 1–5 Hz waxing high-voltage after-discharges were observed on cortical and hippocampal EEG. At a higher dose (8 μmol), NAA induced convulsive seizures. The absence-like seizures with polyspikes and/or spike-wave-like complexes on the EEG were also observed with i.c.v. NAA in premature tremor rats without seizures. The NAA-induced seizures in normal rats were antagonized by i.c.v. glutamic acid diethyl ester, a non-selective glutamate receptor antagonist. In addition, NAA applied to the bath rapidly induced a long-lasting depolarization concomitantly with repetitive firings in hippocampal CA3 neurons of normal rat brain slice preparations. These findings suggest that NAA is involved in the induction of absence-like seizures and/or convulsion, probably via glutamate receptors.