Cerebral Glutamic Acid Decarboxylase Activity and γ‐Aminobutyric Acid Concentrations in Mice Susceptible or Resistant to Audiogenic Seizures

Abstract

DBA/2 mice between 21 and 28 days of age are highly susceptible to sound-induced seizures. Drug studies suggest a possible deficit of gamma-aminobutyric acid (GABA)-mediated neurotransmission may be involved. We have measured the whole brain GABA concentration and glutamic acid decarboxylase activity in DBA/2 mice at various ages before, during, and after the period of maximal susceptibility to audiogenic seizures. Corresponding determinations were carried out on age-matched TO mice, a strain much less susceptible to audiogenic seizures than DBA/2 mice at all ages. No significant differences in GABA concentration or glutamic acid decarboxylase activity were found between strains at any age. The susceptibility of DBA/2 mice to audiogenic seizures does not result from a gross inability to synthesise or store GABA.

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

“…No difference is observed in the GABA cerebral level between DBA/2 mice and control mice within the age range of 8-43 days, nor are there abnormalities in the brain levels of glutamic acid decarboxylase (GAD) and GABA synthesizing enzyme [32,58]. However, in brain slices of DBA/2 mice at 30 days of age, the K + -stimulated release of GABA is considerably lower than that of C57 mice [35].…”

Alterations in Uptake and Release Rates for GABA, Glutamate, and Glutamine During Biochemical Maturation of Highly Purified Cultures of Cerebral Cortical Neurons, a GABAergic Preparation

“…Such neuronal cultures are prepared from approximately 15-day-old rat or mouse embryos (Hertz et al, 1984). and the relatively late maturation of GABA content (Agrawal et al, 1966;Cutler and Dudzinski, 1974;Coyle and Enna, 1976; Sykes and Horton, 1982). GABA transport processes (Johnston and Davies, 1974;Schousboe et al, 1976;Coyle and Enna, 1976), and glutamate decarboxylase (GAD) activity (Wu et al.…”

“…GABA transport processes (Johnston and Davies, 1974;Schousboe et al, 1976;Coyle and Enna, 1976), and glutamate decarboxylase (GAD) activity (Wu et al. 1976; Coyle and Enna, 1976; Sykes and Horton, 1982) in the mouse or rat brain in vivo makes it doubtful that they have reached optimal functional differentiation. This concept is supported by the fact that Borg et al (1980) have observed a steady increase in GABA uptake rate, and Hauser and Bernasconi (1980) and Snodgrass et al (1980) a continuous rise of GAD activity in cultured neurons over the first 2-4 weeks.…”

Glutamate receptor antagonists reduce spontaneous epileptiform activity in cortical wedges prepared from DBA/2 mice

“…The ontogeny of the seizures in this strain is agedependent, with approximately 95% of the mice aged between 21 and 28 days exhibiting severe, often fatal, audiogenic seizures (Collins 1972). The susceptibility and severity declines with age (Sykes and Horton 1982;Jobe et al 1991), and by the time these mice reach 80 days of age they are completely resistant to seizures (Seyfried 1979).…”

“…Physiological and biochemical studies have suggested that the charcteristic susceptibility to audiogenic seizures in DBA/2 mice results from a series of neurochemical abnormalities. Some studies have suggested that impairment of γ-aminobutyric acid (GABA) function is a possible factor in the age-dependent susceptibility of these mice Sykes and Horton 1982;Ticku 1979). GABA A receptor binding in this strain was reported to be lower when compared with other non-susceptible strains such as C57, B1/6 or TO (Olsen et al 1986), and this reduction in GABA binding in DBA/2 mice was correlated with the age of susceptibility to seizures (Jobe et al 1991).…”