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To clarify the acute-phase response in brain, we investigated the induction of metallothionein (MT) genes by administering an endotoxin (lipopolysaccharide) in rat intraperitoneum. We performed in situ hybridization on the serial brain sections to identify the cells expressing the MT genes in the acute-phase. After endotoxin administration, transcripts of MT genes were detected in the arachnoideal, ependymal cells and the Bergmann glia of the cerebellum, while no significant induction of the MT genes by zinc ion was observed in the brain. These results suggest that the acute-phase response occurs specifically in at least these three non-neuronal cells.

The effect of immersion stress on guanidino compounds in rat organs was studied. Short-term (5min) immersion stress increased the creatinine level in the cerebral cortex and the homoarginine level in the cerebellum, but it did not affect guanidino compound levels in the liver, kidney and pancreas. On the other hand, long-term (60min) immersion stress decreased the creatinine level in the liver and the arginine level in the kidney, and increased the arginine and γ-guanidinobutyric acid levels in the liver. However, long-term immersion stress did not affect guanidino compound levels in the brain or pancreas. Further, long-term immersion stress increased the excretion of γ-guanidinobutyric acid in the urine. These findings suggest that the transient increases of creatinine in the cerebral cortex and homoarginine in the cerebellum might be related to a functional change in the central nervous system during the early stage of immersion stress. It is thought that the long-term immersion stress affects guanidino compound metabolism in the peripheral organs through changes in protein metabolism.Administration of imipramine reduced the lowered mood induced in rats by immersion stress, but it did not affect the change in guanidino compound levels induced by long-term immersion stress. This result suggests that the alleviation of the lowered mood induced in rats by imipramine treatment is not related to changes in guanidino compound levels in rat organs.

Inbred mutant El mice are highly susceptible to convulsive seizures upon stimulation by "throwing". Amino acid levels were analyzed in the cortex, hippocampus, midrain, hypothalamus, pons-medulla oblongata and cerebellum of non-stimulated El mice [El(-)], of stimulated El mice [El(+)] during the interictal period and ddY mice (ddY) (controls) using an amino acid analyzer. Levels of aspartate, glutamate, glutamine and taurine were generally higher in the brains of E1 mice than those of ddY mice. Levels of aspartate, glutamate and GABA were lower in the brains of El(+) mice than those of El(-) mice. No significant difference was found in the hypothalamus. In addition, changes in amino acid levels were examined during the pre-convulsive stage, during convulsions and after convulsions of El(+) mice. The glutamate level was generally increased during the pre-convulsive stage, but other amino acids such as aspartate, glutamine, GABA and tauirne were decreased at that time compared to the interictal levels. These changes in amino acids were mostly found in the cortex, hippocampus and midbrain. These results suggest that glutamate may play a role in the triggering of seizures in El mice.

It is known that GABA is one of the important inhibitory chemical neurotransmitter substances in the central nervous system. Some neurochemical disorders, such as epileptic seizures, have been treated by reinforcement of the GABAergic transmission system. Recently we have studied the action of various GABA receptor modulators on induced seizures in El mice. An intraperitoneal injection of γ-vinyl GABA (a GABA transaminase blocker), 1500 mg/kg, completely inhibited El mouse seizures with significatly increased endogeneous GABA levels in the brain. Administration of 3 mg/kg of muscimol (a GABA agonist), i.p., completely inhibited the seizures with increased glutamine levels in the brain. Administration of 100 mg/kg of progabide (a GABA agonist), i.p., completely inhibited the seizures with no significant chnage in amino acids in the brain. An intraperitoneal injection of 32 mg/kg of diazepam completely inhibited the seizures with significantly increased glutamine levels in the brain. An intraperitoneal injection of 20 mg/kg of baclofen (an agonist for the GABA receptor) blocked the seizures with decreased levels of GABA, glutamic acid and alanine in the brain. These results suggest that inhibition of E1 mouse seizures may depend on an increased GABA level in the case of γ-vinyl GABA, on the action of a GABA receptor agonist in the case of muscimol and progabide, on the reinforcement of GABA receptor binding through benzodiazepine receptor in the case of diazepam, and on the action of a GABA(B) receptor agonist in the case of baclofen.