2010
Volume 10, Number 3, p.p. 96–101
Toluene induced changes in excitatory amino acid metabolism during the sleep–wakefulness cycle
Guram G. Beradze,a Lali V. Shanshiashvili,b,c Isolda S. Chogovadze,c Irina V. Kalandadze,c
Nikoloz T. Oniani,c Jeremy J. Ramsdend,e and David G. Mikeladzec,*
a P. Shotadze Medical Academy, Tbilisi, Georgia
b Ilia State University, Tbilisi, Georgia
c I. Beritashvili Institute of Physiology, Tbilisi, Georgia
d Collegium Basilea, Institute of Advanced Study, Basel, Switzerland
e Cranfield University, Bedfordshire, England
Many occupational studies have inferred central nervous system dysfunction as an outcome of toluene exposure. The sleep–wakefulness cycle is a universal model of brain integrative activity, which reflects multiple levels of the homeostatic processes. In this study, the structure of the sleep–wakefulness cycle of the rat, the quantitative ratio of phases, their electrographic characteristics and changes in the content of intraventricular glutamate, aspartate and arginine were determined in the normal state, after 10 days inhalation of toluene, 5 days after its withdrawal and after the action of chlorogenic acid, one of the most abundant polyphenols in the human diet with antioxidant, anticarcinogenic and neuroprotective properties. Using electroencephalography for the determination of behavioural state we found that toluene inhalation disrupts the normal sleep cycle, increased the total length of wakefulness, suppressed REM sleep, and reduced non-REM sleep. We have furthermore shown that the content of intraventricular glutamate was increased in all states of the sleep–wakefulness cycle while the concentration of aspartate was decreased. Arginine was diminished during wakefulness and non-REM sleep and increased in REM sleep. Intraperitoneal administration of chlorogenic acid resulted in rapid normalization both of the duration of the sleep–wakefulness cycle and the amino acid contents. These findings suggest that toluene engenders disturbance of excitatory amino acid and nitric oxide metabolism, which is reflected in the dynamics of the sleep–wakefulness cycle and duration of its phases.
Keywords: aspartate, arginine, chlorogenic acid, glutamate, rat