Glutamate Levels in Cerebrospinal Fluid: Do they Reflect In Vivo Modifications in Neurological Disorders?

Abstract

Current evidence strongly suggests that glutamic acid is not only an intermediate of energy metabolism, but also the most important excitatory neurotransmitter in mammalian brain (Fonnum, 1984; Roberts et al., 1981). Moreover, high concentrations of glutamate can exert specific neurotoxic effects both in vivo and in vitro, which ultimately lead to neuronal degeneration and death due to continuous and uncontrolled excitatory activity (Olney and Sharpe, 1969). It is not surprising, therefore, that glutamate and other excitatory amino-acids are involved in many physiological functions as well as in the pathogenesis of different neuropsychiatric disorders (Table 1). Dysfunctions of these neurotransmitter systems have been demonstrated in various neurological disorders such as epilepsy (McDonald et al., 1991), diseases of the basal ganglia (Carlsson and Carlsson, 1990), senile dementia of Alzheimer’s type (Greenamyre et al., 1985 and 1988; Ellison et al., 1986; Chalmers et al., 1990), amyotrophic lateral sclerosis (Perry et al., 1987; Plaitakis and Caroscio, 1987; Plaitakis et al., 1988), progressive supranuclear palsy (Perry et aI., 1988) and cerebral ischemia (Rothman and Olney, 1986; Choi, 1988 and 1990). However, most of these studies were performed in autopsied brains and spinal cords, which reveal changes characteristic only of end-stage disease (Blin et al., 1990), or in animal models which are sometimes not very close to human disorders.