Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo.

Neuronal activity is tightly coupled with brain energy metabolism. Numerous studies have suggested that lactate is equally important as an energy substrate for neurons as glucose. Lactate production is reportedly triggered by glutamate uptake, and independent of glutamate receptor activation.

Effects of orally administered levodopa on mesencephalic dopaminergic neurons undergoing a degenerative process.

Although the issue of in vivo levodopa toxicity appears to be settled by now in the light of recent findings, a crucial aspect was not accounted for the experiments designed to tackle that question. Levodopa could in fact be non-toxic on surviving dopamine neurons, but that could not be the case when the drug is administered at the same time those neurons are undergoing degeneration, which is what happens in the clinical setting. Dopaminergic neurons could in that situation be more vulnerable to levodopa's potential toxic action.

Differential activation of astrocytes and microglia during post-natal development of dopaminergic neuronal death in the weaver mouse.

In order to understand the relationship between astrocytes, microglia and injured neurons, we studied the weaver mutant mouse. One of the main characteristics of this mutant is the progressive degeneration of the dopaminergic (DA) nigrostriatal pathway that starts around postnatal day 15 (P15), in the substantia nigra pars compacta (SNpc) and progresses until adult age (P60). In the present paper, we analysed the relationship between astroglial and microglial cells within DA neurons in the nigrostriatal system of homozygous weaver mice, at different postnatal ages corresponding to specific stages of the DA neuronal loss.

Effect of chronic treatment with riluzole on the nigrostriatal dopaminergic system in weaver mutant mice.

The effects of a chronic treatment with the anti-glutamate and sodium channel modulating neuroprotective agent riluzole on the degeneration of dopamine-containing neurons were studied in the brain of weaver mutant mice. In these animals, as in Parkinson's disease, dopaminergic neurons of the nigro-striatal pathway undergo spontaneous and progressive cell death. Homozygous weaver mice were orally treated twice a day with either 8 mg/kg riluzole or placebo for 2 months.

Survival promotion of mesencephalic dopaminergic neurons by depolarizing concentrations of K+ requires concurrent inactivation of NMDA or AMPA/kainate receptors.

The death of dopaminergic neurons that occurs spontaneously in mesencephalic cultures was prevented by depolarizing concentrations of K+ (20-50 mM). However, unlike that observed previously in other neuronal populations of the PNS or CNS, promotion of survival required concurrent blockade of either NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors by the specific antagonists, MK-801 and GYKI-52466, respectively. Rescued neurons appeared to be healthy and functional because the same treatment also dramatically enhanced their capacity to accumulate dopamine.