Oligodendroglia metabolically support axons and contribute to neurodegeneration

Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.     

New centrally acting drugs: Coumarin derivatives

Riassunto Si descrive una nuova classe di farmaci stimolanti il sistema nervoso centrale, rappresentata dalle aminometilidrossi- e dalle aminometilmetossicumarine N-sostituite.L'attività di questi nuovi composti è inferiore a quella dei corrispondenti isomeri derivati dal cromone e dal flavone.     

VIP and noradrenaline act synergistically to increase cyclic AMP in cerebral cortex

There is growing evidence that two, or possibly more, neurotransmitters can coexist within the same neurone. In particular, the presence of a peptide and a biogenic amine has been demonstrated in the same terminals of central and peripheral neurones. These findings have led to the hypothesis that neurotransmitters, coexisting within the same neurones, can interact at pre- or postsynaptic sites in a functionally coordinated manner. However, interactions between neurotransmitters contained in distinct neuronal systems terminating within the same region of the central nervous system (CNS) can be envisaged. We have examined this last possibility in the cerebral cortex, an area of the CNS where the two neurotransmitters vasoactive intestinal polypeptide and noradrenaline are contained in separate neuronal systems and where they both stimulate the formation of cyclic AMP. We report here that vasoactive intestinal polypeptide and noradrenaline act synergistically to stimulate the formation of cyclic AMP and that this synergistic interaction is antagonized by the specific alpha-adrenergic antagonist phentolamine.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analog, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.     

Prostaglandins and the synergism between VIP and noradrenaline in the cerebral cortex

We have previously shown that vasoactive intestinal peptide (VIP) and noradrenaline (NA) interact synergistically to increase cyclic AMP levels in mouse cerebral cortical slices. The pharmacological mechanism of this synergism is the potentiation by NA, through alpha 1 adrenergic receptors, of the stimulatory effect of VIP on cAMP formation. A similar interaction has been confirmed in guinea pig cerebral cortex and in discrete nuclei of the rat hypothalamus. Furthermore VIP and NA interact synergistically to depress the spontaneous activity of identified neurons in rat neocortex. At the cellular level, this synergistic interaction suggests that VIP- and NA-containing neuronal systems may converge, at least in part, on the same target cells to increase cAMP levels in the cerebral cortex. At the molecular level, the interaction may occur at various steps in signal transduction, between receptors, intramembrane transduction processes or intracellular effector mechanisms. Here we report that the alpha 1-adrenergic potentiation of the increases in cAMP elicited by VIP involves the formation of arachidonic acid metabolites and is mimicked by prostglandins F2 alpha and E2.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Summary Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analogs, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.Acknowledgments. Supported by SNSF grant No. 3.327.078. The authors express their gratitude to Miss G. Allenbach for her excellent technical assistance and to Mr F. Pillonel for drawing the graphs.