Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate.

Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na(+) channels as early as embryonic day 12. In this study, we investigated the role of these Na(+) channels in signaling during early development. In the neocortex of embryonic-day-13 mice, activation of Na(+) channels with veratridine induced a large Ca(2+) response throughout the neocortex, even in cell populations that lack the Na(+) channel. This Na(+)-dependent Ca(2+) activity requires external Ca(2+) and is completely blocked by inhibitors of Na(+)/Ca(2+) exchangers. Moreover, veratridine-induced Ca(2+) increase coincides with a burst of exocytosis in the PP. In parallel, we show that Na(+) channel stimulation enhances glutamate secretion in the neocortical wall. Released glutamate triggers further Ca(2+) response in PP and ventricular zone, as indicated by the decreased response to veratridine in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NMDA-receptor inhibitors. Therefore, the combined activation of the Na(+) channel and the Na(+)/Ca(2+) exchanger triggers Ca(2+) signaling in the PP neurons, leading to glutamate secretion, which amplifies the signal and serves as an autocrine/paracrine transmitter before functional synapses are formed in the neocortex. Membrane depolarization induced by glycine receptors activation could be one physiological activator of this Na(+) channel-dependent pathway.

High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats.

The subthalamic nucleus (STN) has come under focus in Parkinson disease (PD) because of recent advances in the understanding of the functional organization of the basal ganglia in normal and pathological conditions. Manipulations of the STN have been described to compensate for some imbalance in motor output of the basal ganglia in animal models of PD and have been proposed as a potential therapeutic target in humans. Indeed, high frequency stimulation (HFS) (130 Hz) of the STN has beneficial effects in severe parkinsonian patients but the precise mechanisms underlying these clinical results remain to be elucidated. To date, very little is known concerning the effect of HFS-STN on striatal dopaminergic transmission. Since it has been reported that dopaminergic medication may be reduced in PD patients under HFS-STN, our goal was to study the effect of HFS-STN on striatal dopamine (DA) transmission by using intracerebral microdialysis in normal and partially DA denervated rats. Our results show that HFS STN induces a significant increase of extracellular DA in the striatum of normal and partially DA lesioned rats while striatal extracellular levels of DOPAC were not affected. We conclude that HFS-STN acts directly and/or indirectly on striatal DA levels in control or partially DA lesioned rats.

Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat.

High frequency stimulation (130 Hz) of the subthalamic nucleus has dramatic beneficial motor effects in severe parkinsonian patients. However, the mechanisms underlying these clinical results remain obscure. The objective of the present work was to study the neurochemical changes induced in rats by high frequency stimulation of the subthalamic nucleus by using intracerebral microdialysis within its target structures. Our results show that high frequency stimulation of the subthalamic nucleus induces a significant increase of extracellular glutamate levels in the ipsilateral globus pallidus and substantia nigra while GABA was augmented only in the substantia nigra. These data suggest that functional effects induced by high frequency stimulation of the subthalamic nucleus might imply distal mechanisms involving the synaptic relationships with the subthalamic efferences. They question the current view that the direct inhibition of the subthalamic neurons is induced by high frequency stimulation.

A paradoxical increase in resting energy expenditure in malnourished patients near death: the king penguin syndrome.

BACKGROUND: The metabolic expression of extreme starvation on the verge of death is unknown in humans. OBJECTIVE: The objective was to compare the resting energy expenditure (REE) of 5 extremely malnourished dying patients [body mass index (in kg/m(2)): 9.77 +/- 0.1] with that of 16 less-malnourished anorexia nervosa (AN) patients. DESIGN: REE was measured by indirect calorimetry and body composition was measured by anthropometry and dual-frequency bioelectrical impedance analysis. Fasting serum insulin, thyroid hormone, and catecholamine concentrations were also determined. RESULTS: At the start of refeeding, REE was high in each of the 5 extremely malnourished dying patients, whereas it was low in the 16 AN patients (mean +/- SD: 5174 +/- 391 kJ/d compared with 3844 +/- 619 kJ/d; P < 0.05). The high REE value in the 5 extremely malnourished dying patients was associated with almost no fat mass (FM), high urinary nitrogen loss (16.4 +/- 2.9 g/d), low serum fatty acid concentrations (0.36 +/- 0.23 mmol/L), and low or normal serum insulin, thyroid hormone, and catecholamine concentrations. During the first 2-4 wk of refeeding, REE and nitrogen loss decreased, whereas fatty acid concentrations increased in each of the 4 surviving patients; REE and urinary nitrogen output increased in the 16 AN patients. CONCLUSION: In malnourished persons near death, there is an increase in REE and in protein catabolism. The reason for this increase is unknown but could relate to consumption of the last mobilizable muscle mass and to diseased cellular membranes.

Vitamin intakes (A, E, C, carotenes) in a French institution: assessment by the duplicate-diet method.

Duplicate meals of those eaten by 14 healthy young males (25-35 years of age), usual hospital diets for breakfast, lunch, and dinner, were collected for 5 consecutive days and freeze-dried. Fat-soluble vitamin (alpha-, beta-, gamma-, and delta-tocopherols, retinol, alpha- and beta-carotenes) and vitamin C contents were analyzed. Duplicate meals presented a wide range in vitamin levels. Large individual day-to-day variations were observed. The median daily intakes (n =70) of retinol equivalent (0.31 mg/day) and tocopherol equivalent (3.48 mg/day) were low. Only one third of the meals could provide sufficient amounts of fat-soluble vitamins, whereas vitamin C intakes were adequate (87.4 mg/day). So, fat-soluble recommended intakes were not supplied for most of the subjects in this study.