Journal de physiologie最新文献

The availability of relatively large amounts of nerve growth factor (NGF) has allowed extensive in vitro and in vivo characterization of the neuronal specificity of this neurotrophic factor. The restricted neuronal specificity of NGF (sympathetic neurons, neural crest-derived sensory neurons, basal forebrain cholinergic neurons) has long predicted the existence of other neurotrophic factors possessing different neuronal specificities. Whereas there have been many reports of "activities" distinct from NGF, full characterization of such molecules has been hampered by their extremely low abundance. The recent molecular cloning of brain-derived neurotrophic factor (BDNF) revealed that this protein is closely related to NGF and suggested that these two factors might be members of an even larger gene family. A PCR cloning strategy based on homologies between NGF and BDNF has allowed us to identify and clone a third member of the NGF family which we have termed neurotrophin-3 (NT-3). The establishment of suitable expression systems has now made available sufficient quantities of these proteins to allow us to begin to establish the neuronal specificity of each member of the neurotrophin family, and the role of each in development, maintenance and repair of the PNS and CNS. Using primary cultures of various PNS and CNS regions of the developing chick and rat, and Northern blot analysis, we describe novel neuronal specificities of BDNF, NT-3 and an unrelated neurotrophic factor-ciliary neurotrophic factor (CNTF).

This paper shows a medial prefrontal cortex (CxAP9) facilitating influence upon the unit activity of the centralis lateralis (Cl) nucleus of the thalamus, in rats anesthetized with urethane. Cortical influences were studied using both cortical cooling and cortical spreading depression (CSD) procedures. Both spontaneous and noxious thermally evoked activities were considered. When CSD was propagated and affected the CxAP9, as well as during the cooling of this area, both spontaneous activity and the responses evoked in Cl cells by noxious stimulation were blocked. This effect was interpreted as a cortical disfacilitation upon Cl cells. During the cortical silent period we tested the excitability of a few Cl cells, provoking their activation by passing electrical current across the same Cl recording electrode. No changes were observed in their excitable response threshold during CSD or cortical cooling. Our results are in agreement with the proposition of a tonic cortical facilitatory action upon the spontaneous and noxious-evoked responses recorded in the Cl cells.

1.) Total renin, active renin, prorenin, angiotensin II, estradiol and progesterone were measured in maternal, placental and fetal blood and in trophoblastic and uterine tissues of the guinea pig. Furthermore, membrane angiotensin II receptors were measured in trophoblastic tissues. 2.) Blood and tissue concentrations of total renin, active renin, angiotensin II and steroids are shown to increase with gestational age. At the full term of pregnancy (70th post-coital day), tissue concentrations of total renin in chorion (23,900 +/- 2,752 ng/g of tissue/h), maternal placenta (14,210 +/- 1,131), fetal placenta (12,475 +/- 927) and uterus (7,677 +/- 798) are 100 time higher than those observed in placental, fetal and maternal blood. Distribution of blood and tissue prorenin (inactive renin) is similar to that found for total renin. Active renin/Total renin ratio reaches 1% in uterine, placental and chorion tissues and 9.3 +/- 1.0% in maternal, placental and fetal blood. 3.) Angiotensin II levels in systemic maternal blood (690 +/- 99 pg/ml) and in uterine blood (467 +/- 84) are higher than those found in placental blood (266 +/- 39) and in different trophoblastic tissues (between 200 and 400 pg/g). Angiotensin II receptor concentrations are highest in chorion. 4.) Regarding the steroid hormones, it is noted that placental and maternal blood contain more progesterone than trophoblastic tissues. The highest concentrations of estradiol are found in chorion tissue and uterine blood. 5.) A positive correlation is observed between angiotensin II and estradiol in uterine blood (r = 0.69, P less than 0.01) and in chorion (r = 0.71, P less than 0.01). These findings indicate that angiotensin II and estradiol could, by their interactions, play an important role in the physiology of pregnancy.

The experiments reported here attempted to examine in two groups of rats the effects on the taste preferences, food and fluid intake, energy balance and body weight gain of corticocerebellar lesions involving, primarily, the Lobulus VI (LVI) or the Lobulus Paramedianus (LP). The results showed that the lesions of LVI or LP did not affect the daily intake of total fluid and salty solution. The intake of sweet solution increased in both groups of lesioned rats, while the intake of deionized water and acid and bitter solutions decreased only in the LVI lesioned rats. Food intake decreased in the LVI-lesioned rats but not in the LP-lesioned animals. Body weight gain, efficiency of food utilization, caloric intake and body surface gain decreased in both groups. It seems therefore that the cerebellar cortex, which probably receives taste fibers, somehow influences taste preferences and water intake, and that it may be involved in the mechanisms of food intake, its utilization and body energy balance.

The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. We discuss the implications of these results in the context of Parkinson disease.

Synaptic vesicles participate in a cycle of fusion with the plasma membrane and reformation by endocytosis. Endocytosis of membrane proteins by the well studied clathrin-coated vesicle pathway has been shown to involve specific sequences within the cytoplasmic tail domain. Proteins taken up by clathrin-coated vesicles are directed to early endosomes from which they may return to plasma membrane. Recent evidence suggests that the synaptic vesicle protein synaptophysin is targeted to early endosomes in transfected fibroblasts and in neuroendocrine cells. To begin to test whether sequences within the COOH-cytoplasmic domain are required for internalization we have expressed a synaptophysin molecule lacking this domain in 3T3 cells and measured its rate of internalization. While a full length synaptophysin was internalized efficiently, we could not detect internalization of the mutant construct. These data are consistent with a model in which the COOH-terminal tail is required for coated-pit localization and hence targeting of synaptophysin to early endosomes.

To determine if there was a role for the submucosal nerves in cholera toxin (CT)-induced secretion, we studied the effects of serosal addition of two neurotoxins, the nerve conduction blocking agent, tetrodotoxin (TTX), and the nicotinic ganglionic blocking agent, hexamethonium (HXM), on electrolyte secretion in control isolated rabbit ileum and in that stimulated by CT. 1). In the absence of CT, the short circuit current (Isc) decreased after TTX (10(-7) M) (P less than 0.01) and was unaltered by HXM (10(-5) M). In the presence of CT, Isc increased but was not modified by 10(-7) M TTX or 10(-5) M HXM. 2) In control tissues the mean isotopic Na+ and Cl- fluxes were not significantly altered by TTX addition. Cl- absorption alone was significantly reduced by HXM (delta JCl- = 1.95 +/- 0.81 microEq.hr-1.cm-2; P less than 0.02). After stimulation with CT, TTX significantly inhibited Na+ and Cl- secretion (delta JNa+ = 2.15 +/- 0.61 and delta JCl- = 2.15 +/- 0.76 microEq.hr-1.cm-2; P less than 0.01). Similarly, HXM significantly inhibited CT-stimulated Na+ and Cl- secretion (delta JNa+ = 1.73 +/- 0.70 and delta JCl- = 1.46 +/- 0.62 microEq.hr-1.cm-2; P less than 0.02). 3) In TTX and HXM treated tissues there was no difference in the increase in Isc caused by cAMP (2 x 10(-3) M), calcium ionophore A 23187 (4 x 10(-6) M) and glucose (10(-3) M) compared to the untreated tissues in the presence or absence of CT.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Central pattern generators (CPGs) underlie a wide variety of rhythmic behaviours such as locomotion and respiration in most multi-cellular organisms. 2. The CPG's are capable of generating a patterned output without phasic sensory input. 3. The organization of the CPG is due to both intrinsic properties of the individual neurons and their network interactions. 4. To gain an understanding of the mechanisms which underlie rhythmicity a CPG has been reconstructed in culture. This will allow investigators to test directly the mechanisms underlying the generation of rhythmic output and will allow the direct testing of the mechanisms by which various modulators affect the CPG.

In spite of considerable advances towards understanding lineages derived from neural crest cells using amphibian and avian embryos, the molecular mechanisms involved in the formation of mammalian peripheral ganglia remain largely unknown, mainly because of the lack of experimental systems that will allow their in vitro manipulation. Here, we present a novel mammalian in vitro model permitting to study gangliogenesis from neural crest cells. This model allowed us to manipulate molecules involved in cell-cell interactions. Our data are in favour of the existence of a hierarchy among adhesion molecules.

The physiological, morphological and biochemical effects of type A Botulinum toxin (BoTX) were analysed in the electric organ of Torpedo, a modified neuromuscular system. The quantal content of the postsynaptic potential, or electroplaque potential (EPP), was reduced by BoTX but the quantum size remained unchanged till complete failure of the neurally evoked transmission. BoTX also suppressed the occurrence of spontaneous electroplaque potentials (MEPPs) of a quantal size but potentials of a smaller amplitude still kept on occurring in the intoxicated synapses. BoTX inhibited the evoked release of acetylcholine (ACh; biochemically measured) but the rate of spontaneous ACh release transiently increased during the period when evoked release went down. On the other hand, there were no significant change of ACh content, of ACh turnover, of ACh repartition in the vesicular and free compartments, or in the number of synaptic vesicles. Surprisingly, the amount of ATP was reduced to 50% in BoTX treated tissue at the time of transmission failure; also the level of creatine phosphate (CrP) was lowered to less than 20% and the rate of activity of creatine kinase was reduced. It was concluded that, electrophysiologically, BoTX affects synaptic transmission in a very similar way in the electric organ and in the neuromuscular junctions. On the other hand, the shortage of ATP supply found in the present study may play a role in the pathophysiology of intoxication and should be taken into account in investigations designed to see whether BoTX affects various phosphorylations in cholinergic nerve terminals.