Acute peripheral catecholaminergic changes in rat after MPTP and MPP+ treatment

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) on the peripheral catecholaminergic system of the rat were investigated. MPTP and MPP+ injections (20 mg/kg i.p.) caused a marked acute depletion of heart noradrenaline, up to 75% twelve hours after the administration, and a decrease of adrenal gland adrenaline. The time-course of the effect of MPTP and MPP+ is reported, together with a decrease in the tyrosine hydroxylase activity after MPTP treatment, more evident in the adrenal glands. Pargyline (50 mg/kg i.p.) is not able to prevent such a neurotoxic peripheral effect.     

Role of the peripheral catecholaminergic systems in the antistress action of neuropeptides

The mediator activity of the peripheral catecholaminergic systems (the adrenergic nerves of dura mater and the concentrations of noradrenaline and adrenaline in the adrenals of rats) during dynamic and immobilization stress was investigated with the help of fluorescent microscopy and spectrofluorometry. Neuropeptides--dalargin and another enkephalin analog--were injected intraperitoneally, 150 mg/kg. A visible antistress action of these neuropeptides has been demonstrated, it was more marked after treatment with dalargin. The role of peripheral catecholaminergic system in the mechanism of stress-protective effects of neuropeptides is discussed.     

A biochemical comparison of Xenopus laevis and mammalian myelin from the central and peripheral nervous systems.

Myelin purified from the central nervous system of Xenopus laevis contained the same major lipid and protein components as human myelin. However, some minor differences in the myelin proteins were noted. The Xenopus basic protein had a higher apparent mol wt. on sodium dodecyl sulfate gels than the corresponding mammalian protein. The absolute specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in the Xenopus myelin was considerably higher than in mammals. There were differences in the high mol wt. proteins, and the glycoproteins in Xenopus myelin were more heterogeneous than those in mammals. Peripheral myelin from Xenopus sciatic nerve was compared with that from the rat. The lipids in the two types of myelin were similar. There was a major glycoprotein in the Xenopus myelin corresponding to the P0 protein and a basic protein of slightly larger mol wt. than the P1 protein of rat myelin.     

Metabolic level and the function of the peripheral catecholaminergic systems in immobilization hypothermia in rats

Metabolic peculiarities were studied on the model of prolonged immobilization hypothermia in rats (body temperature +20 degrees C for 24 h). Stress reactions and the state of peripheral catecholaminergic systems were compared in hypo- and normothermia. A direct correlation was established between the intensity of metabolism and the mediator activity in adrenergic nerve structures.     

Two cortical systems for reaching in central and peripheral vision

Parietal lesions in humans can produce a specific disruption of visually guided hand movement, termed optic ataxia. The fact that the deficit mainly occurs in peripheral vision suggests that reaching in foveal and extrafoveal vision rely on two different neural substrates. In the present study, we have directly tested this hypothesis by event-related fMRI in healthy subjects. Brain activity was measured when participants reached toward central or peripheral visual targets. Our results confirm the existence of two systems, differently modulated by the two conditions. Reaching in central vision involved a restricted network including the medial intraparietal sulcus (mIPS) and the caudal part of the dorsal premotor cortex (PMd). Reaching in peripheral vision activated in addition the parieto-occipital junction (POJ) and a more rostral part of PMd. These results show that reaching to the peripheral visual field engages a more extensive cortical network than reaching to the central visual field.     

Quantitative changes in mRNA expression of glutamate receptors in the rat peripheral and central vestibular systems following hypergravity

In order to investigate the mechanisms responsible for adaptation to altered gravity, we assessed the changes in mRNA expression of glutamate receptors in vestibular ganglion cells, medial vestibular nucleus, spinal vestibular nucleus/lateral vestibular nucleus, cerebellar flocculus, and uvula/nodulus from rats exposed to hypergravity for 2 h to 1 week using real-time quantitative RT-PCR methods. The mRNA expression of GluR2 and NR1 receptors in the uvula/nodulus and NR1 receptors in the medial vestibular nucleus increased in animals exposed to 2 h of hypergravity, and it decreased gradually to the control level. The mRNA expression of GluR2 receptors in vestibular ganglion cells decreased in animals exposed to 1 week of hypergravity. Neither the metabotropic glutamate receptor 1 nor delta2 glutamate receptor in flocculus and uvula/nodulus was affected by a hypergravity load for 2 h to 1 week. It is suggested that the animals adapted to the hypergravity by enhancing the cerebellar inhibition of the vestibular nucleus neurons through activation of the NR1 and GluR2 receptors on the Purkinje cells in uvula/nodulus especially at the early phase following hypergravity. In the later phase following hypergravity, the animals adapted to the hypergravity by reducing the neurotransmission between the vestibular hair cells and the primary vestibular neurons via down-regulation of the postsynaptic GluR2 receptors in the vestibular periphery.     

Adaptive changes of locomotion after central and peripheral lesions

This paper reviews findings on the adaptive changes of locomotion in cats after spinal cord or peripheral nerve lesions. From the results obtained after lesions of the ventral/ventrolateral pathways or the dorsal/dorsolateral pathways, we conclude that with extensive but partial spinal lesions, cats can regain voluntary quadrupedal locomotion on a treadmill. Although tract-specific deficits remain after such lesions, intact descending tracts can compensate for the lesioned tracts and access the spinal network to generate voluntary locomotion. Such neuroplasticity of locomotor control mechanisms is also demonstrated after peripheral nerve lesions in cats with intact or lesioned spinal cords. Some models have shown that recovery from such peripheral nerve lesions probably involves changes at the supra spinal and spinal levels. In the case of somesthesic denervation of the hindpaws, we demonstrated that cats with a complete spinal section need some cutaneous inputs to walk with a plantigrade locomotion, and that even in this spinal state, cats can adapt their locomotion to partial cutaneous denervation. Altogether, these results suggest that there is significant plasticity in spinal and supraspinal locomotor controls to justify the beneficial effects of early proactive and sustained locomotor training after central (Rossignol and Barbeau 1995; Barbeau et al. 1998) or peripheral lesions.     

Effects of fetal growth retardation on the development of central and peripheral catecholaminergic pathways in the sheep.

Regional norepinephrine and dopamine content and cerebral alpha 1- and beta-adrenergic receptor mechanisms were studied in the brain of sham operated control and single umbilical artery ligation (SUAL) induced growth retarded newborn sheep. Brain sparing was evidenced by relative preservation of brain weight compared to other organ systems. Norepinephrine and dopamine content of the brain were not affected by SUAL. This is in contrast to decreased norepinephrine levels in the brown fat, a normally densely innervated peripheral tissue. Alpha 1- and beta-adrenergic receptor numbers and affinity states were similar between the two groups. Coupling between beta-receptor and guanine nucleotide stimulatory protein and agonist stimulated adenylyl cyclase activity were unaffected by SUAL. Brain regional DNA content and protein/DNA ratios were not different between the two groups. These data suggest that single umbilical artery ligation induced fetal growth retardation modifies peripheral but not central catecholaminergic pathways in the sheep. Both growth and expression of specific catecholaminergic signal transduction system are protected in the brain.     

Development of central and peripheral serotonin-producing systems in rats in ontogenesis

The work deals with study of development of central and peripheral serotonin-producing systems in rat ontogenesis before and after formation of the blood-brain barrier. By the method of highly efficient liquid chromatography it has been shown that the serotonin level in peripheral blood before formation of the blood-brain barrier (in fetuses and neonatal rats) is sufficiently high for realization of physiological effect on target cells and organs. At the period of formation of the blood-brain barrier the serotonin level in brain sharply rises, whereas the serotonin concentration and amount in blood plasma and duodenum increase insignificantly. Completion of formation of the blood-brain barrier is accompanied by a significant increase of the serotonin content in duodenum, probably for maintenance of the high serotonin level in blood. To evaluate secretory activity, the mean rate of daily serotonin increment in the studied tissues was calculated. In brain, this parameter was maximal at the period of formation of the blood-brain barrier-from the 4th to the 16th postnatal days. This allows thinking hat brain before formation of the blood-brain barrier is the most important source of serotonin in peripheral blood.     

Interactions between central glutamatergic,catecholaminergic and cholinergic systems with regard to locomotor activity in monoamine-depleted mice

Summary Following injection of 5µg of the competitive NMDA receptor antagonist AP-5 into the nucleus accumbens, but not following injection of the same dose into the dorsal striatum, a pronounced locomotor stimulation in monoamine-depleted mice was produced; the-adrenoceptor agonist clonidine (1 mg/kg) administered ip caused a marked potentiation of an intraaccumbens AP-5 (2.5µg) injection.On the other hand, 10µg of AP-5 combined with an ip injection of clonidine (1 mg/kg) caused a marked locomotor stimulation following local application into the dorsal striatum but not following application into the prefrontal cortex. Likewise, in combination with systemically administered clonidine, a substantial locomotor stimulation was observed after application of the muscarine receptor antagonist methscopolamine (62µg) into the dorsal striatum but not into the prefrontal cortex.This study suggests that NMDA receptors in the nucleus accumbens exert an inhibitory influence on locomotor activity. The dorsal striatum may also be involved in such control via NMDA and muscarinic receptors.     

Effects of dysthyroidism on central catecholaminergic neurons

After 15 years of research, it is clear that alterations in thyroidal status affect catecholaminergic neurons in the developing as well as in the adult brain. Experiments on fetal catecholaminergic brain areas grafted into the anterior eye chamber of adult thyroidectomized rat have shown the thyroid hormone dependency of the morphological differentiation of catecholaminergic neurons originating from the substantia nigra and the locus coeruleus. Furthermore, thyroid hormones also affect the metabolism of catecholaminergic neurons. Neonatal hypothyroidism induced either by ¹³¹I or by an antithyroid drug decreases the concentration of dopamine, noradrenaline and the activity of tyrosine hydroxylase at least in whole brain studies. Treatments with l-thyroxine of neonatally thyroidectomized rats reverse these neurochemical changes in a both time and dose dependent manner. These presynaptic modifications are associated with a decrease in the number of catecholaminergic receptors in different brain areas. On the opposite, experimental neonatal hyperthyroidism induced by daily administration of l-triiodothyronine increases the synthesis as well as the utilization of catecholamines. These changes are also associated with an alteration of catecholaminergic receptors. Despite numerous studies, there is, so far, no clear conclusion on the effects of neonatal dysthyroidism on the development of each catecholaminergic group. However, from these studies, it appears that the intensity of neonatal dysthyroidism greatly varies, depending of the monoamine and the brain area studied. The utilization of fetal brain cell cultures growing in a chemically defined medium has permitted to demonstrate the direct effect of thyroid hormones on fetal brain cells and the morphological effects of triiodothyronine on the size and the neurite length and arborization of fetal hypothalamic dopaminergic neurons.In the adult brain, hypothyroidism induced by surgical thyroidectomy, decreases the rate of catecholamines synthesis, decreases the number of alpha noradrenergic receptors and has no effect on striatal dopaminergic receptors. In contrast, hyperthyroidism increases the rate of catecholamines synthesis and induced an hypersensitivity of noradrenergic receptors. The intensity of the effects of dysthyroidism seems to be dependent on the monoamine and the brain area studied.In conclusion, it can be proposed that in the neonate thyroid hormones act on CA neuron activity mostly through a morphogenetic effect whereas in the adulthood they directly affect CA metabolism.     

State of the peripheral catecholaminergic systems during pharmacologic correction of immobilization stress using sodium oxybutyrate

Fluorescent microscopy and spectrofluorometry of biogenic amines were employed to study the peripheral catecholaminergic systems in immobilized rats which received sodium hydroxybutyrate. The content of catecholamines was measured in the adrenergic nerves of dura mater, vas deferens and chromaffin tissue of the adrenals. It was established that sodium hydroxybutyrate in a dose of 40 mg/kg intraperitoneally promoted returning to normal of the adrenergic mediator activity during alarm and resistance stages. The role of the peripheral catecholaminergic systems in the mechanism of the stress-protective effect of sodium hydroxybutyrate is discussed.     

Visceral nociception: peripheral and central aspects of visceral nociceptive systems

Discomfort and pain are the sensations most commonly evoked from viscera. Most nociceptive signals that originate from visceral organs reach the central nervous system (c.n.s.) via afferent fibres in sympathetic nerves, whereas parasympathetic nerves contain mainly those visceral afferent fibres concerned with the non-sensory aspects of visceral afferent function. Noxious stimulation of viscera activates a variety of specific and non-specific receptors, the vast majority of which are connected to unmyelinated afferent fibres. Studies on the mechanisms of visceral sensation can thus provide information on the more general functions of unmyelinated afferent fibres. Specific visceral nociceptors have been found in the heart, lungs, testes and biliary system, whereas noxious stimulation of the gastro-intestinal tract appears to be detected mainly by non-specific visceral receptors that use an intensity-encoding mechanism. Visceral nociceptive messages are conveyed to the spinal cord by relatively few visceral afferent fibres which activate many central neurons by extensive functional divergence through polysynaptic pathways. Impulses in visceral afferent fibres excite spinal cord neurons also driven by somatic inputs from the corresponding dermatome (viscero-somatic neurons). Noxious intensities of visceral stimulation are needed to activate viscero-somatic neurons, most of which can also be excited by noxious stimulation of their somatic receptive fields. The visceral input to some viscero-somatic neurons in the spinal cord can be mediated via long supraspinal loops. Pathways of projection of viscero-somatic neurons include the spino-reticular and spino-thalamic tracts. All these findings give experimental support to the 'convergence-projection' theory of referred visceral pain. Visceral pain is the consequence of the diffuse activation of somato-sensory nociceptive systems in a manner that prevents accurate spatial discrimination or localization of the stimuli. Noxious stimulation of visceral receptors triggers general reactions of alertness and arousal and evokes unpleasant and poorly localized sensory experiences. This type of response may be a feature of sensory systems dominated by unmyelinated afferent inputs.     

Quercetin ameliorates gamma radiation-induced DNA damage and biochemical changes in human peripheral blood lymphocytes

We investigated the radioprotective efficacy of quercetin (QN), a naturally occurring flavonoid against gamma radiation-induced damage in human peripheral blood lymphocytes and plasmid DNA. In plasmid study, QN at different concentrations (3, 6, 12, 24 and 48 microM) were pre-incubated with plasmid DNA for 1h followed by exposure of 6 Gy radiation. Among all concentrations of QN used, 24 microM showed optimum radioprotective potential. To establish the most effective protective concentration of QN in lymphocytes, the cells were pre-incubated with 3, 6, 12, 24 and 48 microM of QN for 30 min and then exposed to 4 Gy gamma-radiation. The concentration-dependent effects of QN were evaluated by scoring micronuclei (MN) frequencies. The results showed that QN decreased the MN frequencies dose dependently, but the effect was more pronounced at 24 microM. Thus, 24 microM of QN was selected as the optimum concentration and was further used to evaluate its radioprotective effect in lymphocytes. For that a separate experiment was carried out, in which lymphocytes were incubated with QN (24 microM) for 30 min and exposed to different doses of radiation (1, 2, 3 and 4 Gy). Genetic damage (MN, dicentric aberration and comet attributes) and biochemical changes were measured to evaluate the effect of QN on gamma-radiations (1-4 Gy). Radiation exposed showed significant increases in the genetic damage and thiobarbituric acid reactive substances (TBARS) accompanied by a significant decrease in the antioxidant status. QN pretreatment significantly decreased the genetic damage and TBARS and improved antioxidant status through its antioxidant potential. Altogether, our findings encourage further mechanistic and in vivo studies to investigate radioprotective efficacy of QN.     

Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems

Constitutive activation of the Notch pathway can promote gliogenesis by peripheral (PNS) and central (CNS) nervous system progenitors. This raises the question of whether physiological Notch signaling regulates gliogenesis in vivo. To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS progenitors using Wnt1-Cre or Nestin-Cre. Rbpsuh encodes a DNA-binding protein (RBP/J) that is required for canonical signaling by all Notch receptors. In most regions of the developing PNS and spinal cord, Rbpsuh deletion caused only mild defects in neurogenesis, but severe defects in gliogenesis. These resulted from defects in glial specification or differentiation, not premature depletion of neural progenitors, because we were able to culture undifferentiated progenitors from the PNS and spinal cord despite their failure to form glia in vivo. In spinal cord progenitors, Rbpsuh was required to maintain Sox9 expression during gliogenesis, demonstrating that Notch signaling promotes the expression of a glial-specification gene. These results demonstrate that physiological Notch signaling is required for gliogenesis in vivo, independent of the role of Notch in the maintenance of undifferentiated neural progenitors.     

Effect of quercetin on nicotine-induced biochemical changes and DNA damage in rat peripheral blood lymphocytes

We elucidated the protective effect of quercetin, a polyphenolic flavonoid, on lipid peroxidation, endogenous antioxidant status and DNA damage during nicotine-induced toxicity in cultured rat peripheral blood lymphocytes as compared to N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine (3 mM) with and without quercetin and NAC (1 mM) in RPMI-1640 medium for 1 h. In preliminary experiments to fix the effective dose of quercetin, different doses of quercetin (25, 50, 75, 100 and 200 microM) were administered to lymphocytes with nicotine, and lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) were analysed. A 75 microM dose of quercetin was found to be effective as evidenced by decreased lipid peroxidation. To evaluate the protective potential of quercetin against genotoxic effects of nicotine we used comet and micronucleus assays, which are valid parameters to assess genetic damage. In addition, biochemical changes including lipid peroxidation and antioxidant status were assessed. There were significant increases in the levels of lipid peroxidation, comet parameters and micronuclei frequencies, followed by decrease in the endogenous antioxidant status, in nicotine-treated lymphocytes, which were brought back to near normal by quercetin or NAC treatment. The protective effect of quercetin against nicotine toxicity was comparable to that of NAC. These findings suggest that quercetin can be as effective as NAC in protecting rat peripheral lymphocytes against nicotine-induced cellular and DNA damage.