Central Nervous System Circuitries Underlying Two Types of Peripheral Autonomic Nervous System Disorders~!2008-04-24~!2008-09-26~!2008-12-05~!

Abstract

Abstract:The assessment of circulating neurotransmitters: noradrenaline, adrenaline, dopamine, platelet serotonin, plasma serotonin and plasma tryptophan before and after many types of stressor agents and neuropharmacological drugs carried out over the last thirty years allowed us to accumulate information dealing with the central nervous system (CNS) versus the peripheral autonomic nervous system (ANS) interactions in healthy as well as diseased mammals. Furthermore, the accurate knowledge about the CNS circuitry disorders which underlie both the CNS and peripheral clinical syndromes, has allowed us to prescribe successful neuropharmacological therapeutical strategies for many types of illnesses. In addition, the demonstration that the clinical improvement was always paralleled by the normalization of the neurochemical, hormonal, immunological and clinical profiles affords strong support to our point of view. According to all the above, the authors postulate the existence of two types of diseases: type A and Type N, which are underlain by two opposite CNS + ANS disorders. Type A diseases should be associated with the "uncoping stress" syndrome and are underlain by hyperactivity of the adrenocortical glands plus the CNS disorder characterized by the predominance of the C1(adrenergic) + DR(serotonergic) axis over the A5(noradrenergic) + MR(serotonergic) binomial, whereas the type N diseases depends on the opposite profile: "endogenous depression" syndrome. Finally, we quoted exhaustive evidence showing that the well known fading of both the A6(noradrenergic) + C1(adrenergic) CNS nuclei activity occurring during aging is responsible for the ANS + CNS disorder which is similar to that underlying psychosis, Alzheimer, post-traumatic stress disorder and deficit-attention hyperactive disorder.

Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

“…[16][17][18] In addition, both sympathetic branches of the peripheral ANS depend on the A 5 pontomedullary nucleus that releases noradrenaline (NA) 19 and the C 1 medullary nuclei which secrete adrenaline (Ad). [20][21][22][23][24] Furthermore, both CNS nuclei interchange direct inhibitory axons whose neurotransmitters act at post-synaptic alpha-2 receptors, which crowd both nuclei. [18][19][20][21][22][23][24][25] Finally, experimental evidence has demonstrated that secretion of both peripheral hormones (insulin and glucagon) would depend on the interaction between two opposite neuroendocrine circuits.…”

“…[20][21][22][23][24] Furthermore, both CNS nuclei interchange direct inhibitory axons whose neurotransmitters act at post-synaptic alpha-2 receptors, which crowd both nuclei. [18][19][20][21][22][23][24][25] Finally, experimental evidence has demonstrated that secretion of both peripheral hormones (insulin and glucagon) would depend on the interaction between two opposite neuroendocrine circuits. According to the above, we decided to investigate the effect of amantadine, a glutamic acid (N-methyl-D-aspartate [NMDA]) antagonist, which inhibits the C 1 (Ad) but not the A 5 (NA) nuclei, and provokes absolute reduction of plasma adrenaline concentration when administered to normal subjects during fasting conditions.…”

“…With respect to this, experimental evidences obtained from our laboratory, demonstrated that a small dose of amantadine (administered without glucose) provokes absolute minimization of the adrenaline plasma concentration. 24,29 In addition to all the above, some other factors should be considered in order to understand the ability by amantadine to annul the glucagon-induced excitatory effect at the CNS C 1 (Ad) + peripheral adrenal sympathetic axis, which would explain its insulinogenic + hypoglycemic effects. For instance, the drug was able to provoke maximal reduction of both plasma serotonin and platelet serotonin concentration.…”

“…24,49 The above CNS A 5 (NA) versus C 1 (Ad) predominance which redounded in the peripheral neural sympathetic plus beta-cells hyperactivity merits some additional comments. With respect to this, it should be known that sympathetic nerves innervate and excite alpha-cells by acting at alpha-2 receptors but not beta-cells.…”

“…This postulation receives definite support from overwhelming evidence quoted in several review articles and books. 24,29,41,51,52 Summarizing all the above, it is possible to postulate that the hypoglycemic + hypoglucagonemic + insulinogenic effects triggered by the addition of amantadine to an oral glucose load would depend of both peripheral plus central nervous system mechanisms. The former should be associated to the minimization of the alpha-cells + adrenal glands secretion whereas the latter should be associated with the inhibition of the C 1 (Ad) plus the disinhibition of the A 5 (NA), responsible for the peripheral adrenal sympathetic and neural sympathetic branches axis, respectively.…”