Neurochemical transmission in the dorsal column nuclei

The transmitter chemistry of the dorsal column nuclei is reviewed, with special emphasis on the monosynaptic component of the dorsal column-medial lemniscal pathway. It is maintained that in this anatomically addressed system concerned mainly with fast, secure sensory transmission, amino acids represent the predominant mechanism used for chemical relay of primary afferent impulses. The major excitatory primary afferent transmitter is most likely glutamic acid, whereas gamma-aminobutyric acid (GABA) fulfills adequately the role of transmitter of recurrent, postsynaptic and presynaptic inhibition. Recent immunohistochemical and physiological evidence indicates that 5-hydroxytryptamine, originating mainly from neurons of the raphé nuclei, plays a modulatory role in dorsal column transmission of innocuous sensory information. The basic synaptic elements involved in transmission across this relay, along with their corresponding chemical identities, are presented in the form of a speculative model.     

The effect of raphe nuclei lesions on the rat ovarian cycle

The effects of lesions of the median raphe or dorsal raphe nuclei on ovarian cycle were studied in rats. Lesions involving raphe nuclei decreased forebrain 5-HT and 5-hydroxyindole acid (5-HIAA) concentrations. Rats with lesions of the raphe showed prolonged estrous phase as well as an increase in both the eosinophilic index and karyopycnotic index of the vaginal smears. Histological examinations revealed that lesions of both the dorsal and median raphe produced marked increase in the number of maturing and mature follicles as well as an increase in corpora lutea. The increase in uterine weight was also observed. Present results indicate that lesions of the ascending 5-HT neurons stimulate ovulation and cause an increase in the estrogenic activity. Thus, the 5-HT neurons of the raphe nuclei seem to inhibit ovulation probably due to inhibiting of the hypothalamic releasing hormones.     

The effect of amino acid starvation on nucleoside uptake and RNA synthesis in Tetrahymena

The uptake of nucleosides and the synthesis of RNA in Tetrahymena thermophila were examined following amino acid starvation. Omission of leucine, phenylalanine, or arginine from the medium resulted in a rapid decrease in the incorporation of [3H]uridine into the acid-soluble pool and acid-insoluble material (RNA). Amino acid starvation inhibited the uptake of all ribo- and deoxyribonucleosides tested but did not affect the uptake of amino acids or glucose. In addition, under the conditions used, the omission of an amino acid did not result in a large decrease in amino acid incorporation into total protein. Treatment of cells with cycloheximide or emetine gave results similar to the effects of amino acid starvation, but in these experiments the inhibition of protein synthesis was essentially complete. Nucleotide pool sizes were also measured following amino acid starvation. ATP and UTP levels were essentially unchanged, but the dTTP pool size was decreased by 40%. The decrease in RNA synthesis in vivo in the absence of an essential amino acid was reflected in the endogenous RNA synthetic activity of isolated nuclei. However, when solubilized RNA polymerase activity was measured with calf thymus DNA as template, no significant difference was observed between control and amino acid-starved cells.     

Effects of succinylacetone on amino acid uptake in the rat kidney

Infants with hereditary tyrosinemia also have a renal Fanconi syndrome and excrete succinylacetone (SA). We have studied the effects of SA on rat renal tubular amino acid transport in vivo and in vitro using isolated renal tubules. Injection of SA produces increased clearance of several amino acids in the intact animal. In vitro SA causes a reversible inhibition of alpha-aminoisobutyric acid uptake, resulting from depressed low- and high-affinity transport systems. Addition of glutamate, succinate, or glucose, alone or in combination, did not restore transport. These observations suggest the usefulness of SA in the production of a physiologic animal model for the study of the human Fanconi syndrome.     

Effect of diabetes on levels and uptake of putative amino acid neurotransmitters in rat retina and retinal pigment epithelium

Free amino acid levels and high affinity uptake of glutamate, aspartate γ-aminobutyrate, glycine and taurine were studied in retina and retinal pigment epithelium of streptozotocin diabetic rats. Results show that experimental diabetes produces a generalized fall in the content of free amino acids in both retina and retinal pigment epithelium. With regard to the high affinity uptake, in the two tissues of diabetic animals showed decreased aspartate uptake, enhanced taurine and γ-aminobutyrate uptake, whereas that of glycine and glutamate was unchanged. These results might suggest that diabetes causes alterations of specific amino acid transport systems and/or alterations of some cell populations.     

The effect of caffeine on some mouse brain free amino acid levels

Changes in free amino acids were examined in the central nervous system of mice treated with caffeine for three weeks. Caffeine was administered in the drinking water, and at the end of three weeks the level of caffeine in the cerebral cortex was 113±19 g/g. When amino acid levels in cerebral hemispheres, midbrain, pons and medulla, and cerebellum were measured a significant increase in glutamine levels was found in all four regions. Glycine, alanine, serine, threonine, and GABA were significantly reduced in some regions. Caffeine appears to alter some of the metabolic or transport processes regulating amino acid pools in the brain. The decrease of GABA found in pons and medulla may contribute to the observed increase in reflex excitability after caffeine.Special issue dedicated to Dr. Elling Kvamme     

The effects of two anticonvulsants on amino acid levels in the developing rat cerebellum

Two anticonvulsants were administered pre- and postnatally to determine their effects on putative amino acid neurotransmitter levels in the rat cerebellum. The amino acids were quantitated using precolumn fluorescence derivatization and reverse-phase high performance liquid chromatography at various postnatal intervals. Treatment with clonazepam produced an initial depression in levels of most of the amino acids analyised. By three weeks postnatal all the amino acids, with the exception of GABA, had returned to control levels. GABA levels were still depressed five weeks after the cessation of treatment. Phenobarbital treatment produced an initial elevation in the level of GABA. At three weeks postnatal, both GABA and glutamate levels were elevated and remained so at eight weeks postnatal. In conclusion, the data demonstrated that each anticonvulsant produced unique, acute and chronic alterations in the levels of the cerebellar amino acids.     

The effect of lactogenic hormones on protein synthesis and amino acid uptake in rat mammary acinar cell culture at various physiological stages

• 1.1. The activities of protein synthesis and amino acid uptake at various physiological stages were determined by the incorporation of radioactive materials ([³H]-lysine, [¹⁴C]-cycloleucine) in rat mammary epithelial cell cultures. The activity of protein synthesis and amino acid uptake was higher in early lactation than in virgin, pregnant and late lactation stages.
• 2.2. Lactogenic hormones (prolactin, hydrocortisone and insulin) treatment related with mammary growth and differentiation increased the activities of protein synthesis and amino acid uptake. But increase of these activities was different at each physiological stage.
• 3.3. The effect of prolactin and hydrocortisone on the activities were greater in virgin, pregnant and late lactation than in early lactation. And effect of insulin was greater in pregnant and early lactation than in virgin and weanling.

     

Free amino acid levels in undernourished developing rat brain

Free amino acid levels in the brains of young ones born to mothers fed a 20% protein diet ad libitum (well nourished), 7.5% protein diet ad libitum (protein restricted) and a 20% protein diet in restricted amounts (pair-fed) were investigated during brain development in the present study. The dietary protein was obtained from a cereal-legume mixture. Protein restricted animals showed increases in the levels of taurine, glycine and glutamic acid and decreases in the concentrations of methionine, leucine, isoleucine, and GABA. The pair-fed animal showed increases only in glutamic acid and glycine and a decrease only in the levels of GABA. The significance of these observations is discussed.     

Cortical modulation of dorsal column nuclei: A computational study

We present a computational study aimed at exploring the sensorimotor cortex modulation of the behaviour of dorsal column nuclei, specifically the impact of synaptic parameters, during both sleep and waking conditions. On the basis of the circuit proposed by Canedo et al. (2000), we have developed realistic computational models that have been tested with simultaneous electrocorticographic as well as intracellular cuneate recordings performed in anaesthetized cats. The results show that, (1) under sleep conditions, the model can block the transmission of afferent sensory information and, (2) operations expected during wakefulness, such as filtering and facilitation, can be performed if synaptic parameters are appropriately tuned. Action Editor: Steve Redman