Skip to main content

Pyridoxine Deficiency

Animal Model for CNS Serutonin and GABA Depletion

  • Protocol
Animal Models of Neurological Disease, II

Part of the book series: Neuromethods ((NM,volume 22))

Abstract

The term pyridoxine is generally used to refer to the group of naturally occurring pyridine derivatives represented by pyridoxine (pyridoxol), pyridoxal, and pyridoxamine, with similar physiological actions. They are referred to as vitamin B6 vitamers. Pyridoxine is used synonymously with vitamin B6. Pyridoxal phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over 100 known pyridoxal 5′-phosphate-dependent reactions, most of which are involved in the metabolism of various amino acids. Vitamin B6 plays a crucial role in the functioning of the nervous system. The putative neurotransmitters dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5HT), γ-aminobutyric acid (GABA), and taurine, as well as the sphingolipids and polyamines, are synthesized by PLP-dependent enzymes. There is considerable variation in the affinities of various apoenzymes for PLP. In view of this, during progressive pyridoxine deficiency, the PLP-dependent enzymes are decreased to various extents, from no decrease to almost a complete depletion. The decreases in the activities of glutamic acid and 5-hydroxytryptophan decarboxylases during pyridoxine deficiency result in the reduction of the concentrations of the neurotransmitters GABA and 5HT.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ando-Yamamoto M., Hayashi H., Taguchi Y., Fukui H., Watanabe T., and Wada H. (1986) at]Demonstration of immunohistochemical and immunochemical cross-reactivity of L-histidine and L-DOPA decarboxylases using antibodies against the two enzymes. Biochem. Biophys. Res. Commun. 141, 306–312.

    Article  PubMed  CAS  Google Scholar 

  • Bing R. F, Briggs R. S. J., Burden A. C., Russel G. I., Swales J. D., and Thurston H. (1980) Reversible hypertension and hypothyroidism. Clin. Endocrinol. 13, 339–342.

    Article  CAS  Google Scholar 

  • Brayshaw N. D. and Brayshaw D. D. (1986) Thyroid hypofunction in premenstrual syndrome (letter). N. Engl. J. Med. 315, 1486,1487.

    Google Scholar 

  • Brodie B. B., Costa E., Dlalac A., Neff N. H., and Smookler H. H. (1966) Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J. Phamacol. Exp. Ther. 154, 493–498.

    CAS  Google Scholar 

  • Brophy M. H. and Siiteri P. K. (1975) Pyridoxal phosphate and hypertensive disorders of pregnancy. Am. J. Obstet. Gynecol. 121, 1075–1079.

    PubMed  CAS  Google Scholar 

  • Brown P. M., Bacchus R., Sachs L., Sonsken P. H., and Wheeler M. (1979) Bromocriptine suppression of TRH stimulated prolactin and thyrotropin release and accompanying inhibition of bromocriptine induced growth hormone release by TRH in normal man. Clin. Endocrinol. 10, 481–488.

    Article  CAS  Google Scholar 

  • Brunello N., Barbaccia M. L., Chuang D. M., and Costa E. (1982) Down-regulation of 2 adrenergic receptors following repeated injections of desmethylimipramine; Permissive role of serotonergic axons. Neurupharmacology 21, 1145–1149.

    Article  CAS  Google Scholar 

  • Bunag R. D., Tomita T, and Sasaki S. (1983) Chronic sucrose ingestion induces mild hypertension and tachycardia in rats. Hypertension 5, 218–225.

    PubMed  CAS  Google Scholar 

  • Casper R. F., Patel-Christopher A., and Powell A. (1989) Thyrotropin and prolactin responses to TRH in premenstrual syndrome. J. Clin. Endocrinol Metab. 68, 608–612.

    Article  PubMed  CAS  Google Scholar 

  • Chen Y. F. and Ramirez V. D. (1981) Serotonin stimulates thyrotrophin-releasing hormone release from superfused rat hypothalami. Endocrinology 108, 2359–2366

    Article  PubMed  CAS  Google Scholar 

  • Christenson J. G., Dairman W., and Undenfriend S. (1972) On the identity of DOPA decarboxylase and 5-hydroxytryptophan. Proc. Natl. Acad. Sci. USA 69, 343–347.

    Article  PubMed  CAS  Google Scholar 

  • Dakshinamurti K. and Stephens M. C. (1969) Pyridoxine deficiency in the neonate rat. J. Neurochem. 16, 1515–1522.

    Article  PubMed  CAS  Google Scholar 

  • Dakshinamurti K., LeBlancq W. D., Herchl R., and Havlicek V. (1976) Nonparallel changes in brain monoamines of pyridoxine-deficient growing rats. Exp. Brain Res. 26, 355–366.

    Article  PubMed  CAS  Google Scholar 

  • Dakshinamurti K., Paulose C. S., Thliveris J. A., and Vriend J. (1985) Thyroid function in pyridoxine-deficient young rats. J. Endocrinol. 104, 339–344.

    Article  PubMed  CAS  Google Scholar 

  • Dakshinamurti K., Paulose C. S., and Vriend J. (1986) Hypothyroidism of hypothalamic origin in pyridoxine-deficient rats. J. Endocrinol. 109, 345–349.

    Article  PubMed  CAS  Google Scholar 

  • Dakshinamurti K., Paulose C. S., Viswanathan M., and Siow Y. L. (1988) Neuroendocrinology of pyridoxine deficiency. Neurosci. Behav. Rev. 12, 189–193.

    CAS  Google Scholar 

  • Delitala G., Rovasio P., and Lotti G. (1977) Suppression of TSH and PRL release by pyridoxine in chronic primary hypothyroidism. J. Clin. Endocrinol. Metab. 45, 1019–1022.

    Article  PubMed  CAS  Google Scholar 

  • Delitala G., Deville L., and Lotti G. (1980) Domperidone, an extracerebral inhibitor of dopamine receptors, stimulates thyrotropin and prolactin release in man. J. Clin. Endocrinol. Metab. 50, 1127–1130.

    Article  PubMed  CAS  Google Scholar 

  • Denner L. A. and Wu J.-Y. (1985) Two forms of rat brain glutamic acid decarboxylase differ in their dependence on free pyridoxal phosphate. J. Neurochem. 44, 957–965

    Article  PubMed  CAS  Google Scholar 

  • Falkner F. T. (1966) Human Development. W. B. Saunders, Philadelphia, pp. 123–149.

    Google Scholar 

  • Jordan D., Poncet C., Momex R., and Ponsin G. (1978) Participation of serotonin in thyrotropin release. 1. Evidence for the action of serotonin on thyrotropin releasing hormone release. Endocrinology 103, 414–419.

    Article  PubMed  CAS  Google Scholar 

  • Klieger J. A., Altshuler C. H., Krakow G., and Hollister C. (1969) Abnormal pyridoxine metabolism in toxemia of pregnancy. Ann. NY Acad. Sci. 166, 288–296.

    Article  PubMed  CAS  Google Scholar 

  • Kobinger W. and Pichler L. (1980) Relation between central sympatho-inhibitory and peripheral pre-and post-synaptic ol-adrenoreceptors as evaluated by different clonidine-like substances in rats. Naunyn-Schmiedberg’s Arch. Pharmacol. 315, 21–27.

    Article  CAS  Google Scholar 

  • Krulich L. (1979) Central neurotransmitters and the secretion of prolactin, GH, LH and TSH. Ann. Rev. Physiol., 41, 603–615.

    Article  CAS  Google Scholar 

  • Krulich L., MayField M. A., Steele M., McMillan B. A., McCann S. M., and Koenig J. I. (1982) Differential effects of pharmacological manipulations of central α1, and α2 adrenergic receptors on the secretion of TSH and GH in male rats. Endocrinology 110,796–804.

    Article  PubMed  CAS  Google Scholar 

  • Lipman K. M. (1990) Pyridoxine and thyroid function (letter). Am. J. Psychtr. 147, 372–373.

    CAS  Google Scholar 

  • Manheim P., Hallengren B., and Hansson B.-G. (1984) Plasma noradrenaline and blood pressure in hypothyroid patients: Effect of gradual thyroxine treatment. Clin. Endocrinol 20, 701–707.

    Article  Google Scholar 

  • Mannisto P. T. (1982) Central regulation of TRH secretion in rats: Methodological aspects, problems and some programs. Med. Biol. 61, 92–100.

    Google Scholar 

  • Noon J. P., Rice P.J., and Baldessarini R. J. (1978) Calcium leakage as a cause of the high resting tension in vascular smooth muscle from spontaneously hypertensive rat. Proc. Natl. Acad. Sci. USA 75, 1605–1607.

    Article  PubMed  CAS  Google Scholar 

  • Paulose C. S. and Dakshinamurti K. (1984) Enhancement of high affinity γ-aminobutyric acid receptor binding in cerebellum of pyridoxine-deficient rat. Neurosci. Lett. 48, 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Paulose C. S. and Dakshinamurti K. (1985) Effect of pyridoxine deficiency in young rats on high affiiity serotonin and dopamine receptors. J.Neurosci. Res. 12, 263–270.

    Article  Google Scholar 

  • Paulose C. S. and Dakshinamurti K. (1987) Chronic catheterization using vascular-accessport in rats: Blood sampling with minimal stress for plasma catecholamine determination. J. Neurosci. Methods 22, 141–146.

    Article  PubMed  CAS  Google Scholar 

  • Paulose C. S., Dakshinamurti K., Packer C. S., and Stephens N. L. (1988) Sympathetic stimulation and hypertension in the pyridoxine-deficient rat. Hypertension 11, 387–391.

    PubMed  CAS  Google Scholar 

  • Prelock J. P. (1984) Pineal gland function in mammals Endocrinol. Reu. 5, 282–308.

    Article  Google Scholar 

  • Rahman M. K., Nagatsu T., and Kato T. (1981) Aromatic L-amino acid decarboxylase activity in central and peripheral tissues and serum of rats with L-DOPA and L-5-hydroxytryptophan as substrates. Biochem. Pharmacol. 30, 645–649.

    Article  PubMed  CAS  Google Scholar 

  • Rahman M. K., Nagatsu T., Sakurai T., Hori S., Abe M., and Matsuda M. (1982) Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn. J. Pharnmol. 32, 803–811.

    Article  CAS  Google Scholar 

  • Rapp J. P., Nghiem C. X., and Onwochei M. D. (1986) Aortic calcium uptake and efflux in spontaneously hypertensive and inbred DahI rats. J. Hypertens. 4, 493–499.

    Article  PubMed  CAS  Google Scholar 

  • Rappaport A., Strutz F., and Guicheney P. (1985) Regulation of central alpha-adrenoreceptors by serotonergic denervations. Brain Res. 344, 158–161.

    Article  PubMed  CAS  Google Scholar 

  • Ruth R. E. and Morgan D. G. (1986) Dietary pyridoxine and susceptibility to limbic motor seizures in rats. Exp. Neural. 94, 441–448.

    Article  CAS  Google Scholar 

  • Saito J., Ito K., and Saruta T. (1983) Hypothyroidism as a cause of hypertension. Hypertension 5, 552–559.

    Google Scholar 

  • Sharma S. K. and Dakshinamurti K. (1992) Seizure activity in pyridoxine-deficient adult rats. Epilipsia, in press.

    Google Scholar 

  • Sims K. L., Davis G. A., and Bloom F. E. (1973) Activities of 3,4-dihydroxy-L-phenylalanine and 5-hydroxy tryptophan decarboxylases in rat brain: Assay characteristics and distribution. J. Neurochem. 20, 449–464.

    Article  PubMed  CAS  Google Scholar 

  • Siow Y. L. and Dakshinamurti K. (1985) Effect of pyridoxine deficiency on aromatic L-amino acid decarboxylase in adult rat brain. Exp. Brain Res 59, 575–581.

    Article  PubMed  CAS  Google Scholar 

  • Siow Y. L. and Dakshinamurti K. (1986) Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridoxine and l-methyl 4-phenylpyridinium on aromatic L-amino acid decarboxylase in rat brain. Biochem. Pharmaol. 35, 2640,264l.

    Google Scholar 

  • Siow Y. L. and Dakshinamurti K. (1990) Purification of DQPA decarboxylase from bovine striatum. Mol. Cell. Biochem. 94, 121–131.

    Article  CAS  Google Scholar 

  • Smith A. R. and Kappers J. A. (1975) Effect of pinealectomy, gonadectomy, pCPA and pineal extracts on the rat parvocellular neurosecretory hypothalamic system: A fluorescence histochemical investigation. Brain Res. 86, 353–371.

    Article  PubMed  CAS  Google Scholar 

  • Smyth G. A., Bradshaw J. E., Cai W. Y., and Symons R. G. (1982) Hypothalamic serotonergic stimulation of thyrotropin secretion and related brain-hormone and drug interactions in the rat. Endocrinology 111, 1181–1191.

    Article  Google Scholar 

  • Sourkes T. L. (1972) Influence of specific nutrients on catecholamine synthesis and metabolism. Pharmacol. Rev. 24, 349–359.

    PubMed  CAS  Google Scholar 

  • Stephens M. C., Havlicek V., and Dakshinamurti K. (1971) Fyridoxine deficiency and the development of CNS in the rat. J. Neurochem. 18, 2407–2416.

    Article  PubMed  CAS  Google Scholar 

  • Stewart J. W., Harrison W., and Quitkin F. (1984) Low B6 levels in depressed outpatients. Biol. Psychiatr. 19, 613–616.

    CAS  Google Scholar 

  • Viswanathan M., Siow Y. L., Paulose C. S., and Dakshinamurti K. (1988) Pineal indoleamine metabolism in pyridoxine-deficient rats. Brain Res. 473, 37–42.

    Article  PubMed  CAS  Google Scholar 

  • Viswanathan M., Paulose C. S., Lal K. J., Sharma S. K., and Dakshinamurti K. (1990) Alterations in brainstem α adrenoreceptor activity in pyridoxinedeficient rat model of hypertension. Neurosci. Lett. 111, 201–205.

    Article  PubMed  CAS  Google Scholar 

  • Viswanathan M., Bose R., and Dakshinamurti K. (1991) Increased calcium influx in caudal attery of rats made hypertensive with pyridoxine deficiency. Am. J. Hypertension, 4, 252–255.

    CAS  Google Scholar 

  • Wada K, Taketoshi M., Imamura I. Tanaka T., Horio Y., Taguchi Y., and Fukui H. (1990) Mammalian histidine decarboxylase and DOPA decarboxylase. Ann. NY Acad. Sci. 585, 145–161.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1992 The Humana Press Inc

About this protocol

Cite this protocol

Dakshinamurti, K., Sharma, S.K., Lal, K.J. (1992). Pyridoxine Deficiency. In: Boulton, A.A., Baker, G.B., Butterworth, R.F. (eds) Animal Models of Neurological Disease, II. Neuromethods, vol 22. Humana Press. https://doi.org/10.1385/0-89603-211-6:299

Download citation

  • DOI: https://doi.org/10.1385/0-89603-211-6:299

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-211-8

  • Online ISBN: 978-1-59259-627-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics