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Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

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Abstract

Wistar rat pups were administered either a high dose of lead acetate (400 μg lead/g body weight/day) or a low dose (100 μg lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.

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References

  • Annamma C, Desiraju T (1988) Deviations in brain development of F2 generational calorie undernutrition and scope of their prevention by rehabilitation: imbalances in the levels of noradrenaline, dopamine and serotonin in different brain regions. Biogenic Amines 5: 32–337

    Google Scholar 

  • Bondy SC, Anderson CL, Harrington ME, Prasad KN (1979a) The effects of organic and inorganic lead and mercury on neurotransmitter high-affinity transport and release mechanisms. Environ Res 19: 102–111

    PubMed  Google Scholar 

  • Bondy SC, Harrington ME, Anderson CL, Prasad KN (1979b) The effect of low concentration of an organic lead concentration on the transport and release of putative transmitters. Toxicol Lett 3: 35–41

    Google Scholar 

  • Campbell AMC, Williams ER, Barltrop D (1970) Motor neurone disease and exposure to lead. J Neurol Neurosurg Psychiatry 33: 877–885

    PubMed  Google Scholar 

  • Caspers ML (1982) Inhibition by lead of phenylethanolamine N-methyl transferace. Biochem Pharmacol 31: 1985–1988

    PubMed  Google Scholar 

  • Cox RH, Perhach JL (1973) A sensitive, rapid and simple method for the simultaneous spectrophotofluorometric determination of noradrenaline, dopamine, serotonin and 5-hydroxyindole acetic acid in discrete areas of brain. J Neurochem 20: 1777–1780

    PubMed  Google Scholar 

  • Desiraju T (1966) Role of potassium and calcium in the turnover of acetylcholine. Q J Exp Physiol 51: 177–183

    Google Scholar 

  • Dubas TC, Hrdina PD (1978) Behavioural and Neurochemical consequences of neonatal exposure to lead in rats. J Environ Pathol Toxicol 2: 473–484

    Google Scholar 

  • Dubas TC, Stevenson A, Singhal RL, Hrdina PD (1978) Regional alterations of brain biogenic amines in young rats following chronic lead exposure. Toxicology 9: 185–190

    PubMed  Google Scholar 

  • Glowinsky J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. The disposition of (3H) norepinephrine, (3H) dopamine and (3H) dopa in various regions of the brain. J Neurochem 13: 655–669

    PubMed  Google Scholar 

  • Golter M, Michaelson IA (1975) Growth, behaviour, and brain catecholamines in lead-exposed neonatal rats: a reappraisal. Science 187: 359–361

    PubMed  Google Scholar 

  • Govoni S, Montefusco O, Spano PF, Trabucchi M (1978) Dopamine synthesis and serum prolactin release in the rat. Toxicol Lett 2: 333–337

    Google Scholar 

  • Govoni S, Memo M, Lucchi L, Spano PF, Trabucchi M (1979) Chronic lead treatment differentially affects dopamine synthesis in various rat brain areas. Toxicology 12: 343–349

    PubMed  Google Scholar 

  • Govoni S, Lucchi L, Battaini F, Spano PF, Trabucchi M (1984) Chronic lead treatment affects dopaminergic control of prolactin secretion in rat pituitary. Toxicol Lett 20: 237–241

    PubMed  Google Scholar 

  • Grant LD, Kimmel CA, Martinez-Vargas CM, West GL (1976) Assessment of developmental toxicity associated with chronic lead exposure. Environ Health Perspect 17: 290

    Google Scholar 

  • Gundappa G, Desiraju T (1988) Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex. Brain Res 456: 205–223

    PubMed  Google Scholar 

  • Jason KM, Kellogg CK (1977) Lead effects on behavioural and neurochemical development in rats. Fed Proc 36: 1008 (Abstract 3887)

    Google Scholar 

  • Jason KM, Kellogg CK (1981) Neonatal lead exposure: effects on development of behaviour and striatal dopamine neurons. Pharmacol Biochem Behav 15: 641–649

    PubMed  Google Scholar 

  • Krall AR, Pesavento C, Harmon SJ, Packer III RM (1972) Elevation of norepinephrine levels and inhibition of mitochondrial oxidative phosphorylation in cerebellum of lead-intoxicated suckling rats. Fed Proc 31: 665

    Google Scholar 

  • Krigman MR, Mushak P, Bouldin TW (1977) An appraisal of rodent model of lead encephalopathy. In: Roizin L, Shiraki H (eds) Neurotoxicology. Raven Press, New York, pp 299–302

    Google Scholar 

  • Lin-Fu JS (1972) Undue absorption of lead among children. A new look at an old problem. New Engl J Med 286: 702–710

    PubMed  Google Scholar 

  • Lowry CH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275

    PubMed  Google Scholar 

  • Lucchi L, Memo M, Airaghi ML, Spano PF, Trabucchi M (1981) Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain areas. Brain Res 213: 397–404

    PubMed  Google Scholar 

  • Mascarenhas C, Rajanna B, Gundappa G, Annamma C, Desiraju T (1986) Experimental findings on the impact of early undernutrition on brain development and effects of subsequent rehabilitation. In: Kochupillai N, Karmarkar MG, Ramalingaswami V (eds) Iodine nutrition, thyroxine and brain development. Tata McGraw-Hill, New Delhi, pp 191–199

    Google Scholar 

  • Memo M, Lucchi L, Spano PF, Trabucchi M (1981) Dose-dependent and reversible effects of lead on rat dopaminergic system. Life Sci 28: 795–799

    PubMed  Google Scholar 

  • Murozomi M, Chow TJ, Patterson LC (1969) Geo-chim Cosmochim Acta 33: 1247 [cited in Graef JW (1979) Clinical aspects of lead poisoning. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. Elsevier Press, Amsterdam, Vol 36; pp 1–3]

    Google Scholar 

  • Nathanson JA, Bloom FE (1975) Lead-induced inhibition of brain adenyl cyclase. Nature 255: 419–420

    PubMed  Google Scholar 

  • Niklowitz WJ, Mandybur TI (1975) Neurofibrillary changes following childhood lead encephalopathy. J Neuropathol Exp Neurol 34: 445–455

    PubMed  Google Scholar 

  • Patel AJ, Michealson IA, Cremer JE, Balazs R (1974) The metabolism of14C-glucose by the brains of suckling rats intoxicated with inorganic lead. J Neurochem 22: 581–590

    PubMed  Google Scholar 

  • Peipho RW, Ryan CF, Lacz JP (1976) The effects of chronic lead intoxication on the gamma-amino-butyric acid content of the rat CNS. Pharmacology 18: 125–131

    Google Scholar 

  • Pentschew A, Garro F (1966) Lead encephalomyelopathy of the suckling rat and its implications on the prophyrinopathic nervous disease. Acta Neuropathol 6: 266–278

    PubMed  Google Scholar 

  • Rajanna B, Mascarenhas C, Desiraju T (1987) Deviations in brain development due to caloric undernutrition and scope of their prevention by rehabilitation: alterations in the power spectra of the EEG of areas of the neocortex and limbic system. Dev Brain Res 37: 97–113

    Google Scholar 

  • Ramsay PB, Krigman MR, Morell P (1980) Developmental studies of the uptake of choline, GABA and dopamine by crude synaptosomal preparations after in vivo or in vitro lead treatment. Brain Res 187: 383–402

    PubMed  Google Scholar 

  • Sadasivudu B, Murthy ChRK (1978) Effects of ammonia on monoamine oxides and enzymes of GABA metabolism in mouse brain. Arch Int Physiol Biochim 86: 67–82

    PubMed  Google Scholar 

  • Sauerhoff MW, Michealson IA (1973) hyperactivity and brain catecholamines in lead exposed developing rats. Science 182: 1022–1024

    PubMed  Google Scholar 

  • Schreir HA, Sherry N, Shanghnessy E (1977) Lead poisoning and brain tumors in children: a report of two cases. Ann Neurol 1: 599

    PubMed  Google Scholar 

  • Shellenberger MK, Gordon JH (1971) A rapid, simplified procedure for simultaneous assay of norepinephrine, dopamine and 5-hydroxytryptamine from discrete brain areas. Anal Biochem 39: 356–372

    PubMed  Google Scholar 

  • Silbergeld EK, Goldberg AM (1973) A lead induced behavioural disorder. Life Sci 13: 1275–1283

    Google Scholar 

  • Silbergeld EK, Fales JT, Goldberg AM (1974) Evidence for a junctional effect of lead on neuromuscular function. Nature 247: 49–50

    PubMed  Google Scholar 

  • Silbergeld EK, Miller LP, Kennedy S, Eng N (1979) Lead, GABA and seizures: effects of sub-encephalopathic lead exposure on seizure sensitivity and GABAergic function. Environ Res 19: 371–382

    PubMed  Google Scholar 

  • Silbergeld EK, Hruska RE, Miller LP, Nancy Eng (1980) Effects of lead in vivo and in vitro on GABAergic neurochemistry. J Neurochem 36(6): 1712–1718

    Google Scholar 

  • Snedecor GW, Cochran WG (1967) Statistical methods. Oxford and IBH Publ, New Delhi

    Google Scholar 

  • Snyder SH (1984) Drug and neurotransmitter receptors in the brain. Science 224: 22–31

    PubMed  Google Scholar 

  • Snyder SH (1989) Drug and neurotransmitter receptors. New perspectives with clinical relevance. JAMA 261: 3126–3129

    PubMed  Google Scholar 

  • Sobotka TJ, Cook M (1974) Postnatal lead acetate exposure in rats: possible relationship to minimal brain dysfunction. Am J Ment Dis 79: 5–9

    Google Scholar 

  • Sobotka TJ, Brodie RE, Cook MP (1975) Psychophysiologic effects of early lead exposure. Toxicology 5: 175–191

    PubMed  Google Scholar 

  • Toews AD, Krigman MR, Thomas DJ, Morell P (1980) Effect of inorganic lead exposure on myelination in the rat. Neurochem Res 5: 605–615

    PubMed  Google Scholar 

  • Toews AD, Blaker WD, Thomas DJ, Gaynor JJ, Krigman MR, Mushak P, Morell P (1983) Myelin deficits produced by early postnatal exposure to inorganic lead or triethyltin are persistent. J Neurochem 41: 816–822

    PubMed  Google Scholar 

  • Unni L, Caspers ML (1985) Inhibition of bovine brain monoamine oxidase by lead. Biochem Pharmacol 34: 2563–2566

    PubMed  Google Scholar 

  • Verhaart WJC (1942) Lead encephalopathy simulating diffuse sclerosis in a Chinese infant. Am J Dis Child 38: 1246

    Google Scholar 

  • Wapnir RA, Exeni RS, McVicar M, Lifschitz E (1977) Experimental lead poisoning and intestinal transport of glucose, amino acids and sodium. Pediatr Res 11: 153–157

    PubMed  Google Scholar 

  • Wince LC, Donovan CA, Azzaro AJ (1980) Alterations in the biochemical properties of central dopamine synapses following chronic postnatal PbCO3 exposure. J Pharmacol Exp Ther 214: 642–650

    PubMed  Google Scholar 

  • Winder C, Kitchen I (1984) Lead neurotoxicity: a review of the biochemical, neurochemical and drug induced behavioural evidence. Prog Neurobiol 22: 59–87

    PubMed  Google Scholar 

Download references

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Kumar, M.V.S., Desiraju, T. Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development. Arch Toxicol 64, 305–314 (1990). https://doi.org/10.1007/BF01972991

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  • DOI: https://doi.org/10.1007/BF01972991

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