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Vol 76, No 4 (2017)
Original article
Submitted: 2016-02-16
Accepted: 2016-03-14
Published online: 2017-05-30
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Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons

L. Foran1, C. Kupelian1, S. Laroia2, J. Esper2, R. J. Kulesza1
DOI: 10.5603/FM.a2017.0052
·
Pubmed: 28612917
·
Folia Morphol 2017;76(4):582-589.
Affiliations
  1. Department of Anatomy, Lake Erie College of Osteopathic Medicine, Erie, PA, United States
  2. University of Pittsburgh Medical Center – Hamot, Neuroscience Institute, Erie, PA,, United States

open access

Vol 76, No 4 (2017)
ORIGINAL ARTICLES
Submitted: 2016-02-16
Accepted: 2016-03-14
Published online: 2017-05-30

Abstract

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavour enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterised by neuronal loss and neuroendocrine abnormalities. However, the brainstem effects of neonatal MSG exposure have not been investigated. It is therefore hypothesized that MSG exposure during the early postnatal period would impact brainstem lower motor neurons involved in feeding behaviour. The effect of neonatal MSG exposure on brainstem lower motor neurons was investigated by exposing rat pups to either 4 mg/g MSG or saline from postnatal day (P) 4 through 10. On P28, brains were preserved by vascular perfusion with fixative, frozen sectioned and stained for Nïssl substance. The number, size and shape of brainstem motor neurons were compared between MSG and saline-exposed animals. MSG exposure had no impact on the total number of neurons in the nuclei examined. However, MSG exposure was associated with a significant increase in the number of round somata in both the trigeminal and facial nuclei. Furthermore, MSG exposure resulted in significantly smaller neurons in all motor nuclei examined. These results suggest that neonatal exposure to MSG impacts the development of brainstem lower motor neurons which may impact feeding and swallowing behaviours in young animals.  

Abstract

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and is stored and released by both neurons and astrocytes. Despite the important role of glutamate as a neurotransmitter, high levels of extracellular glutamate can result in excitotoxicity and apoptosis. Monosodium glutamate (MSG) is a naturally occurring sodium salt of glutamic acid that is used as a flavour enhancer in many processed foods. Neonatal exposure to MSG has been shown to result in neurodegeneration in several forebrain regions, characterised by neuronal loss and neuroendocrine abnormalities. However, the brainstem effects of neonatal MSG exposure have not been investigated. It is therefore hypothesized that MSG exposure during the early postnatal period would impact brainstem lower motor neurons involved in feeding behaviour. The effect of neonatal MSG exposure on brainstem lower motor neurons was investigated by exposing rat pups to either 4 mg/g MSG or saline from postnatal day (P) 4 through 10. On P28, brains were preserved by vascular perfusion with fixative, frozen sectioned and stained for Nïssl substance. The number, size and shape of brainstem motor neurons were compared between MSG and saline-exposed animals. MSG exposure had no impact on the total number of neurons in the nuclei examined. However, MSG exposure was associated with a significant increase in the number of round somata in both the trigeminal and facial nuclei. Furthermore, MSG exposure resulted in significantly smaller neurons in all motor nuclei examined. These results suggest that neonatal exposure to MSG impacts the development of brainstem lower motor neurons which may impact feeding and swallowing behaviours in young animals.  

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Keywords

brainstem, facial, trigeminal, hypoglossal, vagus

About this article
Title

Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons

Journal

Folia Morphologica

Issue

Vol 76, No 4 (2017)

Article type

Original article

Pages

582-589

Published online

2017-05-30

Page views

1671

Article views/downloads

1558

DOI

10.5603/FM.a2017.0052

Pubmed

28612917

Bibliographic record

Folia Morphol 2017;76(4):582-589.

Keywords

brainstem
facial
trigeminal
hypoglossal
vagus

Authors

L. Foran
C. Kupelian
S. Laroia
J. Esper
R. J. Kulesza

References (48)
  1. Alloway KD, Smith JB, Beauchemin KJ. Quantitative analysis of the bilateral brainstem projections from the whisker and forepaw regions in rat primary motor cortex. J Comp Neurol. 2010; 518(22): 4546–4566.
    CrossRefPubMed
  2. Arees EA, Mayer J. Monosodium glutamate-induced brain lesions: electron microscopic examination. Science. 1970; 170(3957): 549–550.
    PubMed
  3. Bojanic VV, Bojanic Z, Najman S, et al. Diltiazem prevention of monosodium glutamate toxicity on hypothalamus in Wistar rats. Arch Oncol. 2004; 12: 19–20.
  4. Burde RM, Schainker B, Kayes J. Acute effect of oral and subcutaneous administration of monosodium glutamate on the arcuate nucleus of the hypothalamus in mice and rats. Nature. 1971; 233(5314): 58–60.
    PubMed
  5. Carricondo F, Bartolomé MV, Vicente-Torres MA, et al. Sensitivity to glutamate neurotoxicity in different developmental periods of the rat cochlea. Adv Otorhinolaryngol. 2002; 59: 91–95.
    PubMed
  6. Chaparro-Huerta V, Rivera-Cervantes MC, Torres-Mendoza BM, et al. Neuronal death and tumor necrosis factor-alpha response to glutamate-induced excitotoxicity in the cerebral cortex of neonatal rats. Neurosci Lett. 2002; 333(2): 95–98.
    PubMed
  7. Curtis DR, Phillis JW, Watkin JC. Chemical excitation of spinal neurones. Nature. 1959; 183(4661): 611–613.
    PubMed
  8. Everly JL. Light microscopic examination of MSG-induced lesions in the brain of fetal and neonatal rats. Anat Rec. 1971; 169: 312.
  9. Fan MMY, Raymond LA. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog Neurobiol. 2007; 81(5-6): 272–293.
    CrossRefPubMed
  10. Fay RA, Norgren R. Identification of rat brainstem multisynaptic connections to the oral motor nuclei in the rat using pseudorabies virus. II. Facial muscle motor systems. Brain Res Brain Res Rev. 1997; 25(3): 276–290.
    PubMed
  11. Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J neurochem. 1984; 42(1): 1–11.
    CrossRef
  12. Gill SS, Mueller RW, McGuire PF, et al. Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity. Toxicol Pathol. 2000; 28(2): 277–284.
    CrossRefPubMed
  13. Goldsmith PC. Neuroglial responses to elevated glutamate in the medial basal hypothalamus of the infant mouse. J Nutr. 2000; 130(4S Suppl): 1032S–1038S.
    PubMed
  14. González-Burgos I, Velázquez-Zamora DA, Beas-Zárate C. Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicity. Int J Dev Neurosci. 2009; 27(8): 741–745.
    CrossRefPubMed
  15. Gonzalez-Joekes J, Schreurs BG. Anatomical characterization of a rabbit cerebellar eyeblink premotor pathway using pseudorabies and identification of a local modulatory network in anterior interpositus. J Neurosci. 2012; 32(36): 12472–12487.
    CrossRefPubMed
  16. Harris AJ. Critical periods in the development of motoneurons. Rev Neurol (Paris). 1988; 144(11): 643–647.
    PubMed
  17. Hartley DM, Choi DW. Delayed rescue of N-methyl-D-aspartate receptor-mediated neuronal injury in cortical culture. J Pharmacol Exp Ther. 1989; 250(2): 752–758.
    PubMed
  18. Hashem HE, El-Din Safwat MD, Algaidi S. The effect of monosodium glutamate on the cerebellar cortex of male albino rats and the protective role of vitamin C (histological and immunohistochemical study). J Mol Histol. 2012; 43(2): 179–186.
    CrossRefPubMed
  19. Hattox AM, Priest CA, Keller A. Functional circuitry involved in the regulation of whisker movements. J Comp Neurol. 2002; 442(3): 266–276.
    PubMed
  20. Hayashi T. A physiological study of epileptic seizures following cortical stimulation in animals and its application to human clinics. Jpn J Physiol. 1952; 3: 46–64.
    CrossRef
  21. Hinrichsen CF, Watson CD. Brain stem projections to the facial nucleus of the rat. Brain Behav Evol. 1983; 22(2-3): 153–163.
    PubMed
  22. Holstege G, van Ham JJ, Tan J. Afferent projections to the orbicularis oculi motoneuronal cell group. An autoradiographical tracing study in the cat. Brain Res. 1986; 374(2): 306–320.
    PubMed
  23. Jung KH, Chu K, Lee ST, et al. Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition. Biochem Biophys Res Commun. 2009; 378(3): 507–512.
    CrossRefPubMed
  24. Kalb RG. Regulation of motor neuron dendrite growth by NMDA receptor activation. Development. 1994; 120(11): 3063–3071.
    PubMed
  25. Kawamura M, Azuma N, Kohsaka S. [Experimental studies on microphthalmos formation in neonatal rats treated with monosodium-L-glutamate]. Nippon Ganka Gakkai Zasshi. 1989; 93(5): 553–561.
    PubMed
  26. Kiss P, Tamas A, Lubics A, et al. Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate. Neurotox Res. 2005; 8(3-4): 235–244.
    PubMed
  27. Kulesza RJ. Cytoarchitecture of the human superior olivary complex: medial and lateral superior olive. Hear Res. 2007; 225(1-2): 80–90.
    CrossRefPubMed
  28. Kulesza RJ. Cytoarchitecture of the human superior olivary complex: nuclei of the trapezoid body and posterior tier. Hear Res. 2008; 241(1-2): 52–63.
    CrossRefPubMed
  29. Kulesza RJ, Lukose R, Stevens LV. Malformation of the human superior olive in autistic spectrum disorders. Brain Res. 2011; 1367: 360–371.
    CrossRefPubMed
  30. Li YQ, Takada M, Kaneko T, et al. Distribution of GABAergic and glycinergic premotor neurons projecting to the facial and hypoglossal nuclei in the rat. J Comp Neurol. 1997; 378(2): 283–294.
    PubMed
  31. Mattson MP. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008; 1144: 97–112.
    CrossRefPubMed
  32. McCall A, Glaeser BS, Millington W, et al. Monosodium glutamate neurotoxicity, hyperosmolarity, and blood-brain barrier dysfunction. Neurobehav Toxicol. 1979; 1(4): 279–283.
    PubMed
  33. Michaelis EK. Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol. 1998; 54(4): 369–415.
    PubMed
  34. Ndountse LT, Chan HM. Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity. Toxicol Lett. 2009; 184(1): 50–55.
    CrossRefPubMed
  35. Oser BL, Carson S, Vogin EE, et al. Oral and subcutaneous administration of monosodium glutamate to infant rodents and dogs. Nature. 1971; 229(5284): 411–413.
    PubMed
  36. Patel M, Day BJ, Crapo JD, et al. Requirement for superoxide in excitotoxic cell death. Neuron. 1996; 16(2): 345–355.
    PubMed
  37. Prastiwi D, Djunaidi A, Partadiredja G. High dosage of monosodium glutamate causes deficits of the motor coordination and the number of cerebellar Purkinje cells of rats. Hum Exp Toxicol. 2015; 34(11): 1171–1179.
    CrossRefPubMed
  38. Quines CB, Rosa SG, Da Rocha JT, et al. Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats. Life Sci. 2014; 107(1-2): 27–31.
    CrossRefPubMed
  39. Regan JW, Roeske WR, Ruth WH, et al. Reductions in retinal gamma-aminobutyric acid (GABA) content and in [3H]flunitrazepam binding after postnatal monosodium glutamate injections in rats. J Pharmacol Exp Ther. 1981; 218(3): 791–796.
    PubMed
  40. Rivera-Cervantes MC, Torres JS, Feria-Velasco A, et al. NMDA and AMPA receptor expression and cortical neuronal death are associated with p38 in glutamate-induced excitotoxicity in vivo. J Neurosci Res. 2004; 76(5): 678–687.
    CrossRefPubMed
  41. Robinson MB, Coyle JT. Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. FASEB J. 1987; 1(6): 446–455.
    PubMed
  42. Shah SA, Yoon GHo, Kim HO, et al. Vitamin C neuroprotection against dose-dependent glutamate-induced neurodegeneration in the postnatal brain. Neurochem Res. 2015; 40(5): 875–884.
    CrossRefPubMed
  43. Stafstrom CE. The role of glutamate transporters in developmental epilepsy: a concept in flux. Epilepsy Curr. 2004; 4(6): 243–244.
    CrossRefPubMed
  44. Takada M, Itoh K, Yasui Y, et al. Distribution of premotor neurons for orbicularis oculi motoneurons in the cat, with particular reference to possible pathways for blink reflex. Neurosci Lett. 1984; 50(1-3): 251–255.
    PubMed
  45. Travers JB. Oromotor Nuclei. In: George Paxinos, Oromotor Nuclei. Academic Press 2015: 223–245.
  46. Ureña-Guerrero ME, López-Pérez SJ, Beas-Zárate C. Neonatal monosodium glutamate treatment modifies glutamic acid decarboxylase activity during rat brain postnatal development. Neurochem Int. 2003; 42(4): 269–276.
    PubMed
  47. van Rijn CM, Marani E, Rietveld WJ. The neurotoxic effect of monosodium glutamate (MSG) on the retinal ganglion cells of the albino rat. Histol Histopathol. 1986; 1(3): 291–295.
    PubMed
  48. Wagoner JL, Kulesza RJ. Topographical and cellular distribution of perineuronal nets in the human cochlear nucleus. Hear Res. 2009; 254(1-2): 42–53.
    CrossRefPubMed

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