Vol 76, No 4 (2017)
Original article
Published online: 2017-05-30
Neonatal exposure to monosodium glutamate results in dysmorphology of orofacial lower motor neurons
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.
Keywords: brainstemfacialtrigeminalhypoglossalvagus
References
- 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.
- Arees EA, Mayer J. Monosodium glutamate-induced brain lesions: electron microscopic examination. Science. 1970; 170(3957): 549–550.
- 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.
- 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.
- 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.
- 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.
- Curtis DR, Phillis JW, Watkin JC. Chemical excitation of spinal neurones. Nature. 1959; 183(4661): 611–613.
- Everly JL. Light microscopic examination of MSG-induced lesions in the brain of fetal and neonatal rats. Anat Rec. 1971; 169: 312.
- 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.
- 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.
- Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J neurochem. 1984; 42(1): 1–11.
- 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.
- Goldsmith PC. Neuroglial responses to elevated glutamate in the medial basal hypothalamus of the infant mouse. J Nutr. 2000; 130(4S Suppl): 1032S–1038S.
- 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.
- 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.
- Harris AJ. Critical periods in the development of motoneurons. Rev Neurol (Paris). 1988; 144(11): 643–647.
- 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.
- 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.
- Hattox AM, Priest CA, Keller A. Functional circuitry involved in the regulation of whisker movements. J Comp Neurol. 2002; 442(3): 266–276.
- 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.
- Hinrichsen CF, Watson CD. Brain stem projections to the facial nucleus of the rat. Brain Behav Evol. 1983; 22(2-3): 153–163.
- 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.
- 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.
- Kalb RG. Regulation of motor neuron dendrite growth by NMDA receptor activation. Development. 1994; 120(11): 3063–3071.
- 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.
- 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.
- Kulesza RJ. Cytoarchitecture of the human superior olivary complex: medial and lateral superior olive. Hear Res. 2007; 225(1-2): 80–90.
- 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.
- Kulesza RJ, Lukose R, Stevens LV. Malformation of the human superior olive in autistic spectrum disorders. Brain Res. 2011; 1367: 360–371.
- 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.
- Mattson MP. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008; 1144: 97–112.
- McCall A, Glaeser BS, Millington W, et al. Monosodium glutamate neurotoxicity, hyperosmolarity, and blood-brain barrier dysfunction. Neurobehav Toxicol. 1979; 1(4): 279–283.
- 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.
- Ndountse LT, Chan HM. Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity. Toxicol Lett. 2009; 184(1): 50–55.
- 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.
- Patel M, Day BJ, Crapo JD, et al. Requirement for superoxide in excitotoxic cell death. Neuron. 1996; 16(2): 345–355.
- 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.
- 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.
- 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.
- 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.
- Robinson MB, Coyle JT. Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. FASEB J. 1987; 1(6): 446–455.
- 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.
- Stafstrom CE. The role of glutamate transporters in developmental epilepsy: a concept in flux. Epilepsy Curr. 2004; 4(6): 243–244.
- 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.
- Travers JB. Oromotor Nuclei. In: George Paxinos, Oromotor Nuclei. Academic Press 2015: 223–245.
- 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.
- 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.
- Wagoner JL, Kulesza RJ. Topographical and cellular distribution of perineuronal nets in the human cochlear nucleus. Hear Res. 2009; 254(1-2): 42–53.
