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.

Brainstem motor neuron dysmorphology and excitatory/inhibitory imbalance in an animal model of autism

“…However, there was difference in the number of brainstem LMNs examined in this study. It should be noted that the neuronal estimates provided in this study are consistent with previous reports [32]. The reason VPA exposure does not impact the number of oropharyngeal LMNs is unclear, but it appears that LMNs exhibit some degree of developmental protection.…”

“…This imbalance might lead to increased muscle tone or spasticity of tongue, pharyngeal, laryngeal and esophageal muscles and impaired swallowing, reduced caloric intake and poor weight gain. Furthermore, elevated glutamate may result in an excitotoxic environment further impacting LMN function [32]. HDAC inhibition is known to impact proliferation and differentiation of brainstem neurons [41].…”