Monosodium glutamate ingestion during the development period reduces aggression mediated by the vagus nerve in a rat model of attention deficit-hyperactivity disorder

Abstract

We used an umami substance, monosodium glutamate (MSG), as a simple stimulant to clarify the mechanism of the formation of emotional behavior. A 60 mM MSG solution was fed to spontaneously hypertensive rats (SHR), used as a model of attention-deficit hyperactivity disorder, from postnatal day 25 for 5 weeks kept in isolation. Emotional behaviors (anxiety and aggression) were then assessed by the open-field test, cylinder test and social interaction test. MSG ingestion during the developmental period resulted in a significant reduction in aggressive behavior but had few effects on anxiety-like behavior. Several experiments were performed to identify the reason for the reduced aggression with MSG intake. Blood pressure in the MSG-treated SHR was comparable to that of the controls during development. Argyrophil III staining to detect the very early phase of neuronal damage revealed no evidence of injury by MSG in aggression-related brain areas. Assessment of plasma amino acids revealed that glutamate levels remained constant (∼80 μM) with MSG ingestion, except for a transient increase after fasting (∼700 μM). However, lactate dehydrogenase assay in an in vitro blood-brain barrier model showed that cell toxicity was not induced by indirect MSG application even at 700 μM, confirming that MSG ingestion caused minimal neuronal damage. Finally, vagotomy at the sub-diaphragmatic level before MSG ingestion blocked its effect on aggressive behavior in the isolated SHR. The data suggest that MSG ingestion during the developmental period can reduce aggressive behavior in an attention deficit-hyperactivity disorder model rat, mediated by gut-brain interaction.

Effects of Five Amino Acids (Serine, Alanine, Glutamate, Aspartate, and Tyrosine) on Mental Health in Healthy Office Workers: A Randomized, Double-Blind, Placebo-Controlled Exploratory Trial

“…Each amino acid contained in SAGAT has been reported to improve mental health problems or cognitive functions. We hypothesized that Tyr and Ser, which directly affect neurons [ 18 , 21 ], function as the main effects of SAGAT, and the other three amino acids promote their effects, because they have been reported to reduce fatigue or mental health-related behavior in animal model studies [ 23 , 24 , 25 ]. However, there was no research showing the combinational effects of these amino acids.…”

“…Third, previous reports showed that the ingestion of monosodium glutamate (MSG) indirectly induced behavioral changes through gut–brain interaction mediated by the vagus nerve in a rat with an attention deficit hyperactivity disorder [ 23 ], suggesting that the oral intake of Glu caused the interaction of the gut–brain axis. Furthermore, MSG supplementation is known to increase gastric acid secretion in patients with chronic gastritis [ 43 ], and the umami taste is the most potent taste stimulus for saliva secretion from the parotid gland [ 44 ].…”

“…Recently, the combination of Ser and eicosapentaenoic acid has been reported to be effective for pain relief in adults with low back and knee pain mediated by their neuroprotective function [ 22 ]. The ingestion of glutamate (Glu) during the developmental period reduced aggressive behavior in a model rat with an attention-deficit hyperactivity disorder, and this effect is mediated by gut–brain interaction [ 23 ]. Alanine (Ala) has been reported to modulate anxiety-like behavior in rats [ 24 ], and aspartate (Asp) is known to increase the contribution of oxidative metabolism in energy production and delay fatigue during exercise [ 25 ].…”

Vagotomy and the risk of mental disorders: A nationwide population‐based study

“…Former animal studies investigating vagotomy and behavioral changes in rodents have investigated anxiety-and depressive-like behavior, schizophrenia-related abnormalities, anorexia, and cognitive impairment; however, the animal studies are rather inconclusive and the predominant finding is that vagotomy increases the risk of anxiety-like behavior (Table S1). [9][10][11][12][13][14][15][16][17][18][19][20] However, on the other hand, the Food and Drug Administration (FDA) approved vagus nerve stimulation in 2005 as a treatment for severe therapy-resistant depression. 21 This was partly as a result of an observed mood improvement in patients with epilepsy treated with vagus nerve stimulation and also neuroimaging studies suggesting an indirect effect of vagus nerve stimulation on cortical structures involved in mood regulation.…”

Comments on “Assessment of changes in the liver of pregnant female rats and their fetuses following monosodium glutamate administration” by Gad El-Hak et al., http://doi.org/10.1007/s11356-021–13,557-7

“…Moreover, in the studies conducted under standard feeding conditions, rats with free access to water containing MSG did not show any rise in the blood concentrations of amino acids. Even if MSG is consumed in large amounts under these study conditions, blood levels of amino acids, including glutamate, were shown to be maintained at almost constant levels (Kondoh & Torii 2008 ; Nishigaki et al 2018 ).…”