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ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 1  |  Page : 3-8

Effect of monosodium glutamate (MSG) on behavior, body and brain weights of exposed rats


Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Cross River State, Nigeria

Date of Submission30-Sep-2019
Date of Decision02-Jan-2020
Date of Acceptance13-Feb-2020
Date of Web Publication21-Apr-2020

Correspondence Address:
Uche Stephen Akataobi
Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, P.M.B. 1115, Calabar, Cross River State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ed.ed_31_19

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  Abstract 


Purpose: Consumption of monosodium glutamate (MSG) in food, drink, and other consumables has been linked to different observable changes believed to be as a result of MSG's effects on the brain. Furthermore, it is believed that blood–brain barrier plays a role on how these effects are felt in different stages of life. The present study is an attempt to understand the differential effect of MSG by studying body and brain weights as well as physiological changes in the behavior of rats exposed at different stages of life (either as neonate or as adult).
Materials and Methods: Pups were administered 4 mg/g MSG on postnatal days 2, 4, 6, 8, and 10, allowed to mature for 26 weeks, and afterward divided into three groups (n = 6) and administered saline, 5 mg/g, and 10 mg/g MSG for 6 weeks. Two other groups, not exposed to MSG at neonatal age (adult), were similarly administered 5 mg/g and 10 mg/g MSG for 6 weeks. During this period, weight gain and behavioral observation was made, and at the end of the 6 weeks, brain weight was measured.
Results: A dose-dependent effect of MSG was recorded in both neonatal- and adult-administered rats in all the parameters studied.
Conclusion: MSG affects both neonate and adult rats similarly, thus adult exposure may be used in studies involving MSG and other neurotoxic chemicals.

Keywords: Behavior, brain weight, monosodium glutamate, neurotoxicity, weight gain


How to cite this article:
Akataobi US. Effect of monosodium glutamate (MSG) on behavior, body and brain weights of exposed rats. Environ Dis 2020;5:3-8

How to cite this URL:
Akataobi US. Effect of monosodium glutamate (MSG) on behavior, body and brain weights of exposed rats. Environ Dis [serial online] 2020 [cited 2021 Nov 27];5:3-8. Available from: http://www.environmentmed.org/text.asp?2020/5/1/3/283007




  Introduction Top


Consumption of toxic substances in form of food additives has been reported to present in food, has been reported to have serious effects on the brain's functional capability in exposed individuals, mostly those exposed at infant stage due to the effect of these chemical substances or food additives including monosodium glutamate (MSG) on the functioning of the neurotransmitters.[1] The major component of MSG is glutamate, which exists as one of the most abundant amino acids present in the central nervous system (CNS).[2]

Human brain studies have shown that glutamate serves as a primary excitatory amino acid neurotransmitter with a direct link to the activation of excitatory amino acid receptor that stimulates enzymatic reaction steps that may lead to cell death.[3]

Furthermore, there have been reports about the correlation between high dose of MSG exposure to experimental animals and severe neurotoxicologic effects,[4] retinal degeneration in young mice,[2],[5] significant damages in the hypothalamic neurons with arcuate nucleus, and impaired memory retention in matured mice.[1] It has also been proven that subcutaneous administration of MSG at a high concentration in male neonates induces excitotoxicity, which promotes cell death in the prefrontal cerebral cortex.[6]

According to Russell,[3] there is a scientific evidence that these food additives or chemical substances (called excitotoxin) have the potential to damage critical parts of the brain known to control hormonal activities, leading to observable endocrine defects later in life. This evidence strongly suggests that artificial sweeteners such as MSG present or added to diets, soft drinks, and most easily consumed foods may cause brain tumors and damages in most parts of the brain that control other parts of the body, resulting in avoidable neurodegenerative disease conditions both in young- and adult-exposed humans.[7]

In early stages of life, the effects of these substances according to studies are more observable, which is believed to be due to the inability of the developing blood–brain barrier to completely prevent the entry of most of these harmful substances into the brain,[8] which over time become accumulated in the brain causing series of excitation of the neurons and lots of disease conditions.[9] Exposure to sufficient concentrations of these neurotoxins (MSG) has been shown to be responsible for recorded brain lesions found in children, which becomes irreversible even after growth,[3] unlike a fully developed blood–brain barrier which has been shown to have full control over the type and concentration of chemical substances or neurotoxins that gain access into the brain.[7]

It has also been reported that fully developed brain contain certain regions which may not be completely protected by the blood-brain barrier, which gives unrestricted access to neurotoxins like MSG into the brain causing its accumulation, and results in conditions like Parkinson's and Huntington's disease, possibly Stroke, Brain Tumor and Seizure.[10]

These parts of the brain without blood–brain barrier protection have been reported to include “hypothalamus, circumventricular organs, pineal gland and small nucleus of the brain stem.” These regions of the brain play important roles, for instance, the brain stem (consisting of two hemispheres called cerebellum) generates impulses such as breathing heart rate balance and motor nerve of the face, neck, and cranial nerve.[8] It is also responsible for maintaining alertness while the upper part of the cerebellum promotes the causation of Parkinson's disease.[7]

The hypothalamus controls the release of hormones of the pituitary gland and regulates metabolism, puberty, and growth; it is also important in the regulation of sleep and waking cycle, autonomic system, emotion, biological clocks, fullness, and hunger.[10] The effect of neurotoxins such as MSG on the hypothalamus has been employed in studies involving neonatal obesity induction using MSG; this is as a result of the existing studies suggesting that children are more sensitive to excitoxins in food than adults.[3] Large amount of MSG exposure leads to excess electrical activity and even seizure in newborns and toddlers.[2] The effects of neurotoxin damage during development may include mild dyslexia to severe outbursts of uncontrollable anger, autism, schizophrenia, and cerebral palsy and leads to a serious concern that children exposed at this early stage in life may grow up to be shorter in stature and obese.[3],[11]

Furthermore, in young exposed animals, studies have shown hyperactive behavior with inability to focus, lowered intelligence, as well as defectives in endocrine system in adults.[2] There are also reports that neonatal animals exposed to MSG become obese in weeks, while adult animals similarly exposed do not; this idea has been employed in different studies involving neonatal animals and obesity induction.[11]

Excitotoxins are much more toxic to the brain in their liquid forms than in dry forms due to their ability to be carried in blood, pass the blood–brain barrier, and get absorbed faster.[10] The blood–brain barrier serves as a protective mechanism of the CNS against chemicals reaching the brain from the blood.[3]

In humans, it is also believed that exposure to excitotoxins affects children more, because at this stage of life, the blood–brain barrier is still developing and these toxic substances are easily carried via the blood into the CNS.[12]

According to Russell,[3] the negative effects of excitotoxin are not only limited to small children, but also felt in adults; according to this report, there are a wide range of evidence which suggests that excitotoxins such as MSG play major roles in a good number of degenerative brain diseases in adults mostly in the elderly, because of a slow destruction and damage of brain cells sensitive to a specific excitotoxin common to both age groups, for example, exposure to higher concentration of glutamate only destroys neurons that use glutamate as a transmitter, while neurons of other transmitters are speared.[3],[13] Within this background, this study aimed at comparing the effect of MSG on both neonate and adult rats by studying their behavior and rate of body weight gain and brain weight.


  Materials and Methods Top


Experimental animals

Male and female adult Wistar rats were obtained from the Animal House of the College of Medical Sciences, University of Calabar, Nigeria. The animals were grouped into five, at the ratio of 2:3, with two males and three females in each group, and allowed to mate, after which the pregnant females were further separated into different cages where they littered and raised their offspring (neonate).

Experimental design

Neonatal rats were used as experimental animals in the study according to the method of Rotimi et al.,[11] who administered 4 mg/g of MSG intraperitoneally on postnatal days 2, 4, 6, 8, and 10. After grouping with little adjustment, the rats were grouped after weaning. Experimental animals were distributed into seven groups with six animals in each group. With the exception of the control, animals were given different concentrations of MSG as neonates, adults, or neonates and adults orally reconstituted in water, twice a day (12 h apart).

The control group was administered normal saline, in the same manner. Within the 6 weeks of administration, all the groups were carefully monitored, and changes in their behavior, physical appearance, and weight were monitored at the end of every 2 weeks, and all the animals had free access to feed (rat chow) and water.

At the end of the 6 weeks of study, the rats were fasted overnight, anesthetized in a laboratory glass desiccator using chloroform, and sacrificed; they were decapitated and their skull was cracked and the whole brain was removed and weighed.

Monosodium glutamate treatment

Postnatal exposure

Following the day of delivery, the pups were divided into two groups: Group 1 animals received a single dose of 4 mg/g of MSG (reconstituted in normal saline) via intra-peritoneal route, daily, on postnatal days 2, 4, 6, 8, and 10, whereas Group 2 animals were similarly treated with normal saline, to serve as control animals as described by Rotimi et al.,[11] with little modifications. The rats were weaned on the 21st day and raised normally thereafter and studied at the age of 32 weeks.

Adult exposure

Mature Wistar rats of the same age and size as the group in the section A above, obtained from the same source, were divided into different cages. They were raised and studied along with those in section A [Table 1].
Table 1: Experimental design and grouping of animal

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  Results Top


The data obtained in this study were analyzed using one-way ANOVA at P < 0.05 level of significance, while the physiological results presented in this study are records of physical observations made during the time of the study by watching the animal behavior and physical changes that occurred in their groups.

Effect of monosodium glutamate treatment on brain weight (100 g)

[Figure 1] depicts the mean of result obtained on brain weight following MSG exposure, which indicated a statistically significant (P < 0.05) dose-dependent reduction in brain weight of both neonate and adult MGS groups versus control (0.00000319 100 g) group. The result further showed that at (P < 0.05) the brain weight of the groups treated MSG twice that is 4 mg/g neonate plus 5 mg/g adult (0.00000264 100 g) and 4 mg/g neonate plus 10 mg/g adult (0.00000219 100 g) as well as in adulthood only groups decrease significantly vs neonate only MSG group (0.00000265 100 g).
Figure 1: Brain weight. Values are expressed as mean ± standard error of the mean, n = 6, a = P < 0.05 versus d, f = P < 0.05 versus a

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The effect of MSG recorded in this study occurred in a similar manner in all the MSG groups, and the dose-dependent effects were also similar in both the groups administered MSG either as neonate plus adult and adult only groups.

Effect of monosodium glutamate treatment on body weight

[Figure 2]; Shown the mean of results obtained on body weight. The result [Table 2] indicated a significant (P < 0.05) increase in body weight in the MSG administered groups versus control (17.07 g); with exception of the 4 mg/g body weight MSG neonate only (9.57 g) group, that indicated a significant (P < 0.05) reduction in body weight versus control.
Figure 2: Body weight. Values are expressed as mean ± standard error of the mean, n = 6, a = P < 0.05 versus f, b = P < 0.05 versus a, c = P < 0.05 versus d, e = P < 0.05 versus f

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Table 2: Mean±standard error of mean of brain and body weight

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Furthermore the result indicated a dose dependent significant (P < 0.05) increase in all the MSG groups, higher in adult only administered groups 5 mg/g body weight MSG adult only (35.56 g) and 10 mg/g body weight MSG adult only (60.83 g) followed by the groups administered both as neonate plus adult 4 mg/g body weight MSG neonate plus 5 mg/g body weight adult (10.59 g) and 4 mg/g body weight MSG neonate plus 10 mg/g body weight MSG adult (26.35 g) in a dose dependent manner significantly higher vs the neonate only treated group 4 mg/g body weight MSG neonate.

From these results, MSG administration caused a significant (P < 0.05) reduction in brain weight obtained by dividing the brain weight by the final body weight and expressing it in 100 g; the results also indicated that the higher the dose, the more the reduction in the weight of the brain (comparing 4 mg/g body weight MSG neonate plus 5 mg/g body weight MSG adult with 4 mg/g body weight MSG neonate plus 10 mg/g body weight MSG adult) as well as (5 mg/g body weight MSG adult only and 10 mg/g body weight MSG adult only.

It has also been indicated in the result that MSG administration caused reduction in body weight following neonatal administration (comparing control with 4 mg/g body weight MSG neonate only), but there was a statistically significantly (P < 0.05) increase following administration at adulthood in a dose-dependent manner.

Physiological and behavioral observation

Neurological abnormalities

This was seen to be more common to the groups administered with MSG at 4 mg/g neonate plus 10 mg/g adult and 10 mg/g adult per body weight. These groups showed the symptom of not being stable (like one part of their body is paralyzed such as in stroke) and in all times kept turning around toward the bent side and were unable to move toward the other side.

Body movement, weakness, and sudden death

In all the administered groups, as the days of administration increased, the rats were seen to show weakness and reduced movement when compared to the control groups which never exhibited this symptom, with more rats from the groups that received 10 mg/g adult, per body weight, showing more of this effect.

Rats in groups that were administered 4 mg/g body weight MSG neonate plus 10 mg/g body weight MSG adult, and 4 gm/g body weight MSG neonate plus 5 mg/g body weight MSG adult exhibited sudden deaths as the administration days increased which was observed to occurred within 20 min following administration in adult hood, but were not seen in groups administered MSG in the same dose/concentration as adults only or in the control groups, suggesting that neonatal exposure contributed to this effect.

Loss of some eye cells

In groups administered 4 mg/g body weight MSG neonate plus 10 mg/g body weight MSG adult and 10 mg/g body weight MSG adult only were mostly affected by this symptom, after the 1st week of administration, some members of these groups started losing their eye sight, their right eye cells started changing color from red to brown [Figure 3], and as the days of administration increased, the eyes turned black completely followed by bleeding and its loss (the eye cavity appeared empty) and in a day or two following this, the left eye was affected and lost too, followed by the death of the rat.
Figure 3: Loss of eye cells

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Development of boils and running nose

In groups administered 5 mg/g body weight MSG adult only and 10 mg/g body weight adult only a common symptoms was observed developed under their neck and in group administered 4 mg/g body weight MSG neonate only group by their arm [Figure 4], there was an abnormal growth which appeared like boils and increased in size as the administration days increased, this was followed by running nose (bleeding noses) in these affected animals, proceeded by the loss of weight and death.
Figure 4: Development of boil-like growth

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  Conclusion/discussion Top


Following the 6-week MSG administration, a dose-dependent effect on the eye of groups administered with higher dose either as neonate plus adult or as adult only was observed; this observation showed that at higher doses of exposure, MSG has a significant effect on the eyes [Figure 3] of the animals; this result is in line with the report of Collison et al.,[14] which reported that a single dose of 1 μmol MSG administered intravenously to Sprague–Dawley rat led to increased glutamate concentration in the CNS, which stimulates damages in various structures of the eye such as the retina.

The result suggested that the stern degenerative changes occurred in two stages: first massive intracellular swelling and necrosis and second complete disappearance of the inner retinal neurons accompanied by thinning of the inner retina. Also, Konrad et al.[15] reported that MSG administered at higher dose during early postnatal days led to severe loss of ganglion and interneurons in the retina, in young mice exposed with MSG. Lucos and Newhouse reported retinal degeneration and loss of eye cells. These effects reported in these studies agree with the observation made in this present study on the effect of MSG exposure on the eye cell of rats [Figure 3].

This report suggests that MSG's effect on the eye cells is as a result of overexcitation of glutamate neurons directly or indirectly linked to retina, and as the days of administration increased, the eyes turned black completely followed by bleeding and its loss (the eye cavity appeared empty) and in a day or two following this, the left eye (other eye) became affected and lost too, followed by the death of the rat.[14]

Exposure to higher concentration of MSG results in an uncontrolled elevation in the level of excitotoxic neurotransmitter glutamate that affects most functions of the CNS including motor skill,[3] reported that as a neurotransmitter glutamate participate, in a wide range of brain activities including orientation and motor skills. And at higher concentration results in neurological abnormalities mostly felt at adult age.[16] This may be evidenced of the neurological abnormalities observed in this study, especially in movement of the rats exposed to a higher concentration of MSG, suggesting that MSG exposure leads to increases in the level of glutamate in the CNS, resulting in impaired motor skills, movement, orientation, and cognition.[15]

These reports are in line with our observation on the effect of high concentration of MSG exposure to rats, which caused the affected animals to lose control of their movement, favoring a particular side by constantly binding towards that side which were observed in this present study.

Furthermore, results from animal studies involving neonatal administration of MSG have shown a the development of obesity in adult hood, following neonatal exposure to MSG. which have led to concerns about obesity in individuals consuming MSG in diets and other consumables such drinks.[14] In this study, a similar pattern of weight increase was recorded in both neonate and adult exposed groups, which suggests that MSG effect on body weight gain is not only attributed to its effect on developing blood brain barrier of the exposed neonate, but the rats were similarly affected in adult hood in the same manner.[3],[11]

The link between MSG exposure and obesity induction has been found to be as a result of association between neurotransmission signaling process of glutamate with energy balance and interruption in the hypothalamic signaling process of leptin[17] that causes the exposed animal to eat more food while showing less movement or exercise,[16] as was observed in the present study.

The basis of obesity induction was explained by Collison et al.[14] using 19-week-old rats injected with 2 mg/g MSG on postnatal days 2, 4, and 4 mg/g on days 6, 8, and 10 and suggested that the increase in monitored body weight was linked to leptin activity in the visceral adipose tissue.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Igwebuike UM, Ochiogu IS, Ihedinihu BC, Idika I. Effects of oral administration of monosodium glutamate (MSG) on the testicular morphology and caudaepididymal sperm reserves of young and adult male rats. Vet Arch 2011;81:525-34.  Back to cited text no. 1
    
2.
Srivastava A, Eshita P, Khanam S. Behavioural effects of MSG on abino rats. Int J Biopharm 2014;5:46-50.  Back to cited text no. 2
    
3.
Russell LB. Excitotoxins, the Taste that Kill's. Albuquerque NM 87176: Health Press NA Inc.; 1997. p. 63-100.  Back to cited text no. 3
    
4.
Park CH, Choi SH, Piao Y, Kim S, Lee YJ, Kim HS, et al. Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice. Toxicol Lett 2000;115:117-25.  Back to cited text no. 4
    
5.
Lucas DR, Newhouse JP. The toxic effect of sodium L-glutamate on the inner layers of the retina. AMA Arch Ophthalmol 1957;58:193-201.  Back to cited text no. 5
    
6.
González-Burgos I, Pérez-Vega MI, Beas-Zárate C. Neonatal exposure to monosodium glutamate induces cell death and dendritic hypotrophy in rat prefrontocortical pyramidal neurons. Neurosci Lett 2001;297:69-72.  Back to cited text no. 6
    
7.
Okon AK, Jacks TW, Amaza DS, Tarfa MP, Eduitem SO. The effect of monosodium glutamate (MSG) on the gross weight of the heart of albino rats. Scholars J Appl Med Sci 2013;1:44-7.  Back to cited text no. 7
    
8.
Shi Z, Yuan B, Anne WT, Grande ED, Gary AW. Amino acids – Monosodium glutamate intake increase hemoglobin level over 5 years among Chinese adults. Springer Vienna: Springer International Publishing AG; 2012.  Back to cited text no. 8
    
9.
Abu-Taweel GM, Ajarem JS, Ahmad M. Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice. Neurotoxicol Teratol 2014;42:60-7.  Back to cited text no. 9
    
10.
Peterson DR. Blood-brain barrier. In:elS. Neuro Science. John wily & Sons, Ltd: Chchestr. 2012. DOI: 10.1002/9780470015902.a0000023.pub3.  Back to cited text no. 10
    
11.
Rotimi OA, Olayiwola IO, Ademuyiwa O, Balagun EA. Effects of fiber-enriched diet on tissue lipid profile of MSG obese rats. J Food Chem Toxicol 2012;50:4062-7.  Back to cited text no. 11
    
12.
Richard AH. The blood-brain barrier and glutamate. Am J Clin Nutr 2009;3:57-98.  Back to cited text no. 12
    
13.
Richard AH, Juan RV. How glutamate is managed by the blood-brain barrier. J Biol 2016;31:507-98.  Back to cited text no. 13
    
14.
Collison KS, Makhoul NJ, Zaidi MZ, Al-Rabiah R, Inglis A, Andres BL, et al. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Nutr Metab (Lond) 2012;9:58.  Back to cited text no. 14
    
15.
Konrad SP, Farah V, Rodrigues B, Wichi RB, Machado UF, Lopes HF, et al. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents. Clinics (Sao Paulo) 2012;67:1209-14.  Back to cited text no. 15
    
16.
Roman-Ramos R, Almanza-Perez JC, Garcia-Macedo R, Blancas-Flores G, Fortis-Barrera A, Jasso EI, et al. Monosodium glutamate neonatal intoxication associated with obesity in adult stage is characterized by chronic inflammation and increased mRNA expression of peroxisome proliferator-activated receptors in mice. Basic Clin Pharmacol Toxicol 2011;108:406-13.  Back to cited text no. 16
    
17.
He K, Du S, Xun P, Sharma S, Wang H, Zhai F, et al. Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS). Am J Clin Nutr 2011;93:1328-36.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]


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[Pubmed] | [DOI]



 

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