MSG-treated Rats Research Articles

Depletion of brain α-MSH alters prostaglandin and interleukin fever in rats

Alpha-melanocyte stimulating hormone (α-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E 1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P < 0.05) than those of the controls for the lower dose of PGE 1 at 10–30 min and for IL-1 at 3–6 h after the injections. MSG-treated rats showed significant reduction (P < 0.01) in α-MSH content of the medial basal hypothalamus and lateral septum when compared to saline controls. Body temperature response of non-febrile animals to high ambient temperature was not affected by the MSG treatment. These data support the hypothesis that α-MSH is an endogenous antipyretic in the rat.

Blockade of the Selective Increase in Serum Follicle-Stimulating Hormone Concentration in Immature Female Rats and its Effects on Ovarian Follicular Development1

We investigated whether administration of monosodium L-glutamate (MSG) to neonatal female rats would block the selective increase in serum follicle-stimulating hormone (FSH) concentration in immature rats in an attempt to provide a model in which to study the importance of the selective FSH rise on ovarian follicular development. In two separate experiments, s.c. injections of MSG (4 mg/g BW) on Days 1, 3, 5, 7 and 9 after birth blocked the selective increase in serum FSH concentration observed on Days 7 and 15 without blocking basal FSH secretion. Serum luteinizing hormone (LH) levels were unaffected in the first experiment and changed little in the second. MSG-treated rats had smaller ovaries on Days 15 and 23. The ovaries of MSG-treated rats on Day 15 showed decreased follicular growth as evidenced by a decrease in the number and percentage of follicles with diameters greater than 50 microns, in the number of follicles with greater than 1 layer of granulosa cells, and in the number of follicles beyond the primary stage of follicular development. These differences between MSG-treated rats and controls all but disappeared by Day 23. The results demonstrate that neonatal administration of MSG blocks the selective increase in serum FSH concentration in immature female rats and suggest that this selective increase in serum FSH levels plays a role in the normal acceleration of ovarian follicular development but is not needed for the development of preovulatory follicles by the sixth week after birth.

Influence of Pinealectomy on Sexual Behavior of Normal and Monosodium L-Glutamate-Treated Rats

Subcutaneous injections of monosodium L-glutamate (MSG) were administered, as a neurotoxin, at a dose of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. Pinealectomy was performed at 6 weeks of age, and animals were allowed to mature. The intact MSG-treated rats showed a decrease of lordosis quotient in females and a reduction of ejaculation frequency and an increase in mount frequency in males. Pinealectomy caused no significant improvement on sexual behavior of the saline-treated normal rats, but it caused a marked improvement of the sexual receptivity in MSG-treated female rats and reinstated ejaculation in MSG-treated males. The circulatory sex steroid levels, estrogen in females and androgen in males, were not significantly different between the intact and pinealectomized MSG-treated groups in the respective sexes, whereas the progesterone level in females was significantly elevated in the pinealectomized MSG-treated group compared with the intact MSG-treated group. These findings suggest that the pineal gland plays an inhibitory role on the sexual behavior of MSG-treated rats and the improvement of sexual behavior following pinealectomy may be dependent on certain mechanisms other than the actions of circulatory androgens or estrogens.

Depletion of Serum Growth Hormone in Adult Female Rats by Neonatal Monosodium Glutamate Treatment without Loss of Female-Specific Hepatic Enzymes P450 2d (IIC12) and Steroid 5α-Reductase*

The sexually dimorphic profiles of pituitary GH secretion play a key role in regulating the expression of several sex-dependent and developmentally controlled P-450 enzymes in rat liver. Current models for P-450 regulation by GH, however, are primarily based on hypophysectomy and GH replacement experiments. The present study examines the effects on hepatic P-450 expression of neonatal injections of monosodium glutamate (MSG), which allows for the nonsurgical suppression of adult GH levels. Furthermore, the levels of other pituitary-dependent hormones, such as testosterone and estradiol, are largely unchanged in the MSG-treated rats. Although hypophysectomy and GH replacement experiments have previously demonstrated that expression of the female-specific hepatic enzymes P-450 2d (gene product IIC12) and steroid 5 alpha-reductase is strikingly dependent on continuous GH exposure, neither enzyme was decreased in adult female rat liver after the elimination of plasma GH (less than 2 ng/ml) by neonatal MSG treatment. Moreover, although the loss of circulating GH appears to be largely responsible for the more than 10- to 20-fold elevation of the male-specific hepatic P-450 forms 2a (gene product IIIA2) and RLM2 (gene product IIA2) in hypophysectomized female rats, no such elevation of the male-specific P-450s was observed in the GH-deficient MSG-treated female rats. In contrast, the female-predominant forms P-450j (gene product IIE1) and 3 (gene product IIA1) were both elevated in adult rat liver after neonatal MSG treatment, in agreement with earlier hypophysectomy studies and demonstrating the suppressive effects that GH can exert on expression of these P-450 forms. Thus, although MSG and hypophysectomy both produce GH depletion, the responsiveness of the hepatic P-450s to these endocrine manipulations differs, allowing for an expanded understanding of the role of GH in P-450 expression.

Depletion of Hypothalamic Growth Hormone-Releasing Hormone by Neonatal Monosodium Glutamate Treatment Reveals an Inhibitory Effect of Betamethasone on Growth Hormone Secretion in Adult Rats

Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH (-74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Signalling Elements in the Ultradian Rhythm of Circulating Growth Hormone Regulating Expression of Sex-Dependent Forms of Hepatic Cytochrome P450*

Neonatal male rats were treated with monosodium glutamate (MSG) at either 2 or 4 mg/g BW on alternate days during the first 10 days of life. As adults, the 4 mg MSG-treated rats displayed the obesity, growth retardation, and reduced pituitary weights that typify this syndrome. These animals had no detectable plasma GH as determined from serial blood samples taken every 20 min for 8 consecutive h. Associated with this loss of circulating GH was an induction of the female-specific hepatic cytochrome P450 2d (gene IIC12) and the disappearance of the male-specific form of cytochrome P450 2c (gene IIC11). The catalytic activities of cytochrome P450 2c (i.e. androgen 16 alpha- and 2 alpha-hydroxylase), sex-dependent hexobarbital hydroxylase and total cytochrome P450 were similarly feminized. Rats exposed to the 2-mg dose of MSG were also obese, but their growth rates and pituitary sizes were not as severely affected as in the 4 mg MSG-treated rats. Circulating GH in these lower dosed males was secreted in a pulsatile pattern similar to that in normal males, except that the pulse amplitude was reduced as much as 90%. In spite of this profound decline in GH peak heights in the 2 mg MSG-treated males, liver metabolism was characteristically masculine. That is, female-specific cytochrome P450 2d remained undetectable, while the male forms of cytochrome P450 2c, 2a (gene IIIA2), and RLM2 (gene IIA2), their respective catalytic steroid hydroxylase activities, and associated sex-dependent drug-metabolizing enzymes were expressed at the level of or greater than that in normal males. Thus, while an ultradian pulse of circulating GH is necessary for the characteristically masculine profile of sex-specific forms of hepatic cytochrome P450, neither the amplitude of the secretory peaks nor their total GH content is critical, and these can be greatly reduced from the normal male levels.

Age- and dose-dependent effects of neonatal monosodium glutamate (MSG) administration to female rats

The age- and dose-dependent effects of neonatal MSG were evaluated in pre- and postpubertal female rats. The neurotoxic action of MSG was assessed by examining monoamine content in microdissected regions of the mediobasal hypothalamus. MSG was administered at a dose of 4 mg/g on postnatal days 2 and 4 (MSG-Lo) or on postnatal days 2, 4, 6 and 8 (MSG-Hi). MSG-Hi treatment significantly reduced dopamine (DA) content in the arcuate nucleus (ANH) and lateral median eminence (LME) on postnatal day 21 when compared to NaCl-injected controls. DA content relative to controls was not altered in the ANH or LME postnatal or postnatal day 60 in MSG-Hi, however, norepinephrine (NE) was significantly ( p<0.05) decreased on both postnatal day 21 and 60 in the LME. MSG-Lo treatment significantly ( p<0.05) reduced ANH NE content on postnatal day 60 compared to controls. Both MSG-Hi and MSG-Lo treatment increased 5-hydroxyindoleacetic acid content in the preoptic area (POA) on postnatal day 60 relative to the controls. Developmental changes independent of MSG treatment were noted in the hypothalamus. DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in the POA were 2-3-fold higher on postnatal day 21 compared to postnatal day 60. In contrast, DA content increased with age in the ANH, LME and medial ME. NE content in the ANH increased as a function of age in controls, but not in MSG-treated rats. The effects of MSG treatment on the postnatal development and maturation of neurons in the mediobasal hypothalamus were discussed in relation to the direct neurotoxicity of MSG.

Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

A pharmacological analysis of food intake regulation in rats treated neonatally with monosodium L-glutamate (MSG)

Studies were conducted to examine deficits in food intake regulation in MSG-treated rats that result from known or suspected damage to neurotransmitter systems involved in feeding. Male rats were injected with either MSG (4 mg/g) or sodium chloride on postnatal days 2 and 4 (MSG-Lo) or postnatal days 2, 4, 6 and 8 (MSG-Hi). As adults, MSG-treated and control rats (n = 12/group) were examined for deficits in pharmacologically elicited feeding and other measures of food intake regulation. A second group of MSG-treated (n = 9/group) and control rats (n = 12) were used to measure basal blood pressure and nociceptive reactivity in adulthood. Organ weights, body weight and neuropeptide Y (NPY) content in brain regions were determined at the end of the study. MSG-Hi rats consumed significantly less food than controls during the dark part of the light cycle. Both MSG-Hi and MSG-Lo groups ate significantly less food than controls after a 48-hour fast. MSG-Hi and MSG-Lo rats consumed significantly less food than controls in response to 1.0 mg/kg morphine. MSG-Hi rats consumed significantly less food than controls during the dark phase and significantly more food than controls during the light phase in response to naloxone (1.0 mg/kg). MSG-Lo ate significantly more than controls in response to 0.1 mg/kg guanfacine. MSG-Hi and MSG-Lo showed a significant attenuation in diazepam-stimulated feeding when compared to controls. Blood pressure was significantly lower in both MSG-Hi and MSG-Lo rats compared to controls. Tail flick latencies were not altered by MSG-treatment. Both doses of MSG produced significant reductions in anterior pituitary, testicular, adrenal and kidney weights relative to the controls. NPY content was significantly reduced in the hypothalamus of MSG-treated (Hi and Lo) rats, but not in other brain regions. The relationship between MSG-induced neurotoxicity and the behavioral and neurochemical deficits of MSG-treated rats was discussed.

Effects of Neonatal Administration of Monosodium Glutamate on Four Neuropeptide Concentrations in the Rat Brain

The present study was designed to measure concentrations of four neuropeptides in different brain regions in monosodium glutamate(MSG)-treated rats and to assess molecular forms of each peptide with gel and high performance liquid chromatography (HPLC). MSG(4mg/kg body weight) or 10% NaCl was injected subcutaneously on postnatal days 1, 3, 5, 7 and 9 to male littermates which were subsequently used on postnatal day 100. Rats were sacrificed by decapitation, and the brains were dissected into ten discrete regions. The brain extracts were subjected to measurement of four neuropeptides; somatostatin (SRIF), neuropeptide Y (NPY), atrial natriuretic polypeptide(ANP), and a novel pituitary polypeptide 7B2 by specific radioimmunoassays. Significant increase (p less than 0.01) in midbrain SRIF content was observed in MSG-treated rats, though there was no significant change in hypothalamic SRIF content. Significant reduction (p less than 0.05) in hypothalamic NPY content was also found in MSG-treated rats. Hypothalamic ANP content was similar in both MSG-treated and control rats. A significant increase of 7B2 content was found in substantia nigra/ventral tegmentum and hypothalamus (p less than 0.05 or p less than 0.01, respectively) in MSG-treated rats. These four immunoreactivities were further characterized by gel permeation or high pressure liquid chromatography (HPLC). Chromatographic analysis of SRIF immunoreactivity revealed that there were two distinctive peaks and smaller molecular weight component corresponding to SRIF. Fractionation of NPY or 7B2 immunoreactivity by gel permeation showed a single major peak which was identical to the synthetic NPY or 7B2 immunoreactivity from porcine pituitary extract. HPLC analysis for ANP immunoreactivity also showed that the major immunoreactive component corresponded to synthetic rat ANP. MSG treatment could not produce any major alterations in proportions of molecular forms studied. These results suggest that MSG treatment in neonates might produce the alterations in SRIF, NPY and 7B2 content in the discrete brain regions including the hypothalamus.

Effects of neonatal monosodium-L-glutamate treatment on rat alveolar macrophages

Treatment of neonatal rats with repeated doses of monosodium-L-glutamate resulted in changes of morphology and function of alveolar macrophages recovered from adult female rats. Numerous cellular lipid vacuoles and lamellar structures were observed in these alveolar macrophages under transmission electron microscopy. There was approximately 50% increase of cellular total lipid content measured by Oil-Red-O staining and colorimetric method. The yeast phagocytosis and intracellular killing ability, as well as the inhibitory effect on the growth of tumor cells were reduced in alveolar macrophages from neonatal MSG-treated rats.

Effects of hypophysectomy on the sleep of neonatally Monosodium Glutamate-treated rats

Monosodium Glutamate (MSG), known to induce neuronal cell degeneration of the arcuate nucleus of the hypothalamus, was subcutaneously injected (4 mg/g body wt.) at postnatal days 1 to 5 or 1 to 10 in female rats. Hypophysectomy was performed at 45–60 days of age. Sleep parameters were continuously recorded for at least 7 days. Results indicated that hypophysectomized (HYPX) NaCl-treated rats showed an increase of Slow Wave Sleep (SWS) (+29.6%) and a decrease of Paradoxical Sleep (PS) (−36.7%) durations. In MSG-treated rats, hypophysectomy did not alter SWS durations but it increased PS durations as MSG dosing increased. It was concluded that arcuate nucleus neurons seemed to be not critically involved in sleep production mechanisms.

Alteration of hepatic drug metabolizing activities and contents of cytochrome p-450 isozymes by neonatal monosodium glutamate treatment

By the treatment of newborn male rats with monosodium glutamate (MSG), microsomal benzo[ a]pyrene hydroxylation, propoxycoumarin O-depropylation, and testosterone (T) 6β- and 2βhydroxylations in the adult rats were decreased significantly, while microsomal aniline and T 7αhydroxylations were increased. However, the treatment of newborn female rats did not significantly alter any of the drug-metabolizing activities examined, except that T 6β-hydroxylation and androstenedione formation were slightly increased. The hepatic contents of male-specific cyt. P-450, P-450-male and P-450 6β, which show high catalytic activities on respective T 16α/2α−, and T 6β/2β-hydroxylations, decreased in MSG-treated male rats. The level of the female specific enzyme, P-450-female, slightly decreased in the MSG-treated female rats, whereas higher phénobarbital (PB)-induction of PB-inducible isozymes, P-450b and P-450e, was observed in MSG-treated than in control female rats. These results are consistent with the idea that disruption of a pulsatile secretion of growth hormone, which is induced by the neonatal MSG treatment, leads to changes in drug metabolizing activities through the alteration of the levels of sex-specific cyt. P-450s, but also indicate that MSG-treated rats are not an animal model equivalent to hypophysectomized rats.

Hypophysectomy in monosodium glutamate-pretreated rats suppresses paradoxical sleep rebound

Control untreated and pretreated female rats at birth with 10 injections of monosodium glutamate (MSG, 4 mg/g b. wt.) were hypophysectomized (HYPX) at 45–60 days of age and their sleep-waking cycle continuously registred. In control rats, hypophysectomy was followed by a 35.7% decrease in paradoxical sleep (PS) duration while it has no effect on the sleep of MSG-treated rats. After 24 h of PS deprivation, there was a normal immediate rebound of PS in the control HYPX and MSG rats while there was no significant rebound in the HYPX-MSG-treated rats. It is concluded that neuropeptides from arcuate nucleus and hypophysis are involved in a PS rebound mechanism.

Neonatal monosodium- l-glutamate treatment reduced lipolytic response of rat epididymal adipose tissue

1. 1. The effect of neonatal monosodium- l-glutamate (MSG) treatment on lipolysis in rat epididymal adipose tissue was studied. A reduction in the basal lipolysis was observed in the MSG-treated rats. 2. 2. This was accompanied by a decreased lipolytic response to isoprenaline, adrenocorticotropic hormone, forskolin, isobutylmethylxanthine and dibutyryl-cAMP. 3. 3. The addition of adenosine deaminase, which inactivates endogenous adenosine in the medium, did not normalize the basal and the hormone stimulated lipolytic responses. 4. 4. The maximal lipolysis stimulated by adenosine deaminase or 8-( p-sulfophenyl)-theophylline (8-SPT), an adenosine antagonist, was significantly lower in the MSG-treated rats. 5. 5. Moreover, there was no change in the sensitivity of adenosine receptors to its antagonist as reflected by the similar potency of 8-SPT in eliciting the lipolytic response in both the control and MSG-treated rats. 6. 6. In conclusion, neonatal MSG treatment in rats induced a general reduction of lipolytic response in the epididymal adipocytes which cannot be explained by an enhancement of the adenosine inhibitory system.

Neonatal treatment with monosodium glutamate increases plasma corticosterone in the rat.

Monosodium glutamate (MSG) has been shown to alter several neuroendocrine functions in neonatally treated rats. To evaluate for possible alterations in the hypothalamic-pituitary-adrenal axis, we injected rats during the neonatal period with MSG or saline (controls). An increase in basal plasma corticosterone levels associated with a blunted circadian variation was observed. Ether exposure produced a significant elevation in plasma corticosterone concentration in both groups of animals. However, while the increase in controls was 181.3% for male and 193.9% for female rats, in the MSG-treated rats it was only 60.7 and 31.6%, respectively. The intraperitoneal administration of high dexamethasone doses blocked corticosterone secretion in both groups. However, whereas the lowest dose (0.10 microgram/kg) suppressed corticosterone secretion in control animals, it was ineffective in MSG-treated rats. The morphological study of adrenals revealed signs of a hyperfunctional state in MSG-treated rats. These data suggest that the central lesions produced by MSG treatment disrupt the regulation of the hypothalamic-pituitary-adrenal axis.

Regulation of the Central Nervous System-Pituitary-Adrenal Axis in Rats after Neonatal Treatment with Monosodium Glutamate

We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6-7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (3H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (approximately equal to 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.

Prevention of reflex natriuresis after acute unilateral nephrectomy by neonatal administration of MSG.

Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. We measured plasma immunoreactive NTF-like material (IR-NTF) before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increased from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN (P less than 0.02) as sodium excretion (UNaV) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration (58.8 +/- 21.3 vs. 68.3 +/- 18.5 fmol/ml (P = NS), nor did UNaV increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natriuresis after AUN, and therefore lend further support to the concept of a causal relationship between these two consequences of AUN.

Monosodium glutamate投与による実験的肥満ラットのリポ蛋白代謝異常:トリグリセライド分泌速度およびpostheparin lipolyticactivity

We have reported that the monosodium glutamate (MSG)-induced obese rats develop hypertriglyceridemia due to increment of VLDL. In order to clarify the mechanisms of hypertriglyceridemia in MSG-treated rats, triglyceride secretion rates (TGSR) and postheparin lipolytic activities (PHLA) were studied. MSG (4mg/g body weight/day) was injected subcutaneously to the neonatal Wistar rats for 5 days. Experiments were performed using the rats fasted for 14 hours, 24 weeks after MSG injection. TGSR was calculated from the differences in plasma triglyceride concentrations before and 90 minutes after intravenous injection of Triton WR 1339 (135 mg/rat). Postheparin lipolytic activities were measured in plasma obtained from the rats, 3 minutes after injection of heparin, 50 U/250 g body weight. Higher Lee's indices were observed in the MSG-treated rats. Plasma concentrations of triglycerides were 361.5±50.8mg/dl (control 100.4±12.8mg/dl) and 883.2±180.6mg/dl (control 72.9±12.0mg/dl) in male and female MSG rats, respectively. TGSR was significantly increased in the MSG-treated rats (male: MSG 495.1±71.2, control 233.8±12.8mg/dl/hr, p<0.005; female rats: MSG 672.5±22.5, control 399.7±29.8mg/dl/hr, p<0.001). TGSR showed the positive correlation to plasma concentrations of triglycerides (male rats: r=0.75, p<0.005; female rats: r=0.77, p<0.005). Significantly increased levels of plasma IRI (male rats: 15.13±2.16 vs. 6.08±0.35, μU/ml, p<0.005; female rats: 9.53±1.20 vs. 4.42±0.32μU/ml, p<0.005) correlated positively to TGSR. There were no significant differences in total PHLA. However, increased activities of lipoprotein lipase (5.22±0.23, vs. 3.75±0.36μmol/ml/hr) and decreased activities of hepatic triglyceride lipase (10.16±0.26 vs. 11.12±0.22μmol/ml/hr) were observed in the male MSG-treated rats. The data presented indicated that increased TGSR induced by hyperinsulinemia plays an important role in hypertriglyceridemia observed in the MSG-induced obese rats.

Neurotoxin effects on oxytocin, vasopressin and somatostatin in discrete rat brain areas

Monosodium-L-Glutamate (MSG) produces lesions to monoaminergic and peptidergic neurons in several brain areas. The present study examined the effect of neonatal MSG treatment on oxytocin (OXY), arginine-vasopressin (AVP) and somatostatin (SRIF) concentrations in several discrete brain areas of adult rats. OXY increased in the suprachiasmatic and arcuate nuclei and median eminence (ME) and decreased in the paraventricular nucleus of MSG-treated rats. MSG treatment caused AVP to increase in the arcuate nucleus and ME and decrease in the supraoptic nucleus. SRIF decreased following neonatal MSG treatment in both the ME and neurointermediate pituitary lobe. The results demonstrate that the effects of neonatal MSG treatment on neuropeptide content are not just limited to the arcuate nucleus. Furthermore, taken together with previous results, the data suggest that these changes may be indicative of functional deficits in the neuronal activity of some of these peptidergic neurons which, in turn, may be responsible for the abnormal secretion of several pituitary hormones observed in MSG-treated animals.