Search

[Display omitted] • Monosodium glutamate aggravates lipopolysaccharide-induced neurobehavioral deficits and oxidative stress. • Monosodium glutamate worsens lipopolysaccharide-induced cholinergic dysfunction and neuroinflammation. • Monosodium glutamate exacerbates lipopolysaccharide-triggered neurodegeneration. Extensive experimental evidence points to neuroinflammation and oxidative stress as major pathogenic events that initiate and drive the neurodegenerative process. Monosodium glutamate (MSG) is a widely used food additive in processed foods known for its umami taste-enhancing properties. However, concerns about its potential adverse effects on the brain have been raised. Thus, the present study investigated the impact of MSG on lipopolysaccharide (LPS)-induced neurotoxicity in rat brains. Wistar rats weighing between 180 g and 200 g were randomly allocated into four groups: control (received distilled water), MSG (received 1.5 g/kg/day), LPS (received 250 µg/kg/day), and LPS + MSG (received LPS, 250 µg/kg, and MSG, 1.5 g/kg). LPS was administered intraperitoneally for 7 days while MSG was administered orally for 14 days. Our results showed that MSG exacerbated LPS-induced impairment in locomotor and exploratory activities in rats. Similarly, MSG exacerbated LPS-induced oxidative stress as evidenced by increased levels of malondialdehyde (MDA) with a concomitant decrease in levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-s-transferase (GST) in the brain tissue. In addition, MSG potentiated LPS-induced neuroinflammation, as indicated by increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) as well as myeloperoxidase (MPO) and nitric oxide (NO) in the brain. Moreover, MSG aggravated LPS-induced cholinergic dysfunction, as demonstrated by increased activity of acetylcholinesterase (AChE) in the brain. Further, we found a large number of degenerative neurons widespread in hippocampal CA1, CA3 regions, cerebellum, and cortex according to H&E staining. Taken together, our findings suggest that MSG aggravates LPS-induced neurobehavioral deficits, oxidative stress, neuroinflammation, cholinergic dysfunction, and neurodegeneration in rat brains. [ABSTRACT FROM AUTHOR]

Epidemiological surveys show that 70–80% of patients with Alzheimer’s disease (AD) have type 2 diabetes mellitus (T2DM) or show an abnormality of blood glucose levels. Therefore, an increasing number of evidence has suggested that diabetic hyperglycemia is tightly linked with the pathogenesis and progression of AD. In the present study, we replicated T2DM animal model via subcutaneous injection of newborn Sprague-Dawley (SD) rats with monosodium glutamate (MSG) during the neonatal period to investigate the effects and underlying mechanisms of hyperglycemia on cognitive ability. We found that neonatal MSG exposure induced hyperglycemia as well as Alzheimer-like learning and memory deficits with decreased dendritic spine density and hippocampal synaptic-related protein expression and increased phosphorylated tau levels in ∼3-month-old SD rats. Our results suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD. [ABSTRACT FROM AUTHOR]

The effects of aging on the umami sensation were compared between the preference and neural responses from the greater superficial petrosal nerve (GSP innervating the soft palate) and the chorda tympani nerve (CT innervating the fungiform papillae) in the Sprague Dawley rat. A two-bottle preference test revealed that younger rats (5-12 weeks) preferred significantly 0.001 M 5'-inosine monophosphate (IMP), 0.01 M mono sodium glutamate (MSG), and binary mixtures of 0.001 M IMP + 0.01 M MSG than deionized water. However, aged rats (21-22 months) showed no significant preference to these umami solutions compared to deionized water. Among the other four basic taste stimuli, there were no significant differences in preference between young and aged rats. Regardless of the age of the rat, neural responses from the GSP and CT produced robust integrated responses to all three umami solutions used in the two-bottle tests. These results indicate that the lack of preference to umami in aged rats is a central nervous system phenomenon and suggests that the loss of preference to umami taste in aged rats is caused by homeostatic changes in the brain incurred by aging. [ABSTRACT FROM AUTHOR]

Abstract: The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity. [Copyright &y& Elsevier]

Abstract: Osteoarthritis (OA) is a chronic pain condition characterized by pain during joint use as well as pain at rest (i.e., ongoing pain). Although injection of monosodium iodoacetate (MIA) into the intra-articular space of the rodent knee is a well established model of OA pain that is characterized by changes in weight bearing and hypersensitivity to tactile and thermal stimuli, it is not known if this procedure elicits ongoing pain. Further, the time-course and possible underlying mechanisms of these components of pain remain poorly understood. In these studies, we demonstrated the presence of ongoing pain in addition to changes in weight bearing and evoked hypersensitivity. Twenty-eight days following MIA injection, spinal clonidine blocked changes in weight bearing and thermal hypersensitivity and produced place preference indicating that MIA induces ongoing and evoked pain. These findings demonstrate the presence of ongoing pain in this model that is present at a late-time point after MIA allowing for mechanistic investigation. [Copyright &y& Elsevier]

Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This effect has been proven in different models of retinal degeneration. We have previously shown that PACAP protects against monosodium-glutamate (MSG)-induced damage in neonatal rats. The beneficial effects of enriched environment, another neuroprotective strategy, have long been known. Environmental enrichment has been shown to decrease different neuronal injuries. It also influences the development of the visual system. We have recently demonstrated that significant neuroprotection can be achieved in MSG-induced retinal degeneration in animals kept in an enriched environment. Combination of neuroprotective strategies often results in increased protection. Therefore, the aim of the present study was to compare the two neuroprotective strategies alone and in combination therapy. We found that both PACAP and environmental enrichment led to a similar degree of retinal protection, but the two treatments together did not lead to increased protection: their effects were not additive. [Copyright &y& Elsevier]

Abstract: The effect of stimulation of the vestibular nuclear complex (VN) on the masseteric monosynaptic reflex (MMR) was studied in anesthetized rats. The MMR was evoked by electrical stimulation of the mesencephalic trigeminal nucleus and was recorded, bilaterally, as the electromyographic responses of the masseter muscles. Conditioning electrical stimulation of the medial vestibular nucleus (MVN) facilitated the MMR bilaterally, as did microinjection of monosodium glutamate into the MVN. In contrast, conditioning electrical stimulation of the inferior vestibular nucleus (IVN) inhibited the MMR bilaterally. Microinjection of monosodium glutamate into the IVN also inhibited the MMR bilaterally. Conditioning electrical stimulation of the lateral and superior vestibular nuclei did not modulate the MMR. These results suggest that the MVN and the IVN are involved in modulation of the MMR and plays an important role in controlling jaw movements. [Copyright &y& Elsevier]

Abstract: The effect of stimulation of the vestibular nuclear complex (VN) on the jaw-opening reflex (JOR) was studied in anesthetized rats. The JOR was evoked by electrical stimulation of the inferior alveolar nerve, and was recorded as the electromyographic responses of the anterior belly of the digastric muscle, bilaterally. Conditioning electrical stimulation of the medial (MVN), lateral (LVN) and superior (SVN) vestibular nuclei facilitated the JOR bilaterally. Microinjection of monosodium glutamate into the SVN, LVN and MVN also facilitated the JOR bilaterally. In contrast, conditioning electrical stimulation of the inferior vestibular nucleus (IVN) inhibited the JOR ipsilaterally. Microinjection of monosodium glutamate into the IVN also inhibited the JOR ipsilaterally. These results suggest that the VN is involved in modulation of the JOR and plays an important role in controlling the jaw movements. [Copyright &y& Elsevier]

Abstract: Monosodium glutamate as well as metabotropic and ionotropic glutamate receptor agonists have been reported to be perceived as umami by humans. In spite of the fact that Tas1R1–Tas1R3 has been shown to mediate most of the glutamate taste sensation in mice other candidate receptors have been put forward for which a clear role in detection is still lacking. This work was aimed at investigating the molecular determinants underlying umami taste detection in humans. First, we show evidence supporting expression of Tas1R1 and Tas1R3 but not mGluRs in the fungiform papillae of several individuals. Next, we report a number of naturally occurring l-glutamate taste receptor variants and their frequency in a population of Caucasian subjects. Detailed analysis of 9 non-synonymous single nucleotide polymorphisms from three l-glutamate taste GPCR candidates uncovers receptor specific clusters such that all substitutions in Tas1R1 are located in the extracellular N-terminal ligand-binding domain while in Tas1R3 they mostly affect residues in the seven transmembrane-spanning core domain responsible for the interaction with antagonists and allosteric modulators. In mGluR1, nsSNPs identified are clustered in the intracellular C-terminal tail, which is thought to play a role in signaling. Taken together, these results suggest that Tas1R1–Tas1R3 receptor variants found in human fungiform papillae might contribute to inter-individual differences of sensitivity to l-glutamate. [Copyright &y& Elsevier]

Abstract: The preference for foods or fluids in rats is partly dependent on its postingestive consequences. Many studies have investigated postingestive effect of high caloric substances, such as carbohydrate or fat. In this study, we examined postingestive effect of l-glutamate at the preferable concentration using conditioned flavor preference paradigm. Adult male rats with chronic intragastric (IG) cannula were trained to drink a flavored solution (conditioned stimulus; CS+) paired with IG infusion of nutrient solution and another flavored solution (CS−) with IG distilled water infusion on alternate days. The nutrient solution was 60mM monosodium l-glutamate, sodium chloride or glucose. Before and after conditioning, rats received 30min two-bottle choice tests for CS+ and CS− solution. All groups exhibited no significant preference for CS+ in pre-test period. By the last half of conditioning period, intake of CS+ solution was significantly higher than that of CS− in MSG group, but not in NaCl and glucose groups. After conditioned, the MSG group showed significantly higher intake and preference for CS+ solution (69.9%), while the NaCl and glucose group did not show any significant intake and preference for CS+ solution (50.9%, 43.5%, respectively). These results indicate that the amino acid l-glutamate at a preferable concentration has a positive postingestive effect as demonstrated by its ability to condition a flavor preference. The mechanism(s) for this positive effect could be through a direct effect on gut Glu receptors rather than the provision of calories or glucose from metabolized Glu; Further studies are needed to test these hypotheses. [Copyright &y& Elsevier]

Abstract: In the present study, newborn male Wistar rats were injected, subcutaneously, five times, every other day, with monosodium glutamate (MSG, 4g/kg bw) or saline (as control, C), during the neonatal period. MSG animals developed destruction of the arcuate nuclei (ARC) with absence of NPY-immunoreactive cell bodies, which impaired both the food intake (baseline) and the 2-deoxy-d-glucose (2DG) glucoprivic feeding response. Increases in the immunoreactivity of corticotropin-releasing hormone-cell bodies in the paraventricular nuclei might have developed to compensate for the atrophy of the pituitary in MSG-treated rats. After systemic 2DG injection, neither the C nor the MSG rats increased their food intake, but they showed similar hyperglycemic responses, whereas plasma free fatty acids (FFA) increased only in the C group. In other groups, 2DG, norepinephrine (NE), neostigmine (NEO) and saline were intracerebroventricularly (i.c.v.) administered. In this condition, impairment of the hyperglycemic and food intake responses, associated to a lower increase in plasma FFA levels, were observed. As opposed to this, the MSG treatment gives support to NE effects, enhancing food intake, as well as plasma glucose and FFA levels. After NEO, plasma glucose increased only in the MSG group, while plasma FFA levels were elevated in the C rats. Taken together, the results obtained after MSG treatment point to a separate neural control of the hyperglycemic response and of the lipid mobilization when stimulated by central 2DG, NE or NEO administration. It seems likely that the excitatory neural pathway that controls lipid metabolism and is present in C rats was destroyed by the MSG treatment. [Copyright &y& Elsevier]

Neuronal death and lactate dehydrogenase (LDH) activity were evaluated in the cerebral cortices of neonatal rats after exposure to monosodium L-glutamate (MSG) to induce neuroexcitotoxicity. A time–response profile for tumor necrosis factor-alpha (TNF-α) expression was drawn, with measurements taken every 6 h after the first dose of MSG during the first 8 postnatal days, and at days 10 and 14 after birth. An increase in neuronal loss accompanied by high LDH activity and high TNF-α levels was observed at 8 and 10 days. These results indicate that neuronal loss may occur via an apoptosis-like mechanism directed selectively against neurons that express glutamate receptors, mainly the N-methyl-d-aspartate, which it may be strengthen by high TNF-α levels through a feedback mechanism to induce cell death via apoptosis. [Copyright &y& Elsevier]

Monosodium glutamate (MSG) was administered subcutaneously to male neonate rats, and the effects on N-methyl-d-asparatate (NMDA) subunit receptor types NR2C and NR2D from different brain regions were studied. A semi-quantitative reverse transcription-polymerase chain reaction was used to measure NR2C and NR2D expression levels in the cerebral cortex, hippocampus and striatum. MSG treatment (4 mg/g body weight, on postnatal days 1, 3, 5, and 7) produced an important increase of NR2C and NR2D subunit gene expression levels in the hippocampus and striatum of adults rats. No change was observed in the cerebral cortex. We propose that an early excessive activation of glutamate receptors could modify NMDA subunit expression and its structural composition on postnatal development. This, as part of a compensatory response by an altered neuronal circuitry, mainly in the hippocampus and striatum, suggests that the NMDA receptor could be a determinant factor to modulate the dendritic arrangement and the synaptogenesis. [Copyright &y& Elsevier]

• Riluzole protects white matter injury by activation of Nrf2/HO-1 and caspase 9. • Curcumin's neuroprotective effect is mediated through the inhibition of HIF-1α, GFAP, NF-H and caspase 9. • Curcumin is more effective in reducing GFAP and NF-H injury as compared to riluzole. • Combination of riluzole and curcumin is not effective against white matter injury. Damage to the spinal cord (SC) can result in irreversible impairments or complete loss of motor, sensory, and autonomic functions. Riluzole, a sodium channel-blocker and glutamate inhibitor, is in preclinical use for SC injury (SCI), and curcumin is an intracellular calcium inhibitor that attenuates glutamate-induced neurotoxicity. As riluzole and curcumin have different mechanisms to protect against SCI, we aimed to investigate the neuroprotective effects of a combination of riluzole and curcumin in human astrocytes and white matter injury (WMI) model of SCI. Our data show that a combination of riluzole (1 μM) and curcumin (1 μM) was effective in inhibiting hydrogen peroxide (H 2 O 2)-induced oxidative dress in astrocytes derived from human SC, however, curcumin alone showed a significant inhibition. In addition, our results demonstrated that curcumin alone downregulates the hypoxia-induced expression of HIF-1, GFAP, and NF-H proteins in WMI, whereas riluzole alone and in combination with curcumin remained ineffective in changing the expression of these proteins. Contrarily, after inhibiting Ca2+ influx with EGTA, riluzole alone and in combination with curcumin significantly downregulated hypoxia-induced expression of GFAP and NF-H. After analysis of caspase 9 and cleaved caspase 9, we observed that curcumin and riluzole both inhibit apoptosis significantly, whereas their combination remains ineffective. Furthermore, we observed that neuroprotective effects of curcumin and riluzole are mediated through Nrf2/HO-1 signaling. In conclusion, our results demonstrate that curcumin and riluzole protect astrocytes from oxidative stress and white matter from hypoxia. However, their combination is not beneficial to reduce hypoxia-induced astrocytosis, axonal damage, and apoptosis. From our results, it is evident that curcumin is more effective in reducing WMI than riluzole. [ABSTRACT FROM AUTHOR]

• Neonatal monosodium glutamate (MSG)-treatment triggers an excitotoxic process. • MSG-induced neonatal excitotoxic process has lasting effects on the brain. • Astroglial EAATs expression levels are modified by neonatal MSG-treatment. • Changes in EAATs could play an important role in neurodegenerative disorders. Glutamate-mediated excitatory synaptic signalling is primarily controlled by excitatory amino acid transporters (EAATs), such as EAAT1 and EAAT2, which are located mostly on astrocytes and, together, uptake more than 95 % of extracellular glutamate. Alterations in the functional expression levels of EAATs can lead to excessive extracellular glutamate accumulation, potentially triggering excitotoxicity and seizures, among other neurological disorders. Excitotoxicity induced in early developmental stages can lead to lasting changes in several neurotransmission systems, including the glutamatergic system, which could make the brain more susceptible to a second insult. In this study, the expression levels of EAAT1 (GLAST) and EAAT2 (GLT-1) proteins were assessed in the cerebral motor cortex (CMC), striatum, hippocampus and entorhinal cortex (EC) of male adult rats following the neonatal excitotoxic process triggered by monosodium glutamate (MSG)-treatment (4 g/kg of body weight at postnatal days 1,3,5 and 7, subcutaneously). Western blot analysis showed that neonatal MSG-treatment decreased EAAT1 expression levels in the CMC, striatum and hippocampus, while EAAT2 levels were increased in the striatum and EC and decreased in the CMC. Immunofluorescence staining confirmed the changes in EAAT1 and EAAT2 expression induced by neonatal MSG-treatment, which were accompanied by an increase in the glial fibrillary acidic protein (GFAP) immunofluorescence signalthat was particularly significant in the hippocampus. Our results show that a neonatal excitotoxic processes can induce lasting changes in the expression levels of EAAT1 and EAAT2 proteins and suggest that although astrogliosis occurs, glutamate uptake could be deficient, particularly in the CMC and hippocampus. [ABSTRACT FROM AUTHOR]

Dendritic spines are the main postsynaptic neuronal targets of excitatory inputs in cortical neurons, and both spine density and shape possess a well known adaptive synaptic-stimulation-dependent plastic capacity. Eighteen Sprague–Dawley adult male rats were used. Monosodium glutamate-treated rats (4 g/kg of body weight, i.p.) showed tonic and clonic epileptic seizures, as well as less dendritic spines in the apical arborization of their hippocampal CA1 pyramidal cells, compared to both control groups. No changes were seen in the proportional density of thin, stubby, mushroom-shaped, wide, or ramified spines between groups. Excessive glutamate-mediated excitatory activity on receptors could have led dendritic spines to shrink until they disappeared, while the spine-type proportion may be kept balanced as an adaptive response. [Copyright &y& Elsevier]