Monosodium Glutamate Triggers Neuroendocrine Stress Axis Leading to Apoptosis and Neural Progenitor Cell Activation

Abstract

Can monosodium glutamate (MSG) acts as a stressor and stimulate the hypothalamic‐pituitary‐adrenal (HPA) axis? If so, can its effects be compared to Corticosterone (CORT)? In order to test this hypothesis, we put forth a Glutamate model and CORT induced model system in rats to study the orchestration of molecular signaling pathways. Young adult (2 month old) male Wistar rats weighing about 50–100 g body weight were divided into 4 groups. Group I control rats were injected with saline (NaCl 0.9%) and Group II rats with MSG at a dose of 4 mg/kg body weight. Group III control was ethanol‐saline injected and Group IV was CORT injected at 3 mg/kg body weight. Rats were injected subcutaneously with test materials or vehicles for 7 days and maintained for 8, 15 and 30 days and were sacrificed by decapitation. The MSG model showed significant enhanced Crh gene expression in the hypothalamus as an immediate response to stress. On day 15, the expression level was reduced with a significant increase on day 30. Similarly pituitary Pomc mRNA expression was significantly upregulated on day 8 and 30 with an insignificant downregulation on day 15. GR (Nr3c1) gene expression in the cerebral cortex was significantly upregulated on day 8, a normalization on day 15 and a very significant down regulation on day 30. There was no change in the plasma corticosterone. Caspase‐3 showed an upregulated expression in the hypothalamus on day 8, indicating the activation of Caspase‐3‐dependent apoptotic pathways at the mRNA level. Nestin, a neural stem/progenitor cell marker showed a significant up regulation on day 15 followed by normalized expression on day 30. In the CORT model, Crh gene expression in the hypothalamus showed a significant downregulation on day 8, transient normalization on day 15 and a very significant downregulation on day 30. Pomc mRNA showed a significant downregulation on day 8. GR (Nr3c1) displayed an insignificant downregulation across the three time points. In the CORT group, plasma CORT concentration was not changed significantly across the time points when compared to the control. Nestin gene showed a significant downregulation on day 8. Our results reaffirm that the negative feedback is activated in the CORT model, thereby no cell death and repair. Furthermore, our results raise the question whether there is a shift in the negative feedback mechanism (shut off) activated in MSG‐induced stress? The elevated HPA axis sensitization during the MSG exposure is probably due to impaired negative feedback mechanism or an increased intrinsic excitability of the CRH neurons. This feedback escape may, in turn, attenuate presynaptic glutamate input to the CRH neurons resulting in glutamate neurotoxicity. MSG triggers the apoptotic signaling cascade, thereby causing the neural stem cell to onset repair machinery, to suggest that MSG is a stressor and a neurotoxin.Support or Funding InformationCUSAT Postdoctoral Fellowship‐Dr. Smita Mathew. U.O. No.Ac.B3/PDF/2016‐17(b) dt. 10.5.2017This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.