Impact of Monosodium Glutamate and Corticosterone in the Hippocampus: Glucocorticoid Regulation and Caspase‐3 mediated Microvascular and Neuronal Apoptosis

Abstract

Does monosodium glutamate (MSG) trigger stress circuitry axis and induce apoptosis in the hippocampus? If so, does it mimic the effect of corticosterone (CORT)? In order to test this hypothesis, we put forth a Glutamate model and CORT‐ induced model system in rats to study the modality of glucocorticoid response and apoptotic signaling cascade. 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 an enhanced glucocorticoid receptor (GR) (Nr3c1) gene expression in the hippocampus on day 8, as an immediate response to stress, though not significant. This was followed by a down regulation on day 15 and day 30. Bax, a pro‐apoptotic factor gene showed an insignificant upregulated expression in the hippocampus on day 8, 15 and 30. This indicates the activation of Bax‐ dependent apoptotic pathways at the mRNA level. In the CORT model, GR (Nr3c1) gene expression in the hippocampus showed a very significant downregulation on day 8. Noticed an insignificant activation on day 15 and 30. Bax gene showed a very significant downregulation on day 8, an immediate time point. Day 15 and Day 30 displayed an insignificant up and down regulation. Immunohistochemical analysis revealed the Caspase‐3 mediated death program activation in the microvasculature and neurons of the hippocampus upon MSG and CORT exposure. In the hippocampus field CA1, CA2 and CA3 and dentate gyrus displayed prominent Caspase‐3 immunoreactivity in the microvessels, suggesting potential blood‐brain barrier (BBB) breach. A leaky BBB can transcend vasculotoxic and neurotoxic proteins to invade the brain. Probable events like this can pave way for the neurons and glial cells to be exposed to high levels of glutamate circulating in the blood, which can lead to receptor ‐ mediated neurotoxicity. Neuronal apoptosis is also activated in the hippocampus upon exposure to MSG and CORT. Our results suggest the potential disruption in the brain neural connectivity and neural synchronization upon exposure to MSG and CORT. Recent reports also state that BBB dysfunction and neuronal loss can be attributed and linked to neurodegenerative disorders like Alzheimer’s. Furthermore, MSG mimics the CORT in triggering‐Bax and Caspase dependent apoptotic signaling cascade, to suggest that MSG is a stressor and a neurotoxin. Our results raise concern over the use of MSG as a food additive which needs public awakening and awareness.Support or Funding InformationCUSAT Postdoctoral Fellowship‐Dr. Smita Mathew. U.O. No.Ac. B3/PDF/2016‐17(b) dt. 10.5.2017