blz The expression of COX has been correlated

The expression of COX-2 has been correlated with the density of amyloid plaque [65]. A study reported that IMX was effective in suppressing the expression of iNOS and IL-6, but not COX-2, in LPS-stimulated BV2 microglial cells [52]. In this study, IMX did not alter upregulation of COX-2 induced by HFFD. We infer that IMX could attenuate neuroinflammation by blunting GSK-3β/NF-κB signaling without influencing COX-2. Histopathological examination helps in evaluating neuronal damage and drug action. Dark neurons undergoing cytoskeletal and microfilament damage are diagnosed by its hyperbasophilic, hyperargyrophilic and high electron dense properties in histological sections under conditions of oxidative damage [66], diabetes [67], head injuries, ischemia and epilepsy [68]. In this study, we have identified more dark neurons in HFFD mice characterized by nuclear/cytoplasmic condensation with neuronal shrinkage. Further, IMX treatment significantly decreased the formation of dark neurons which clearly indicates its recuperative effects towards neuroapoptosis. In our study, protein expression studies show upregulation of pro-apoptotic Bax protein with concomitant decrease in anti-apoptotic Bcl-2, signifying apoptosis activation in HFFD-fed mice. Our results corroborate with previous reports stating Aβ exposure induce mitochondrial dysfunction [69] and neuronal cell death [70]. Furthermore, in association with activation of GSK-3β in HFFD mice, the increase in Bax expression is correlated with a previous study demonstrating the role of GSK-3β in phosphorylation of Bax to promote neuronal apoptosis [71]. Activation of caspase-3 by Aβ-peptides induces apoptosis and contributes to the pathophysiology of AD [72,73]. Consistent with amyloid deposition, we have also found more number of caspase-3 positive cells in blz of HFFD mice, indicating accomplishment of neuroapoptosis. Previous studies indicate that GSK-3β inhibition by IMX protects neurons from apoptosis [20,51]. In our study, the anti-apoptotic effects of IMX are evident from the attenuation of Bax and caspase-3 expression along with an increase in Bcl-2. These results confirm the role of IMX in preventing intrinsic apoptosis and obviously the suppression of GSK-3β/NF-κB signaling seems to be the upstream event involved. Taken together, we demonstrate that HFFD can induce Aβ-aggregation and neuroinflammation in mice brain. The exact mechanism for these neurodegenerative changes could be attributed by the activation of GS3β/NF-κB signaling. Our results provide robust evidence that HFFD intake for a long time can be a potential risk factor that increases the possibility of neurogenerative diseases such as AD. Hence dietary habits with low calorie foods are recommended. IMX treatment exerts potent neuroprotective effects via inactivation of NF-κB which is synchronized through the inhibition of GSK-3β. Derangements in brain insulin signaling dysregulate metabolic pathways of APP processing [[74], [75], [76]] and hence future studies uncovering the role of IMX on amyloid metabolism are of interest. Pharmacokinetic and toxicity studies with IMX are sparse and hence recommended before initiating clinical trials.
Conflicts of interest
Acknowledgement We gratefully acknowledge the University Grants Commission, New Delhi, India for providing financial assistance to the first author Sathiya Priya C (Senior Research fellow, The Research Fellowship in Sciences for Meritorious Students, UGC-BSR scheme). The authors wish to thank DST-FIST and UGC-SAP for the facilities provided in Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India.
Introduction Growing evidence suggests that local anesthetics, such as lidocaine, bupivacaine, mepivacaine, and ropivacaine, may induce spinal cord neurotoxicity and permanent neurological disorders [1], [2], [3]. Although the overall incidence rate of local anesthetics-induced permanent nerve damage is very low, approximately 0.05‰ [3], [4], one may not ignore the financial, physiological and psychological burdens incurred to individual patients and their families. Therefore, it is critical to decipher the molecular mechanisms underlying spinal cord anesthetic neurotoxicity, in order to provide accurate diagnosis and efficient treatment plans to patients suffered from local anesthetics-induced neurological disorder.