Binge alcohol consumption exacerbates high-fat diet-induced neurobehavioral anomalies: Possible underlying mechanisms.

The current study aimed to validate the mice model of alcohol (ALC), high-fat diet (HFD), and HFD + ALC combination affecting neurobehavioral and neurochemical anomalies via inflammatory cascade, lowered neurogenesis, enhanced microgliosis, reactive astrogliosis, activated IDO-1 (indoleamine 2,3-dioxygenase), and reduce CHAT (choline acetyltransferase) signaling in the hippocampus (HIP). The adult male Swiss albino mice were provided with ALC (3-15%) and in-house prepared HFD for continuous 12 weeks. The HFD and HFD + ALC consumption impacted the liver and mediated HIP damage. The liver biomarkers (AST, ALT, γ-GT, TG, HDL-C, and LDL-C), oxidative stress, and proinflammatory cytokines (IL-1ß and TNF-α) level were found significantly higher in the liver and HIP tissue of HFD + ALC. Furthermore, the neurobehavioral deficits that include cognitive dysfunction, depressive, and, anxiety-like behavior were found severely affected in HFD + ALC consumed mice. The overactivated HPA axis, intense oxidative insults, and increased AChE activity were seen in the HIP of HFD + ALC grouped mice. The gene and protein expression also confirmed disrupted NF-κB-mediated inflammatory and Nrf2-regulated antioxidant balance and dysregulated TrκB/BDNF signaling. Hence, our new findings explain the insight mechanism of chronic alcoholism in exacerbating the deleterious effect of chronic high-fat diet consumption on the HIP.

Cognitive deficits induced by combined exposure of stress and alcohol mediated through oxidative stress-PARP pathway in the hippocampus.

Several studies reported that stress can enhance the consumption of alcohol in humans and animals. However, the combinatorial effect of stress and alcohol on cognitive function and neurochemical alterations is quite understudied. In the present study, we have elucidated the involvement of oxidative stress-PARP cascade in alcohol and restraint stress (RS)-exposed animals using a PARP inhibitor, 1,5-isoquinolinediol (3mg/kg for 14days). Male Swiss albino mice were given alcohol (ALC) or RS (2h per day) or both in ALC+RS group for 28days. Behavioral analysis revealed cognitive dysfunction in ALC+RS group. Furthermore, oxidative stress and raised level of pro-inflammatory cytokines were found in the hippocampus region of ALC+RS group. Semi-quantitative reverse transcriptase PCR showed overactivation of PARP-1 gene in ALC+RS group. 1,5-isoquinolinediol treatment significantly prevented cognitive deficits and aforementioned neurochemical alterations. Overall, our findings showed that ALC+RS exerted deleterious effects on the hippocampus which involves oxidative stress-PARP overactivation cascade.

Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.

Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment.

Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1ß and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits.