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.

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).

Epigenetic Modifications, Alcoholic Brain and Potential Drug Targets.

Acute and chronic alcohol exposure evidently influences epigenetic changes, both transiently and permanently, and these changes in turn influence a variety of cells and organ systems throughout the body. Many of the alcohol-induced epigenetic modifications can contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. The persistence of behavioral changes demonstrates that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype.

Prescribing pattern of analgesics in orthopedic in-patient department at tertiary care hospital in Guwahati, Assam, Northeast India.

Objectives: The aim of this study is to evaluate the prescribing pattern of analgesics and analyze the rational use of analgesic in orthopedic in-patient department of tertiary care teaching hospital, Guwahati, Assam.

Subjects And Methods: An observational and cross-sectional study was carried out for 1 month from April to May 2014. Collected data included age, sex, diagnosis and line of management during the study.

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.

Alternative mechanisms of inhibiting activity of poly (ADP-ribose) polymerase-1.

Poly ADP-ribose polymerase (PARP-1), a DNA nick-sensor enzyme, is an abundant nuclear protein. Upon sensing DNA breaks, PARP-1 gets activated and cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors, and PARP-1 itself. Poly(ADP-ribosylation) mainly contributes to DNA repairing mechanism.

Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1.

Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.

Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days.

Poly (ADP-ribose) polymerase-1 inhibitor, 3-aminobenzamide pretreatment ameliorates lipopolysaccharide-induced neurobehavioral and neurochemical anomalies in mice.

Poly (ADP-ribose) polymerase-1 (PARP-1) functions at the center of cellular stress and sways the immune system at several key points, thus modulates inflammatory diseases. The antiinflammatory properties of PARP-1 inhibitors have been demonstrated ameliorating effect in various neuroinflammatory disorders. It has been reported that there is a close relationship between the inflammatory processes and major depressive disorder.

Targeting poly(ADP-ribose)polymerase1 in neurological diseases: A promising trove for new pharmacological interventions to enter clinical translation.

The highly conserved abundant nuclear protein poly(ADP-ribose)polymerase1 (PARP1) functions at the center of cellular stress response and is mainly implied in DNA damage repair mechanism. Apart from its involvement in DNA damage repair, it does sway multiple vital cellular processes such as cell death pathways, cell aging, insulator function, chromatin modification, transcription and mitotic apparatus function. Since brain is the principal organ vulnerable to oxidative stress and inflammatory responses, upon stress encounters robust DNA damage can occur and intense PARP1 activation may result that will lead to various CNS diseases.