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Fenugreek in Management of Neurological and Psychological Disorders
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Rohini Pujari, Prasad Thakurdesai
Subsequently, IBHB demonstrated therapeutic anti-dyskinetic efficacy against established LID in a separate set of experiments (Thakurdesai, Mohan, Kandhare et al. 2015). In this study, dyskinesia was induced similar to the earlier report (Aswar et al. 2014). However, subacute treatment of IBHB (15, 30, or 60 mg/kg, oral) for the next 45 days was administrated before performing the evaluations for behavioral, biochemical, and ex vivo molecular parameters. Subacute treatment of IBHB demonstrated a dose-dependent reduction in behavioral parameter scores (abnormal involuntary movements (AIMS), grid test, catalepsy bar test, FAS) as compared to the vehicle-treated LID group (Thakurdesai, Mohan, Kandhare et al. 2015). These effects were probably mediated through mechanisms such as restoration of upregulated neurotransmission (serotonin and dopamine turnover and 3-O-Methyldopa levels), immunoreactivity (FosB and 5HT2c), and mRNA expressions (c-FOS, CO-1, Homer-1, Parkin, PDyn, Penk, and PINK1). They downregulated mitochondrial respiratory chain complexes activity and mRNA expression of JunD in the striatum, as shown by ex vivo evaluations on the brain’s striatum area (Thakurdesai, Mohan, Kandhare et al. 2015).
Drugs of Abuse and Addiction
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Aarushi Singh
Continous or acute exposure to any drug leads to induction of all Fos family transcription factors in NAc and other areas of brain. Most of these Fos protein levels come to normal after 8–12 h of exposure except ∆FosB which is a truncated product of a FosB gene (Robison and Nestler, 2012; Nestler, 2013). This product accumulates as it is unusually stable and with course of repeated drug exposure more Fos protein expressed lead to more accumulation. Their stability is to such an expanse that they persist for weeks after drug withdrawal (Nestler, 2013). This chronic induction of ∆FosB is studied almost in every drug and it is established to be more selective for D1-type NAc neurons. It increases an individual’s sensitivity toward the natural and satisfying rewards of drug and promotes self-administration. While CREB induces dynorphin, ∆FosB suppresses it and contribute to pro-reward effects. Functional effects of ∆FosB in other assorted areas of brain are still unrevealed except the orbito frontal cortex (Nestler, 2013). It was found that exposure to cocaine at chronic levels leads to cognitive-disrupting effects which guides to the incidence of ∆FosB-mediated tolerance and this adaptation leads to a rise in cocaine self-administration. Role of ∆FosB in behavioral memory is still under exploration (Nestler, 2013; Robison et al., 2012).
Stimulants and psychedelics
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Genetic variation in a genomic region on chromosome I5q25, which encodes the a5, a3 and b4 subunits of the cholinergic nicotinic receptor genes, confers risk of smoking and nicotine dependence. It also appears that gene cluster-associated variants, which dampen the brain’s response to reward feedback in the right ventral and dorsal anterior cingulate cortex, play a significant role in susceptibility to smoking (Nees et al., 2013). Furthermore, one study has identified 16 single-nucleotide polymorphisms in seven genes that contribute to specific genotypes, and predispose novice adolescent smokers to early smoking and nicotine dependence (O’Loughlin et al., 2014). Regulation of gene expression is also thought to be essential in developing drug addiction, and the transcription factor’s ΔFosB up-regulation may be responsible, at least in part (Nestler, 2013; Ruffle, 2014). Nicotine induces long-term ΔFosB expression in the nucleus accumbens when inhaled or injected at sufficiently high doses, and repeated daily exposure can result in accumbal ΔFosB up-regulation (Marttila et al., 2006; Ruffle, 2014).
Microbiota, not host origin drives ex vivo intestinal epithelial responses
Published in Gut Microbes, 2022
Kaline Arnauts, Padhmanand Sudhakar, Sare Verstockt, Cynthia Lapierre, Selina Potche, Clara Caenepeel, Bram Verstockt, Jeroen Raes, Séverine Vermeire, João Sabino, Catherine Verfaillie, Marc Ferrante
Next, we evaluated direct effects of different types of microbiota on inflamed epithelial cells from UC patients. Exposure to microbiota from UC patients was sufficient to induce damage to the epithelial barrier and activate several stress pathways. Diverse pathways were dysregulated including signaling by NTRK and major activation of RAF/MAP, MAPK signaling and the JAK/STAT pathway following UC microbiota exposure. The top upregulated genes include FOSL1 and FOSB, both belong to the activator protein-1 (AP-1) family, modulated by the MAPK pathway.28 The MAPK pathway activates through phosphorylation specific cellular responses to internal and external stress signals, including phosphorylation of pro-inflammatory proteins, and dysregulation of this pathway is linked to multiple diseases including IBD and tumorigenesis.29–32 Activation of protein kinase inhibitors and regulators was observed after UC microbiota, and is linked to the IBD pathogenesis and microbial processes.31,33 Also, the JAK/STAT pathway is an important therapeutic target in IBD.34 Several of the detected genes are involved in the regulation of intestinal cell apoptosis (ATF335), intestinal barrier function (SPRY4-IT136), inflammation and wound repair (DKK137).
Effects of escalating versus fixed ethanol exposure on ∆FosB expression in the mesocorticolimbic pathway in adolescent and adult rats
Published in The American Journal of Drug and Alcohol Abuse, 2021
Aranza Wille-Bille, Leonardo Marengo, Andrea Godino, Ricardo Marcos Pautassi
∆FosB is part of a family of transcription factors coded by the fos gene (1). These factors heterodimerize with Jun family’s proteins, to form the activator protein AP-1. This complex recognizes specific DNA sites and regulates target gene expression. Unlike other Fos proteins, ∆FosB is very stable and gradually accumulates after repeated stress or drug exposure. Induction of ∆FosB expression in the brain reward areas after chronic and passive, experimenter-administered, exposure to alcohol (2,3), cocaine (4) and other drugs has been reported, a pattern also found in nucleus accumbens core and shell (AcbSh and AcbC, respectively), striatum and prefrontal cortex after chronic ethanol intake (5). These results are consistent with those of Li et al. (6), who observed greater levels of ∆FosB in AcbC and dorsolateral striatum (DLS) after intermittent access to alcohol (further referred to as ethanol). ∆FosB is also observed after chronic stress exposure and its overexpression in the nucleus accumbens increases cocaine-induced appetitive learning, behavioral stimulation and self-administration (7–9). These and other studies (10) suggest that ∆FosB may act as a molecular trigger, promoting initiation and maintenance of drug use (11,12).
Gene fusions in vascular tumors and their underlying molecular mechanisms
Published in Expert Review of Molecular Diagnostics, 2021
Sheena L. M. Ong, Karoly Szuhai, Judith V.M.G. Bovée
As an example, for EH, it has become possible over the past decade to integrate morphology and genetics which has made it clear that EH is highly heterogeneous, both at clinical presentation, at histology [18], and the molecular level. In EH of bone for instance, FOS rearrangements are most common [27] and histology is usually cellular and spindled, especially at the acral sites [18]. Immunohistochemistry for FOS or FOSB can be useful diagnostic tools as a surrogate for molecular testing in these cases, as sometimes it can be very difficult to distinguish the cellular variant from epithelioid angiosarcoma of bone. FOS and FOSB were so far not represented in commercially available NGS fusion panels, and no easily applicable commercial FISH probes are available. However, especially in bone, one should realize that the FOS antibody is vulnerable to decalcification and can give false-negative results, while polysomy can give false-positive results [114], in which case molecular confirmation may be required. In contrast to EH of bone, the ALHE-like variant of EH expresses FOSB in almost all cases [21,22], while at the molecular level no FOSB fusions have been found. The underlying mechanism causing FOSB overexpression in these lesions still remains to be determined. The FOSB overexpression could be a derivative of undiscovered genetic alterations related to the AP-1 complex. Thus, the majority of EH, especially those in soft tissue, do not have FOS or FOSB rearrangement. Recently, FOXO1 rearrangements were detected in a subset of EH lacking FOS or FOSB rearrangement.