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Full-Text Articles in Medicine and Health Sciences
Novel Olanzapine Analogues Presenting A Reduced H1 Receptor Affinity And Retained 5ht2a/D2 Binding Affinity Ratio, Somayeh Jafari, Marc E. Bouillon, Xu-Feng Huang, Stephen G. Pyne, Francesca Fernandez-Enright
Novel Olanzapine Analogues Presenting A Reduced H1 Receptor Affinity And Retained 5ht2a/D2 Binding Affinity Ratio, Somayeh Jafari, Marc E. Bouillon, Xu-Feng Huang, Stephen G. Pyne, Francesca Fernandez-Enright
Xu-Feng Huang
Background Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios. Results We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors. Conclusions …
Neuregulin-1 Signalling And Antipsychotic Treatment: Potential Therapeutic Targets In A Schizophrenia Candidate Signalling Pathway, Chao Deng, Bo Pan, Martin Engel, Xu-Feng Huang
Neuregulin-1 Signalling And Antipsychotic Treatment: Potential Therapeutic Targets In A Schizophrenia Candidate Signalling Pathway, Chao Deng, Bo Pan, Martin Engel, Xu-Feng Huang
Xu-Feng Huang
Identifying the signalling pathways underlying the pathophysiology of schizophrenia is an essential step in the rational development of new antipsychotic drugs for this devastating disease. Evidence from genetic, transgenic and post-mortem studies have strongly supported neuregulin-1 (NRG1)-ErbB4 signalling as a schizophrenia susceptibility pathway. NRG1-ErbB4 signalling plays crucial roles in regulating neurodevelopment and neurotransmission, with implications for the pathophysiology of schizophrenia. Post-mortem studies have demonstrated altered NRG1-ErbB4 signalling in the brain of schizophrenia patients. Antipsychotic drugs have different effects on NRG1-ErbB4 signalling depending on treatment duration. Abnormal behaviours relevant to certain features of schizophrenia are displayed in NRG1/ErbB4 knockout mice or …
The Role Of Histaminergic H1 And H3 Receptors In Food Intake: A Mechanism For Atypical Antipsychotic-Induced Weight Gain?, Chao Deng, Katrina Western-Green, Xu-Feng Huang
The Role Of Histaminergic H1 And H3 Receptors In Food Intake: A Mechanism For Atypical Antipsychotic-Induced Weight Gain?, Chao Deng, Katrina Western-Green, Xu-Feng Huang
Xu-Feng Huang
Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a lowrisk of extra-pyramidal side-effects. However amajor downfall to their use is metabolicside-effects particularly weight gain/obesity,which occurs by unknownmechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychoticinduced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, andmeta-analyses showa strong correlation between risk ofweight gain andH1 receptor affinity. In addition, olanzapine treatment decreases H1 receptor binding and mRNA expression in the rat …
Effects Of Simvastatin And 6-Hydroxydopamine On Histaminergic H1 Receptor Binding Density In Rat Brains, Chang-Hua Hu, Chao Deng, Nikolce Mackovski, Ling Long, Cansheng Zhu, Yu Yang, Yuge Wang, J-Z Chen, Xu-Feng Huang, Qing Wang
Effects Of Simvastatin And 6-Hydroxydopamine On Histaminergic H1 Receptor Binding Density In Rat Brains, Chang-Hua Hu, Chao Deng, Nikolce Mackovski, Ling Long, Cansheng Zhu, Yu Yang, Yuge Wang, J-Z Chen, Xu-Feng Huang, Qing Wang
Xu-Feng Huang
Statins have been widely used for the treatment of a variety of medical conditions including psychoneurological disorders beyond their original use in lowering cholesterol. Histamine receptors play an important role in the regulation of neural activity, however, it is unknown whether statins act on histamine receptors, particularly for their neural regulatory effects. This study examined the effects of simvastatin and 6-hydroxydopamine (6-OHDA) lesions on histamine H1 receptors using [3H] pyrilamine binding autoradiography. Compared to the saline group, simvastatin (1 mg/kg/day) significantly decreased H1 receptor bindings in the primary motor cortex (M1), ventromedial hypothalamic nucleus (VMH), caudate putamen (CPu), accumbens core …
Increases In Peptide Y-Y Levels Following Oat Β-Glucan Ingestion Are Dose-Dependent In Overweight Adults, Eleanor J. Beck, Linda C. Tapsell, Marijka J. Batterham, Susan M. Tosh, Xu-Feng Huang
Increases In Peptide Y-Y Levels Following Oat Β-Glucan Ingestion Are Dose-Dependent In Overweight Adults, Eleanor J. Beck, Linda C. Tapsell, Marijka J. Batterham, Susan M. Tosh, Xu-Feng Huang
Xu-Feng Huang
Peptide Y-Y (PYY) is an anorexigenic hormone implicated in appetite control, and β-glucan is a fiber known to affect appetite. We hypothesized that plasma PYY levels would increase in overweight human adults consuming increasing doses of β-glucan. The objective was to test whether the effect could be seen with β-glucan delivered through extruded cereals containing a high β-glucan oat bran with demonstrated high molecular weight and solubility. Fourteen subjects consumed a control meal and 3 cereals of varying β-glucan concentration (between 2.2 and 5.5 g), and blood samples were collected over 4 hours. Analysis of raw PYY data showed a …
Distinct Neurobehavioural Effects Of Cannabidiol In Transmembrane Domain Neuregulin 1 Mutant Mice, Leonora E. Long, Rose Chesworth, Xu-Feng Huang, Alexander Wong, Adena Spiro, Iain S. Mcgregor, Jonathon Arnold, Tim Karl
Distinct Neurobehavioural Effects Of Cannabidiol In Transmembrane Domain Neuregulin 1 Mutant Mice, Leonora E. Long, Rose Chesworth, Xu-Feng Huang, Alexander Wong, Adena Spiro, Iain S. Mcgregor, Jonathon Arnold, Tim Karl
Xu-Feng Huang
The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, D9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 …
Oat Β-Glucan Supplementation Does Not Enhance The Effectiveness Of An Energy-Restricted Diet In Overweight Women, Eleanor J. Beck, Linda C. Tapsell, Marijka J. Batterham, Susan M. Tosh, Xu-Feng Huang
Oat Β-Glucan Supplementation Does Not Enhance The Effectiveness Of An Energy-Restricted Diet In Overweight Women, Eleanor J. Beck, Linda C. Tapsell, Marijka J. Batterham, Susan M. Tosh, Xu-Feng Huang
Xu-Feng Huang
Epidemiological evidence shows an inverse relationship between dietary fibre intake and body weight gain. Oat β-glucan, a soluble fibre alters appetite hormones and subjective satiety in acute meal test studies, but its effects have not been demonstrated with chronic consumption. The present study aimed to test the effects in women of two different doses of oat β-glucan on weight loss and hormones associated with appetite regulation. In a 3-month parallel trial, sixty-six overweight females were randomised into one of three 2 MJ energy-deficit diets: a control and two interventions including 5–6 g or 8–9 g β-glucan. Anthropometric and metabolic variables …
Reciprocal Signalling Between Nr2 Subunits Of The Nmda Receptor And Neuregulin 1 And Their Role In Schizophrenia, Amy Geddes, Xu-Feng Huang, Kelly A. Newell
Reciprocal Signalling Between Nr2 Subunits Of The Nmda Receptor And Neuregulin 1 And Their Role In Schizophrenia, Amy Geddes, Xu-Feng Huang, Kelly A. Newell
Xu-Feng Huang
Schizophrenia is a debilitating neurodevelopmental psychiatric disorder. Both the N-methyl-D-aspartate receptor (NMDAR) and neuregulin1 (NRG1) are key molecules involved in normal brain development that have been linked to schizophrenia pathology and aetiology. The NR2 proteins are critical structural and functional subunits of the NMDAR and are developmentally and spatially regulated. Altered NR2 gene and protein expression has been found in human post-mortem schizophrenia brain tissue together with changes in NRG1 and its receptor ErbB4. The NR2 subunits and ErbB4 share a common anchoring domain on the postsynaptic density and therefore a disruption to either of these molecules may influence the …
Reducing Olanzapine-Induced Weight Gain Side-Effect By Using Betahistine: A Study In The Rat Model, Chao Deng, Jiamei Lian, Nagesh Brahmavar Pai, Xu-Feng Huang
Reducing Olanzapine-Induced Weight Gain Side-Effect By Using Betahistine: A Study In The Rat Model, Chao Deng, Jiamei Lian, Nagesh Brahmavar Pai, Xu-Feng Huang
Xu-Feng Huang
Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug’s antagonistic affinity to histamine H1 receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H1 receptor agonist and H3 receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of …
Organization Of Brainstem Nuclei, George Paxinos, Xu-Feng Huang, Gulgun Sengul, Charles Watson
Organization Of Brainstem Nuclei, George Paxinos, Xu-Feng Huang, Gulgun Sengul, Charles Watson
Xu-Feng Huang
This chapter describes human homologs of nuclei identified in the brainstem of other mammals and attempts to extend to the human the overall organizational schemata that have been proposed for the brainstem of other mammalian species. We present herein updated diagrams of the Atlas of the Human Brainstem (Paxinos and Huang, 1995). The diagrams have been thoroughly revised in light of our recent work on the rat (Paxinos and Watson, 2007) and rhesus monkey (Paxinos et al., 3rd ed, in BrainNavigator, Elsevier, 2010) as well as our work on the marmoset (Atlas of the Marmoset Brain in Stereotaxic Coordinates, Paxinos …
Metabolic Parameters And Emotionality Are Little Affected In G-Protein Coupled Receptor 12 (Gpr12) Mutant Mice, Elisabeth Frank, Yizhen Wu, Naomi Piyaratna, William James Body, P Snikeris, Timothy South, Anna-Karin Gerdin, Mikael Bjursell, Mohammad Bohlooly-Y, Leonard H. Storlien, Xu-Feng Huang
Metabolic Parameters And Emotionality Are Little Affected In G-Protein Coupled Receptor 12 (Gpr12) Mutant Mice, Elisabeth Frank, Yizhen Wu, Naomi Piyaratna, William James Body, P Snikeris, Timothy South, Anna-Karin Gerdin, Mikael Bjursell, Mohammad Bohlooly-Y, Leonard H. Storlien, Xu-Feng Huang
Xu-Feng Huang
Background: G-protein coupled receptors (GPR) bear the potential to serve as yet unidentified drug targets for psychiatric and metabolic disorders. GPR12 is of major interest given its putative role in metabolic function and its unique brain distribution, which suggests a role in emotionality and affect. We tested Gpr12 deficient mice in a series of metabolic and behavioural tests and subjected them to a well-established high-fat diet feeding protocol. Methodology/Principal Findings: Comparing the mutant mice with wild type littermates, no significant differences were seen in body weight, fatness or weight gain induced by a high-fat diet. The Gpr12 mutant mice displayed …