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Full-Text Articles in Medicine and Health Sciences
A Systematic Review Of The Effect Of Cannabidiol On Cognitive Function: Relevance To Schizophrenia, Ashleigh L. Osborne, Nadia Solowij, Katrina Weston-Green
A Systematic Review Of The Effect Of Cannabidiol On Cognitive Function: Relevance To Schizophrenia, Ashleigh L. Osborne, Nadia Solowij, Katrina Weston-Green
Illawarra Health and Medical Research Institute
Background and objectives Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living. Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored. The aim of this systematic review was to evaluate preclinical and clinical literature on the effects of CBD in cognitive domains relevant to schizophrenia. …
Neurodevelopmental Expression Profile Of Dimeric And Monomeric Group 1 Mglurs: Relevance To Schizophrenia Pathogenesis And Treatment, Jeremy Lum, Francesca Fernandez-Enright, Natalie Matosin, Jessica L. Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell
Neurodevelopmental Expression Profile Of Dimeric And Monomeric Group 1 Mglurs: Relevance To Schizophrenia Pathogenesis And Treatment, Jeremy Lum, Francesca Fernandez-Enright, Natalie Matosin, Jessica L. Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A. Newell
Illawarra Health and Medical Research Institute
Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically …
Molecular Evidence Of Synaptic Pathology In The Ca1 Region In Schizophrenia, Natalie Matosin, Francesca Fernandez-Enright, Jeremy Lum, Martin Engel, Jessica L. Andrews, Nils C. Gassen, Klaus V. Wagner, Mathias V. Schmidt, Kelly A. Newell
Molecular Evidence Of Synaptic Pathology In The Ca1 Region In Schizophrenia, Natalie Matosin, Francesca Fernandez-Enright, Jeremy Lum, Martin Engel, Jessica L. Andrews, Nils C. Gassen, Klaus V. Wagner, Mathias V. Schmidt, Kelly A. Newell
Illawarra Health and Medical Research Institute
Alterations of postsynaptic density (PSD)95-complex proteins in schizophrenia ostensibly induce deficits in synaptic plasticity, the molecular process underlying cognitive functions. Although some PSD95-complex proteins have been previously examined in the hippocampus in schizophrenia, the status of other equally important molecules is unclear. This is especially true in the cornu ammonis (CA)1 hippocampal subfield, a region that is critically involved in the pathophysiology of the illness. We thus performed a quantitative immunoblot experiment to examine PSD95 and several of its associated proteins in the CA1 region, using post mortem brain samples derived from schizophrenia subjects with age-, sex-, and post mortem …
Neuregulin 1 Prevents Phencyclidine-Induced Behavioral Impairments And Disruptions To Gabaergic Signaling In Mice, Martin Engel, Peta Snikeris, Andrew M. Jenner, Tim Karl, Xu-Feng Huang, Elisabeth T. Frank
Neuregulin 1 Prevents Phencyclidine-Induced Behavioral Impairments And Disruptions To Gabaergic Signaling In Mice, Martin Engel, Peta Snikeris, Andrew M. Jenner, Tim Karl, Xu-Feng Huang, Elisabeth T. Frank
Illawarra Health and Medical Research Institute
Background: Substantial evidence from human post-mortem and genetic studies has linked the neurotrophic factor neuregulin 1 (NRG1) to the pathophysiology of schizophrenia. Genetic animal models and in vitro experiments have suggested that altered NRG1 signaling, rather than protein changes, contributes to the symptomatology of schizophrenia. However, little is known about the effect of NRG1 on schizophrenia-relevant behavior and neurotransmission (particularly GABAergic and glutamatergic) in adult animals. Method: To address this question, we treated adult mice with the extracellular signaling domain of NRG1 and assessed spontaneous locomotor activity and acoustic startle response, as well as extracellular GABA, glutamate, and …
Alterations Of Mglur5 And Its Endogenous Regulators Norbin, Tamalin And Preso1 In Schizophrenia: Towards A Model Of Mglur5 Dysregulation, Natalie Matosin, Francesca Fernandez-Enright, Samantha J. Fung, Jeremy S. Lum, Martin Engel, Jessica L. Andrews, Xu-Feng Huang, Cynthia S. Weickert, Kelly A. Newell
Alterations Of Mglur5 And Its Endogenous Regulators Norbin, Tamalin And Preso1 In Schizophrenia: Towards A Model Of Mglur5 Dysregulation, Natalie Matosin, Francesca Fernandez-Enright, Samantha J. Fung, Jeremy S. Lum, Martin Engel, Jessica L. Andrews, Xu-Feng Huang, Cynthia S. Weickert, Kelly A. Newell
Illawarra Health and Medical Research Institute
Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, …
Hypothalamic Ghrelin Signalling Mediates Olanzapine-Induced Hyperphagia And Weight Gain In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-Feng Huang
Hypothalamic Ghrelin Signalling Mediates Olanzapine-Induced Hyperphagia And Weight Gain In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Jiamei Lian, Xu-Feng Huang
Illawarra Health and Medical Research Institute
Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a …
Novel Implications Of Lingo-1 And Its Signaling Partners In Schizophrenia, F Fernandez-Enright, J L. Andrews, K A. Newell, C Pantelis, Xu-Feng Huang
Novel Implications Of Lingo-1 And Its Signaling Partners In Schizophrenia, F Fernandez-Enright, J L. Andrews, K A. Newell, C Pantelis, Xu-Feng Huang
Illawarra Health and Medical Research Institute
Myelination and neurite outgrowth both occur during brain development, and their disturbance has been previously been implicated in the pathophysiology of schizophrenia. Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of axonal myelination and neurite extension. As co-factors of Lingo-1 signaling (Nogo receptor (NgR), With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1)) have been implicated in the genetics of schizophrenia, we explored for the first time the role of Lingo-1 signaling pathways in this disorder. Lingo-1 protein, together with its co-receptor and co-factor proteins NgR, tumor necrosis factor (TNF) receptor orphan Y (TROY), …
Novel Implications Of Lingo-1 And Its Signalling Partners In The Dorsolateral Prefrontal Cortex In Schizophrenia, Jessica L. Andrews, Kelly A. Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Novel Implications Of Lingo-1 And Its Signalling Partners In The Dorsolateral Prefrontal Cortex In Schizophrenia, Jessica L. Andrews, Kelly A. Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Illawarra Health and Medical Research Institute
No abstract provided.
Mapping The Pathophysiology Of Schizophrenia: Interactions Between Multiple Cellular Pathways, Chao Deng, Brian Dean
Mapping The Pathophysiology Of Schizophrenia: Interactions Between Multiple Cellular Pathways, Chao Deng, Brian Dean
Illawarra Health and Medical Research Institute
Schizophrenia is a complex disorder involving dysregulation of multiple pathways in its pathophysiology. Dopaminergic, glutamatergic and GABAergic neurotransmitter systems are affected in schizophrenia and interactions between these receptors contribute to the pathophysiology of the disease. Deficits in acetylcholine muscarinic receptors have been identified in a sub-group of individuals with schizophrenia. Inflammation has also been found to play a major role in the development and exacerbation of psychotic symptoms in schizophrenia. Additionally, evidence from genetic, post-mortem and animal studies over the past decade has identified a number of susceptibility factors for schizophrenia, including neuregulin 1 (Nrg1) and its receptor ErbB4, disrupted-in-schizophrenia-1 …
In Vivo Pharmacological Evaluations Of Novel Olanzapine Analogues In Rats: A Potential New Avenue For The Treatment Of Schizophrenia, Somayeh Jafari, Xu-Feng Huang, Jessica L. Andrews, Francesca Fernandez-Enright
In Vivo Pharmacological Evaluations Of Novel Olanzapine Analogues In Rats: A Potential New Avenue For The Treatment Of Schizophrenia, Somayeh Jafari, Xu-Feng Huang, Jessica L. Andrews, Francesca Fernandez-Enright
Illawarra Health and Medical Research Institute
Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally …
Proteogenomic Analyses Of Lingo-1 And The Nogo Receptor In Schizophrenia, J Andrews, K Newell, F Fernandez
Proteogenomic Analyses Of Lingo-1 And The Nogo Receptor In Schizophrenia, J Andrews, K Newell, F Fernandez
Illawarra Health and Medical Research Institute
No abstract provided.