Behavioural consequences of maternal immune activation (mIA) in rat offspring
Joanna Neill (Manchester Pharmacy School at the University of Manchester)
Lecture C42, Biomedical Sciences Building
Snapshots: Seminars in Physiology, Neuroscience and Pharmacology
Host: Emma Robinson
If you would like to meet with Jo, please contact Emma Robinson (Emma.S.J.Robinson@bristol.ac.uk).
Abstract: Antipsychotic drugs alleviate certain psychotic symptoms of schizophrenia however, cognitive deficit and negative symptoms remain an unmet clinical need (Keefe et al. Arch Gen Psychiatry 2007; 64:633-647). In spite of significant efforts by the Pharmaceutical Industry and academic groups, no drug has yet received a license for these indications (see Talpos, Drug Discov Today, 2017; doi: 10.1016/j.drudis.2017.04.014 for recent review). Several key issues remain unresolved, for example, the failure of positive results with new drug candidates in preclinical to Phase II clinical trials to translate into success in large Phase III trials (Bespalov et al. Nat Rev Drug Discov 2016; 15(7):516) and the impact of long-term antipsychotic drug treatment on brain function. Recent work by Carol Tamminga and colleagues has identified subgroups of patients according to brain based biomarkers not in accordance with their clinical diagnoses (Clementz et al. Am J Psychiatry 2016; 173:373-384). The authors suggest that these subtypes of patients are likely to benefit from differential treatment strategies. The key to development of improved therapies is improved animal models that mimic the human condition in terms of behaviour and pathology and that predict efficacy of novel treatments in patients. The benefit of using animals is development of different models that can represent these separate clinical biotypes, and assessing therapeutic potential of novel and appropriate treatments for each of these. Long-standing research in our laboratory shows that sub-chronic treatment (2 mg/kg ip for 7 days followed by 7 days wash-out) with the un-competitive NMDAR antagonist PCP (Phencyclidine) mimics cognitive and negative symptoms in female Lister Hooded rats, and produces associated pathological changes (Neill et al. Pharmacol & Ther 2010;128(3): 419-432; Neill et al. Eur Neuropsych 2014; 24:822-835). These effects are attenuated by atypical antipsychotics, specifically low dose risperidone and novel targets but not by classical antipsychotics. An emerging project in our laboratory shows that maternal immune activation (mIA) induces pathological and behavioural deficits in the offspring that are sex and time dependent and may represent the developmental trajectory of the illness. Our latest results with the mIA model will be evaluated in this presentation.
Biography: Jo Neill is Professor of Psychopharmacology in the Manchester Pharmacy School at the University of Manchester since January 2013, previously Professor at the University of Bradford. She received a BSc in Pharmacology from the University of Bath in 1986 and a PhD in Psychopharmacology from the University of Birmingham in 1990. Jo worked in the pharmaceutical industry at Merrell Dow and Merck Sharp and Dohme and at the Mario Negri Istituto di Richerche in Milan before moving into academia. She has been conducting research in psychopharmacology for almost 30 years, specifically in the area of development of preclinical models of psychiatric disorders. She has authored over 70 peer-reviewed publications in top scientific journals and is currently the meetings secretary of the British Association for Psychopharmacology, associate editor for Neuroscience Letters and a panel member of the Research Excellence Framework by Higher Education Funding Council for England.
Jo has been conducting research in psychopharmacology for almost 30 years specifically in the areas of drug dependence, ingestive behaviour including mechanisms of antipsychotic-induced weight gain, cognition and schizophrenia, and sex differences in psychopharmacology. Jo’s expertise is in development and validation of preclinical models of psychiatric disorders. Most recently she is collaborating on research projects investigating cognitive function and cognitive remediation therapy in ADHD and 1st episode psychosis patients and effects of gonadal steroids on cognitive function across pregnancy. Jo has developed and refined a preclinical model and several tests of cognitive deficit and negative symptoms in schizophrenia for evaluation of novel targets and identification of translational biomarkers, in collaboration with Michael Harte, who has also just re-located to Manchester. The has led to establishment of a University based CRO, b-neuro (b-neuro.com) Jo’s research team currently consists of 4 full-time PhD students (with 3 new PhDs to start in 2013) 2 research technicians and a laboratory manager and post-doctoral researcher. We present our latest findings at 5 conferences (on average) per year. Collaborations with several major competing Pharmaceutical Companies including GSK (2001-2011) Lundbeck, Janssen (J&J), Forest, Merz, Takeda, Eisai, Roche, Abbott and leading academics in the US, Europe and UK. Key Opinion Leader for new psychiatric drugs for Servier, Roche and Organon. Speaker for ESSWAP since 2005 (European Summer School for Whole Animal Pharmacology, Netherlands). Jo has organized symposia at National and International conferences regularly since 2010 and makes frequent International platform presentations to present her research work. Jo’s most recent research work is developing preclinical models of ADHD, Alzheimer’s disease and refining tests of negative symptoms in schizophrenia.
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