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Derek Costello

Lecturer/Assistant Professor

School Of Biomolecular & Biomed Science
Conway Institute
Belfield
Dublin 4

Tel: 353 1 716 6775
Email: derek.costello@ucd.ie

Biography

Jan 2015 - date:      University College Dublin
Lecturer, Neuroscience  |  UCD School of Biomolecular & Biomedical Science 


Oct 2008 - Dec 2014:      Trinity College Dublin
Research Fellow: Cellular Neuroscience & Neuroinflammation  |  Department of Physiology & Trinity College Institute of Neuroscience
Principal Investigator: Prof. Marina A. Lynch                                         


May 2004 - Sept 2008:      University College London
Postdoctoral Research Fellow: Cellular Neurophysiology  |  Department of Physiology 
Principal Investigator: Prof. Paola Pedarzani


Oct 2003 - April 2004:      University College Dublin
Teaching Assistant  |  Department of Physiology

Research Links:  SBBS Research  |  Mechanisms of Disease (Neuroscience) Research in SBBS 

Professional

 

Associations

Association: British Neuroscience Association, Function/Role: Member/Local Group Representative (Ireland)
Association: Neuroscience Ireland, Function/Role: Treasurer
Association: Physiological Society, Function/Role: Member
Association: British Pharmacological Society, Function/Role: Member
Association: Society for Neuroscience (USA), Function/Role: Member
     

Conference Contributions

Fernandez-Perez, I., Britchfield, C., Al-Abdullah, F. & Costello, D.A. (2016) Amyloid-β-mediated hippocampal epileptogenesis is facilitated by TLR2 activation. Young Neuroscience Symposium (2016), Trinity College Dublin .
Duffy, C.P., Howe, A-M, McGillicuddy, F.C. & Costello, D.A. (2016) Investigating obesity-induced susceptibility to Alzheimer's disease-related inflammation. Young Neuroscience Symposium (2016), Trinity College Dublin .
Duffy, C.P., Howe, A-M. & Costello, D.A. (2016) Monounsaturated fats alleviate the obesity induced susceptibility to Alzheimer¿s disease-related inflammation. UCD Conway Festival of Research & Innovation (2016), .
Howe, A-M, McGillicuddy, F.C & Costello, D.A. (2016) Investigating the influence of dietary fats on inflammatory changes in the brain. UCD Conway Festival of Research & Innovation (2016), .
Fernandez-Perez, I., Britchfield, C., Al-Abdullah, F. & Costello, D.A. (2016) TLR2 activation promotes amyloid-β-mediated hippocampal epileptogenesis. UCD Conway Festival of Research & Innovation (2016), .
Moore, S.P., O'Reilly M., McGillicuddy F. & Costello, D.A. (2015) Monounsaturated fats alleviate obesity-induced changes in the brain. UCD Conway Festival of Research & Innovation (2015), .
   

Education

Year 2004 Institution: University College Dublin
Qualification: PhD Subject:
Year 2000 Institution: University College Dublin
Qualification: BSc. (Hons) Subject: Physiology
         

Publications

 

Book Chapters

Herron, CE; Costello, DA (2017) 'Alzheimer's, Neuroinflammation and the Endocannabinoid System' In: Kelly, MEM; Lehmann, C; Zhou, J (eds). The Endocannabinoid System in Local and Systemic Inflammation. USA: Morgan & Claypool. [DOI] [Details]
 

Peer Reviewed Journals

D.A. Costello, K. Keenan, R.M. McManus, A. Falvey & M.A. Lynch (2016) 'The age-related neuroinflammatory environment promotes macrophage activation, which negatively impacts synaptic function'. Neurobiology of Aging, 43 :140-148. [DOI] [Details]
D.A. Costello, D.G. Carney, M.A. Lynch (2015) 'α-TLR2 antibody attenuates the Aβ-mediated inflammatory response in microglia through enhanced expression of SIGIRR'. Brain, Behavior, and Immunity, 46 :70-79. [DOI] [Details]
J.P. Barrett, D.A. Costello, J. O'Sullivan, T.R. Cowley & M.A. Lynch (2015) 'Bone marrow-derived macrophages from aged rats are more responsive to inflammatory stimuli'. Journal of Neuroinflammation, 12 (67). [DOI] [Details]
D.A. Costello & M.A. Lynch (2013) 'Systemic toll-like receptor 3 activation modulates hippocampal network excitability, via glial production of interferon-β'. Hippocampus, :696-707. [DOI] [Details]
R.J. Kelly, A.M. Minogue, A. Lyons, R.S. Jones, T.C. Browne, D.A. Costello, S. Denieffe, C. O'Sullivan, T.J. Connor & M.A. Lynch (2013) 'Glial activation in APP/PS1 mice is associated with infiltration of IFNγ-producing cells'. Journal of Alzheimer's Disease, 37 (1):63-75. [DOI] [Details]
A. Lyons, E.J. Downer, D.A. Costello, N. Murphy & M.A. Lynch (2012) 'Dok2 mediates the CD200Fc attenuation of Aβ-induced changes in glia'. Journal of Neuroinflammation, . [DOI] [Details]
D.A. Costello, M. Claret, H. Al-Qassab, F. Plattner, E.E. Irvine, A.I. Choudhury, K.P. Giese, D.J. Withers & P. Pedarzani (2012) 'Brain deletion of Insulin Receptor Substrate type-2 disrupts hippocampal synaptic plasticity and metaplasticity'. PLoS ONE, . [DOI] [Details]
D.A. Costello*, A. Lyons*, S. Denieffe, T.C. Browne, F.F. Cox & M.A. Lynch (2011) 'Long-term potentiation is impaired in membrane glycoprotein CD200-deficient mice: a role for TLR activation'. Journal of Biological Chemistry, . [DOI] [Details]
D.A. Costello, M.B. Watson, T.R. Cowley, N. Murphy, C. Murphy Royal, C. Garlanda & M.A. Lynch (2011) 'IL-1alpha and HMGB1 mediate hippocampal dysfunction in SIGIRR-deficient mice'. Neuroscience, . [DOI] [Details]
M.B. Watson, D.A. Costello, D.G. Carney, K. McQuillan & M.A. Lynch (2010) 'SIGIRR modulates the inflammatory response in the brain'. Brain, behavior, and immunity, . [DOI] [Details]
D.A. Costello, D.M. O'Leary & C.E. Herron (2005) 'Agonists of peroxisome proliferator activated receptors can attenuate the Abeta-mediated impairment of LTP and may modulate synaptic transmission and plasticity in the hippocampus'. Neuropharmacology, . [Details]
D.A. Costello & C.E. Herron (2004) 'The role of c-Jun N-terminal kinase in the A beta-mediated impairment of LTP and regulation of synaptic transmission in the hippocampus'. Neuropharmacology, . [Details]
D.B. Freir, D.A. Costello & C.E. Herron (2003) 'A beta[25-35] induced depression of long-term potentiation in area CA1 in vivo and in vitro is attenuated by Verapamil'. Journal of Neurophysiology, . [Details]
 

Conference Publications

Costello, D.A. & Lynch, M.A. (2012) SLAM (CD150) functions as an inflammatory modulator in the brain Journal of Neuroimmunology 253 (1-2): 93-93 (2012) [Details]
Costello, D.A., Watson, M.B., Cowley, T.R., Murphy, N., Murphy Royal, C., Garlanda, C. & Lynch, M.A. (2011) IL-1α and HMGB1 mediate hippocampal dysfunction in SIGIRR-deficient mice Dublin Region Higher Education Alliance Workshop: ¿Cytokines in the Brain: the good, the bad and the ugly¿ [Details]
Costello, D.A., Watson, M.B. & Lynch, M.A. (2009) Deficiency in SIGIRR leads to impairment of synaptic plasticity and hippocampal¿dependent memory Irish Journal of Medical Science, Vol. 179, S115 (2009) [Details]
Costello, D.A., Watson, M.B. & Lynch, M.A. (2009) Investigating hippocampal-dependent memory and synaptic function in Single Ig-like IL-1 Related Receptor deficient mice 39th Annual Meeting of the Society for Neuroscience, 424.9 (2009) [Details]
Costello, D.A., Al-Qassab, H., Irvine, E.E., Giese, K.P., Withers, D.J. & Pedarzani, P. (2007) Effects of Insulin Receptor Substrate type-2 deficiency on neuronal excitability and synaptic plasticity in the hippocampus 37th Annual Meeting of the Society for Neuroscience, 473.5 (2007) [Details]
Costello, D.A., Jones, M.R., Richards, C.D. & Pedarzani, P. (2006) Mechanisms underlying the calcium-dependent activation of an afterdepolarising current in hippocampal CA1 neurons 36th Annual Meeting of the Society for Neuroscience, 342.25 (2006) [Details]
Costello, D.A. & Herron, C.E. (2004) Agonists of peroxisome proliferator activated receptor-γ attenuate the beta-amyloid mediated impairment of long-term potentiation Journal of Physiology, 555P: C43 (2004) [Details]
Costello, D.A. & Herron, C.E. (2003) Role of c-Jun-N-terminal kinase in β-amyloid mediated impairment of long-term potentiation 33rd Annual Meeting of the Society for Neuroscience, 690.8 (2003) [Details]
Schmid, A.W., Herron, C.E., Costello, D.A. & Freir D.B. (2003) Aβ-mediated depression of hippocampal synaptic plasticity: mechanism of action? Journal of Physiology, 551P: SA6 (2003) [Details]
Costello, D.A. & Herron, C.E. (2003) Involvement of c-Jun-N-terminal kinase in beta-amyloid mediated impairment of long-term potentiation in the hippocampal CA1 in vitro Journal of Physiology, 547P: PC26 (2003) [Details]
Costello, D.A. & Herron, C.E. (2002) Interaction of L-type calcium channel blockers and ABeta[25-35] on long term potentiation in the hippocampal CA1 in vitro Pflugers Archiv: European Journal of Physiology, vol. 443s, 299P (2002) [Details]
Costello, D., Minogue, A., Freir, D., Schmid, A., Lynch, M. & Herron, C. (2002) β-amyloid peptide induces phosphorylation of stress activated kinase JNK and depresses LTP in the hippocampal CA1 region in vitro and in vivo Proceedings of Federation of European Neuroscience Societies (3rd Forum), 151.5 (2002) [Details]
                                                                                                                                       

Research

Research Interests

My research examines the physiological mechanisms which underlie dysfunction of learning, memory and executive brain function. Investigating the complex cellular processes regulating neuronal excitability and synaptic properties, using a multi-disciplinary approach, has enabled me to assess how disruption of these systems may occur in neurological and neurodegenerative disorders. Assessment and modulation of the integrity of the brain's endogenous immunological system has provided insight into the pathological mechanisms which may induce or augment the progression of neuroinflammatory, neuroimmunological and neurodegenerative conditions. My experimental techniques and specific research interests are summarised below.
 
 

Experimental Techniques

Electrophysiology (in vitro) - Extracellular and whole-cell patch-clamp recording from acute and cultured brain slices (including knockout and transgenic animals) and primary cultured neurons

Biochemical analyses - Standard methods including Western immunoblot assay, enzyme-linked immunosorbent assay and real-time PCR analysis

Imaging analysis - Live-cell, 2-photon fluorescent microscopy on brain slices and primary neuronal cultures (including simultaneous patch-clamp recording)

Behavioural analysis - Analysis of hippocampal-dependent learning

Biological preparations - Acute and organotypic hippocampal slices, primary neuronal cultures, primary microglial and astrocytic cultures, and isolated bone marrow-derived macrophages from rodents.

 

Research Summary

Neuroinflammation and immunoregulation

Neurological and neurodegenerative conditions, including Alzheimer¿s disease and Multiple Sclerosis, are associated with inflammatory changes in the brain. The complex interaction between microglia, the resident immune cells of the brain, and neuronal circuitry becomes dysfunctional in disease states. My work has illustrated that harnessing the benefits of the endogenous immuno-protective mechanisms of the brain may provide a potential avenue for therapeutic intervention into inflammatory-related neurodegenerative disease.

  • Assessed the role of key immune modulatory proteins in brain dysfunction associated with inflammatory insult, using pharmacology and genetically-modified animals.
  • Employed a variety of electrophysiological, biochemical and behavioural analyses to provide insight into the essential involvement of immune modulators and regulatory proteins in maintaining brain function.       

See: Costello et al., Brain Behav Immunity (2015); Costello et al., J Neurosci (2011); Costello et al., J Biol Chem (2011)
 
Ion channel physiology and neuronal excitability

Maintaining cellular and electrical homeostasis of neurons is integral to regular brain function. Conditions such as epilepsy arise due to profound dysregulation of neuronal circuitry. I have investigated the cellular mechanisms which control the activity of neurons. Understanding these mechanisms enables us to identify the potential irregularities which may disrupt neuronal function under pathological conditions.

  • Assessed the calcium-mediated regulation of neuronal activation using a combination of electrophysiology and fluorescent microscopy.
  • Investigated the dynamic interplay between calcium-sensitive ionic conductances in hippocampal neurons at a cellular level, to further characterise the mechanisms which underlie the regulation and maintenance of neuronal circuitry.        
  • Investigated the modulation of hippocampal excitability in response to the immune challenge imposed by systemic administration of a viral mimetic.     

See: Costello & Lynch, Hippocampus (2013); Giovannini, Costello et al., (in preparation)
 
Insulin-mediated regulation of neuronal function

Incidences of cognitive dysfunction are strongly correlated with diabetes. Research in this area has been compromised due to the confounding factors associated with the peripheral symptoms of glucose intolerance. My research identified the essential role of insulin-mediated signalling in the brain, which maintains the characteristic neuronal activity associated with memory formation.

  • Collaboration with an endocrinology, cognitive and electrophysiological research group.
  • Investigated the impact of insulin-mediated signal transduction on cellular function in the brain.
  • Used a genetically-modified mouse model, with brain-specific deletion of an insulin signalling molecule
  • Identified a critical role for this pathway in the synaptic processes believed to play a role in executive cognitive function.      
See: Costello et al., PLoS One (2012)

Research Projects

Sponsor : University College Dublin (UCD)
Title : Principal Investigator Starting Award
Start Date / End Date : 05-JAN-15 / 30-JUN-18
Sponsor : The Wellcome Trust (WT)
Title : To investigate the impact of dietary fats on Alzheimer's diseaserelated inflammatory changes
Start Date / End Date : 01-JUN-16 / 31-AUG-16
Sponsor : University College Dublin (UCD)
Title : To investigate the effects of bacterial agents on Alzheimer¿s disease-related neuroinflammation.
Start Date / End Date : 24-MAY-16 / 30-JUN-17
   

Collaborators

Internal Collaborators

  • Assoc. Prof. Caroline Herron. UCD School of Biomolecular and Biomedical Science, University College Dublin
  • Dr. Fiona McGillicuddy. Asst. Prof. & Wellcome Trust Investigator. UCD School of Medicine, University College Dublin
  • Assoc. Prof. John Crean. UCD School of Biomolecular and Biomedical Science, University College Dublin
  • Assoc. Prof. Orina Belton. UCD School of Biomolecular and Biomedical Science, University College Dublin
  • Dr. Alison Reynolds. Asst. Prof. UCD School of Veterinary Medicine, University College Dublin

 

External Collaborators

  • Prof. Marina Lynch, Professor of Cellular Neuroscience, Department of Physiology, Trinity College Dublin
  • Prof. Dominic J. Withers. Clinical Chair in Diabetes & Endocrinology. Institute of Clinical Science, Imperial College London, UK.
  • Dr. Cecilia Garlanda. Laboratory of Experimental Immunopathology. Istituto Clinico Humanitas, Milan, Italy
  • Prof. Chris D. Richards. Emeritus Professor of Experimental Physiology. Faculty of Life Sciences, University College London, UK.
  • Dr. Raffaella Tonini. Team Leader. Cellular Neurophysiology, Division of Neuroscience & Brain Technologies. Italian Institute of Technology, Genoa, Italy.
  • Prof. Padraic G. Fallon. Professor of Translational Immunology. Institute of Molecular Medicine & School of Medicine, Trinity College Dublin.
  • Prof. Kingston H. G. Mills. Professor of Immunology. Immunology Research Centre, School of Biochemistry & Immunology, Trinity College Dublin.