Dr P Chazot, BSc (Hons) ARCS PhD
My research group focuses on the identification, characterisation and validation of novel drug targets for the treatment of the major acute and chronic CNS pathologies.
Major Research Roles:
Integrative Neuroscience Group (Co-founder & Coordinator)
ESF COST BMO 806 Management Committee (2008-2012)
The European Histamine Research Society (Elected Council Officer, 2006-2009)
British Neuroscience Association (Elected Council Officer, 2008-2011)
Neuroscience North East Conference (Founder and organiser, 2000-present day)
Some key publications since 2001:
1. van Rensburg R, Errington DR, Ennaceur A, Lees G, Obrenovitch TP, Chazot PL (2008)A new model for the study of high-K(+)-induced preconditioning in cultured neurones: Role of N-methyl-d-aspartate and alpha7-nicotinic acetylcholine receptors.
J Neurosci Methods. 2008 Oct 21. [Epub ahead of print]
2. Ennaceur A, Michalikova S, Chazot PL (2008) Do rats really express neophobia towards novel objects? Experimental evidence from exposure to novelty and to an object recognition task in an open space and an enclosed space.
Behav Brain Res. 2008 Oct 15. [Epub ahead of print]
3. Huang L, Abuhamdah S, Howes MJ, Elliot MS, Ballard C, Holmes C, Burns A, Perry EK, Francis PT, Lees G, Chazot PL (2008)Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.
J Pharm Pharmacol. 2008 Nov; 60(11):1515-22.
4. Ennaceur A, Michalikova S, van Rensburg R, Chazot PL (2008)Detailed analysis of the behavior and memory performance of middle-aged male and female CD-1 mice in a 3D maze.
Behav Brain Res.87(2):312-26.
5. Michalikova S, Ennaceur A, van Rensburg R, Chazot PL (2008)Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: Effects of low infrared light.
Neurobiol Learn Mem. 89(4):480-8.
6. A. Ennaceur, S. Michalikova, R. van Rensburg and P.L. Chazot (2008) Are Benzodiazepines Really Anxiolytic? Evidence from a 3D maze spatial navigation task.
Behavioural Brain Research. 188(1):136-53.
7.Morini G, Becchi G, Shenton FC, Chazot PL, Grandi D.Histamine H3 and H4 receptors are expressed on distinct endocrine cell types in the rat fundic mucosa.
Inflamm Res. 2008;57 Suppl 1:S57-58
8. van Rijn RM, van Marle A, Chazot PL, Langemeijer E, Qin Y, Shenton FC, Lim HD, Zuiderveld OP, Sansuk K, Dy M, Smit MJ, Tensen CP, Bakker RA, Leurs R (2008)
Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor.
Biochem J. 15;414(1):121-31.
9. Grandi D, Shenton FC, Chazot PL, Morini G.(2008)Immunolocalization of histamine H3 receptors on endocrine cells in the rat gastrointestinal tract.
Histol Histopathol. 23(7):789-98.
10. Bäumer W, Wendorff S, Gutzmer R, Werfel T, Dijkstra D, Chazot P, Stark H, Kietzmann M. (2008) Histamine H4 receptors modulate dendritic cell migration through skin - immunomodulatory role of histamine.
11. Abuhamdah S, Huang L, Elliott MS, Howes MJ, Ballard C, Holmes C, Burns A, Perry EK, Francis PT, Lees G, Chazot PL (2008)Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.
J Pharm Pharmacol. 2008 Mar;60(3):377-84.
12. Dijkstra D, Stark H, Chazot PL, Shenton FC, Leurs R, Werfel T, Gutzmer R.Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor.
J Invest Dermatol. 128(7):1696-703
13. Dijkstra D, Leurs R, Chazot P, Shenton FC, Stark H, Werfel T, Gutzmer R. (2007) Histamine downregulates monocyte CCL2 production through the histamine H(4) receptor.
J Allergy Clin Immunol.120(2):300-7.
14. Cannon KE, Chazot PL, Hann V, Shenton F, Hough LB, Rice FL(2007)Imunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: potential antinociceptive targets.
15. PL Chazot (2007) Safinamide for the treatment of Parkinson's disease, epilepsy and restless legs syndrome.
Curr Opin Investig Drugs. 2007 Jul;8(7):570-9.
16. RM Van Rijn*, PL Chazot*, FC Shenton, RA Bakker and R Leurs (2006) Oligomerisation of recombinant and endogenously expressed human H4 histamine receptors (* joint first authors)
Mol. Pharmacol. 70(2):604-15.
17. Ennaceur A, Michalikova S, van Rensburg R, Chazot PL. (2006) Models of anxiety: Responses of mice to novelty and open spaces in a 3D maze.
Behav Brain Res. 174(1):9-38.
18. Bakker RA, Lozada AF, Marle AV, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM, Chazot PL, Panula P, Leurs R(2006) Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant negatives
Mol. Pharmacol. 69, 1194-1206.
19. Ennaceur A, Michalikova S and Chazot PL (2006) Models of anxiety: responses of rats to novelty in an open and enclosed space.
Behav Brain Res 171(1):26-49.
20. Abuhamdah, S, Fuerstner, A, Lees, G and Chazot, PL (2005) Pharmacological binding studies of caloporoside and novel congeners with contrasting effects upon [35S] TBPS binding to mammalian GABA-A receptor.
Biochem. Pharmacol. 70, 1382-8.
21. Chazot PL (2004)The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies.
Curr Med Chem. 11(3):389-96.
22. Rezai N, Duggan C, Cairns D, Lees G, Chazot PL (2003) Modulation of [3H] TBOB binding to the rodent GABAA receptor by simple disaccharides.
Biochem Pharmacol. 65(4):619-23.
23. PL Chazot, OV Godukhin, A McDonald and TP Obrenovitch. (2002) Spreading Depression-induced preconditioning in the mouse cortex: Differential changes in the protein expression of ionotropic nicotinic acetylcholine and glutamate receptors.
J. Neurochem. 83 1235-1238.
24. PL Chazot, S Lawrence and CL Thompson. (2002)Studies on the subtype selectivity of CP-101,606: evidence for two classes of NR2B-selective NMDA receptor antagonists.
Neuropharmacology 42, 319-324
25. CL Thompson, DL Drewery, HD Atkins, FA Stephenson and PL Chazot. (2002) Immunohistochemical localisation of NMDA receptor subunits in the mammalian hippocampal formation: Evidence for a unique role for the NR2D subunit.
Molecular Brain Res. 102, 55-61.
26. Beck M, Brickley K, Wilkinson HL, Sharma S, Smith M, Chazot PL, Pollard S, Stephenson FA (2002)Identification, molecular cloning and characterization of a novel GABAA receptor-associated protein, GRIF-1.
J Biol Chem. 16;277(33):30079-90.
27. Obrenovitch TP, Godukhin OV, Chazot PL (2002) Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?
Neurosci Lett. 8;320(3):161-3.
28. Chazot PL, Hann V (2001) Overview: H3 histamine receptor isoforms: new therapeutic targets in the CNS?
Curr Opin Investig Drugs. 2, 1428-31.
29. Chazot PL, Hann V, Wilson C, Lees G, Thompson CL (2001) Immunological identification of the mammalian H3 histamine receptor in the mouse brain. Neuroreport. 12, 259-62.
There are five integrative strands to my overall research programme:
1. NMDA glutamate receptor subtypes: We use recombinant NMDA receptors expressed in cell lines, and native radioligand binding/ligand autoradiographical approaches to define the selectivity and mode of action of novel NMDA receptor ligands. We then use these ligands to define the importance of defined subtypes in epilepsy (in vitro cortical slice model), synaptic plasticity (in vitro hippocampal slice model), learning and memory animal models, chronic pain, human Parkinson’s disease and Dementia with Lewy Bodies (ligand autoradiography/immunohistochemistry), the latter focussed on correlations to cognitive, psychotic and movement deficits, particularly dyskinesias.
2. Histamine receptor subtypes; My group has developed the first immunological probes for the human H3 and H4 histamine receptor subtypes, which we have used together with novel pharmacological ligands to biochemically determine the molecular structure of these new subtypes of histamine receptor. We have also defined the anatomical framework for the role of the H3 receptor in mechanical nociception and the GI tract, and we are currently mapping the H3 receptor in the human brain, particularly in the basal ganglia and cortical regions. We are particularly interested in the heteroreceptor role of the H3 receptor in controlling the GABA-ergic system. We are currently assessing the role of the H3 receptor in learning and memory and anxiety, using novel H3 receptor ligands, and new validated animal behavioural models. We have provided the first evidence for the presence of the histamine H4 receptor in the human and rodent brain.
3. GABA-A receptors We are interested in identifying and modelling new GABA-A receptor ligands. We have identified a number of candidate novel GABA-A receptor chemical classes (many based on natural products) using our in vitro pharmacological screens, which we are currently confirming using functional, and behavioural screens (animal studies and human clinical trials (agitation in late-stage AD patients).
4. Preconditioning: We are using the brain’s natural ability to protect itself in adverse conditions to identify novel neuroprotection strategies. We have a series of in vitro pharmacological (primary cortical neurons in culture) and in vivo physiological (repetitive cortical spreading depression model) preconditioning models. This strategy has identified candidate proteins which may underlie this long term neuroprotection. We are assessing the role of these candidate proteins, by increasing (adenoviral transgene) or reducing (antisense) protein expression, respectively, with end points including neuroprotection, amyloid load/plaques, chemokine activation and behavioural recovery (learning and memory)in an in vivo AD transgenic mouse model.
5. We have developed the first validated animal models for human anxiety. We are currently using our all-in-one anxiety-learning-memory models to delineate the anatomical and molecular basis underpinning emotional and cognitive human behaviours. These models could become the gold-standards for future CNS drug development and genetic phenotyping.
- Biomedical Sciences Admissions Tutor
- Biological and Biomedical Sciences Library Tutor
- Industrial Placement Tutor
- Hatfield College Council Officer & Tutor
- President - North Durham Parkinson's Disease Society Branch
- External Examiner - Biomedical Sciences,Pharmacology & Intercalated Medical Degrees (University of Bradford)
Previous Academic Roles:
- Module Leader Pharmacology
- Module Leader Neuroscience
- Pharmacology co-ordinator Phase 1 Medicine
- Dr Fiona Cameron Shenton
- Mr. Simon C. Cork
- Mr Rushdie Abuhamdah
- Miss Natalie Duggett
- Miss Mwape Katebe
- Mr Max Brown
- Mrs Sarah Cartwright
- Dr Chazot’s group is interested in identifying, studying and validating novel drug targets for treating acute brain damage and a range of common chronic neuropathologies
- Further technologies available through collaborations: in vitro electrophysiology (culture, slice), in vivo behavioural (learning/memory; anxiety)
- Recent expertise in the lab include Primary neuronal cell cultures, in vitro and in vivo hypoxia and ischaemia models, volatile anaesthetic preconditioing model
- Technologies employed include immunobiochemistry, molecular biology, ligand autoradiography, radioligand binding, heterologous expression, adenoviral transfection
Journal papers: academic
- Wang M, Chazot PL, Ali S, Duckett SF & Obrenovitch TP (2012). Effects of NMDA receptor antagonists with different subtype selectivities on retinal spreading depression. British Journal of Pharmacology 165(1): 235-244.
- Ennaceur A, Michalikova S, van Rensburg R & Chazot PL (2011). MK-801 increases baseline level of anxiety in mice introduced to a spatial memory task without prior habituation. Neuropharmacology 61(5-6): 981-991.
- van Rensburg, R, Errington, DR, Ennaceur, A, Lees, G, Obrenovitch, TP & Chazot, PL (2009). A new model for the study of high-K(+)-induced preconditioning in cultured neurones: role of N-methyl-d-aspartate and alpha7-nicotinic acetylcholine receptors. Journal of Neuroscience Methods 177(2): 311-316.
- Ennaceur, A. Michalikova, S. & Chazot, P.L. (2009). Do rats really express neophobia towards novel objects? Experimental evidence from exposure to novelty and to an object recognition task in an open space and an enclosed space. Behavioural Brain Research 197: 417-434.
- Connolly, W, Shenton, FC, Lethbridge N, Leurs R, Waldvogel HJ, Faull RLM, Lees G & Chazot PL (2009). The histamine H4 receptor is functionally expressed on neurons in the mammalian CNS. British Journal of Pharmacology 157(1): 55-63.
- Dijkstra, D., Stark, H., Chazot, P.L., Shenton, F.C., Leurs, R., Werfel, T. & Gutzmer, R. (2008). Human inflammatory dendritic epidermal cells (IDEC) express a functional histamine H4 receptor. Journal of Clinical and Investigative Dermatology 128: 1696-1703.
- Van Rijn, RM., Chazot, PL., Shenton, FC., Sansuk, K., Bakker, RA. & Leurs, R. (2006). Oligomerization of recombinant and endogenously expressed human histamine H4 receptors. Molecular Pharmacology 70(2): 604-615.
- Abuhamdah, S., Fuerstner, A., Lees, G. & Chazot, PL. (2005). Radioligand binding studies of caloporoside and novel congeners with contrasting effects upon [35S] TBPS binding to the mammalian GABAA receptor. Biochemical Pharmacology 70(9): 1382-1388.
- Chazot, PL., Godukhin, OV., McDonald A. & Obrenovitch, TP. (2002). Spreading Depression-induced preconditioning in the mouse cortex: Differential changes in the protein expression of ionotropic nicotinic acetylcholine and glutamate receptors. Journal of Neurochemistry 83(5): 1235-1238.
- Chazot, PL., Lawrence, S. & Thompson, CL. (2002). Studies on the subtype selectivity of CP-101,606: evidence for two classes of NR2B-selective NMDA receptor antagonists. Neuropharmacology 42(3): 319-324.