Neuroscience in Denmark


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General information

Name (center, department, group or other)
Neurobiology of Cognition Group, Thomsen lab, Section for Experimental Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen
Contact name
Morten Skøtt Thomsen
Contact email
morten#dot#s#dot#thomsen#at#sund#dot#ku#dot#dk
Contact title
Associate Professor, Research Group Leader
Date
25. January 2016


Brief description of research activities

Our research is focused on performing translational studies of neurobiology and neuropharmacology. Our studies have focused on the cholinergic system in the brain, and how it influences behaviour as well as the underlying neural substrates for these behaviours.
The research is pharmacology-oriented and aspires to aid development of drugs to ameliorate cognitive disturbances in disorders such as Alzheimer’s disease and schizophrenia.
A major focus in the lab is to elucidate the functions of the nicotinic acetylcholine receptors in the brain and their involvement in memory and attention. This includes studying how the exxpression and function of these receptors is affected by interactions with other proteins, e.g. a class of proteins called Lynx proteins, as well as NMDA receptors.


Keywords

Translational neuropharmacology
Nicotinic Acetylcholine Receptors
Cognition
Alzheimer's Disease
Human brain tissue
Lynx proteins
Protein-protein interactions
NMDA receptors

Research tools and techniques

Affinity purification using fresh human brain samples
Transgenic mouse models
Functional neuroanatomy
In vivo and in vitro pharmacology
Cell-based assays including transfections and molecular biology

Scientific Personnel

No of Associate Professors/Postdocs: 1
No of PhD students: 3
Other: 4

Key references from within the last 5 years

Thomsen MS, Andreasen JT, Arvaniti M, Kohlmeier KA (2016) Nicotinic acetylcholine receptors in the pathophysiology of Alzheimer’s disease: The role of protein-protein interactions in current and future treatment. Curr Pharm Des, in press. Corresponding author

Thomsen MS, Zwart R, Ursu D, Jensen MM, Pinborg LH, Gilmour G, Wu J, Sher E, Mikkelsen JD (2015) α7 and β2 Nicotinic Acetylcholine Receptor Subunits Form Heteromeric Receptor Complexes that Are Expressed in the Human Cortex and Display Distinct Pharmacological Properties. PLoS One, 10(6):e0130572.

Jensen MM, Arvaniti M, Mikkelsen JD, Michalski D, Pinborg LH, Härtig W, Thomsen MS (2015) Prostate stem cell antigen interacts with nicotinic acetylcholine receptors and is affected in Alzheimer's disease. Neurobiol Aging, 36(4):1629-38. Corresponding author. Here we use affinity purification to show for the first time that PSCA is present and binds to nicotinic receptors in the human brain.

Thomsen MS, Cinar B, Jensen MM, Lyukmanova EN, Shulepko MA, Tsetlin V, Klein AB, Mikkelsen JD (2014) Expression of the Ly-6 family proteins Lynx1 and Ly6H in the rat brain is compartmentalized, cell-type specific, and developmentally regulated. Brain Struct Funct, 219(6):1923-1934. Corresponding author. This provided a characterization of the distribution of Lynx proteins at the subcellular level in the brain

Brooks JM, Pershing ML, Thomsen MS, Mikkelsen JD, Sarter M, Bruno JP (2012) Transient inactivation of the neonatal ventral hippocampus impairs attentional set shifting behavior: reversal with an α7 nicotinic agonist. Neuropsychopharmacology, 37(11):2476-86.

Thomsen MS and Mikkelsen JD (2012) The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia. J Neuroimmunol, 251(1-2):65-72. Corresponding author. Our results went against the knowledge at the time that suggested that activation of the α7 nAChR was needed for anti-inflammatory effects.

Thomsen MS and Mikkelsen JD (2012) Type I and II positive allosteric modulators (PAMs) differentially modulate agonist-induced upregulation of α7 nicotinic acetylcholine receptors (nAChRs). J Neurochem, 123(1):73-83. Corresponding author. This was the first evidence of an in vivo difference between the effects of type I and II allosteric modulators.

Thomsen MS, Weyn A, Mikkelsen, JD (2011). Hippocampal α7 nicotinic acetylcholine receptor levels in patients with schizophrenia, bipolar disorder, or major depressive disorder. Bipolar Disorders, 13(7-8):701-7. Corresponding author. The main goal here was to reproduce a very highly cited but never reproduced result from 1995 that α7 nAChR levels are decreased in schizophrenia – we found no difference.

Thomsen MS, El-Sayed, Mikkelsen, JD (2011). Differential Immediate and Sustained Memory Enhancing Effects of Alpha7 Nicotinic Receptor Agonists and Allosteric Modulators in Rats, PLoS ONE, 6(11):e27014. Corresponding author. This demonstrated that administration of α7 nAChR ligands have pro-cognitive effects that outlast the presence of the compounds in the body.

Thomsen MS, Hay-Schmidt A, Hansen HH, Mikkelsen JD (2010) Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain. Cereb Cortex, 20:2092-102. Corresponding author. This demonstrated the existence of two non-overlapping pathways in the brain regulated by the α7 nAChR.
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