Neurobiology Research Unit

Jens Damsgaard Mikkelsen

Senior Scientist, MD, PhD

Scientific interests| Biography
Publications | Address

Scientific interests

The overall goal of my work is to achieve a better understanding of the mechanism of drug action in experimental models and in humans, and thereby identify new pharmaceuticals for the treatment of psychiatric and neurological disease.

The ongoing research falls into four major areas:

A)     The role of a7 nicotinergic receptors (a7 nAChR) in cognition and in schizophrenia

We have shown that pharmacological activation of the alpha7 nACR leads to neuronal excitation and activation of several immediate early genes in the medial prefrontal cortex and in the ventrolateral orbital cortex. By studying the effect of the same molecules on attention and working memory, we will analyze to what extent the molecular effects and the behavioral effects are related, and whether these drugs are useful for the treatment of cognitive dysfunction in schizophrenia.

B)     Kisspeptins and sexy peptides

We have together with Valerie Simonneaux and her group at the CNRS in Strasbourg, France (http://inci.u-strasbg.fr/dept_a/en/dept_a.html) shown that kisspeptin and RFRP are controlled by the length of the photoperiod. We are interested in the distribution of kisspeptin and RFRP in the mammalian brain and their expression is regulated by melatonin and other signals. We are also highly interested in the effects of these peptides on reproduction and sexuality

C)    The role of Tesofensine in the control of body weight

Tesofensine is a triple monoamine uptake inhibitor producing a strong effect on body weight developed by NeuroSearch. We are interested to study the metabolic effect of Tesofensine in animal models of obesity, and to correlate these effects to clinical studies.

D)    Acute and chronic effects of anxiolytics and antidepressants

We have shown that antidepressants produce plastic changes in the cortex, and that this effect is partly regulated by the activity of the hypothalamo-pituitary adrenal axis. Current studies are done to investigate the role of antidepressants, anxiolytics and stress on gene expression in the brain. Together with Alexander Kiss, Department of Experimental Endocrinology, Bratislava, Slovakia (www.endo.sav.sk/D-morphology.htm)

Biography

2008-	Senior scientist at the Neurobiology Research Unit
2002-2008	Neurosearch, Head, Department of Translational Neurobiology Scientific Director – CNS R&D
2000-2002	Chief Scientific Officer and CEO, Azign Bioscience A/S, acquired by NeuroSearch A/S 2002
1998-2000	Zealand Pharmaceuticals A/S Director, Molecular and Cellular Biology, Diabetes Pharmacology
1995-1998	Lundbeck, Department Head, and Senior Project Manager, Department of Neurobiology,
1993	DMSc from University of Copenhagen, Thesis: The neural basis of circadian rhythms
1986	MD from University of Copenhagen

Publications

The following is a list of selected publications from the past five years.

2005

Abrams JK, Johnson PL, Hay-Schmidt A, Mikkelsen JD, Shekhar A, and Lowry CA (2005) Serotonergic systems underlying actions of anxiogenic drugs. Neuroscience. 133: 983-997

2006

Mikkelsen JD and Woldbye D (2006) Accumulated Increase in Neuropeptide Y and Somatostatin Gene Expression of the Rat in Response to Repeated Electroconvulsive Stimulation. J Psych Research 40(2):153-9.
Revel FG, Saboureau, M, Masson-Pévet, M, Pévet, P, Mikkelsen JD, Simonneaux V (2006) KiSS-1: A likely candidate for the photoperiodic control of Reproduction. Chronobiol. Int. 23:277-287.
Hansen HH, Ebbesen C, Mathiesen C, Weikop P, Rønn LCB, Waroux O, Scuvée-Moreau J, Seutin V and Mikkelsen JD (2006) The KCNQ opener retigabine inhibits mesencephalic dopaminergic neurons of the rat. Journal of Pharmacology and Experimental Therapeutics. 318: 1006-1019.
Kiss A, Søderman A, Bundzikova J, Pirnik Z, and Mikkelsen JD (2006) Zolpidem induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat. Brain Research Bulletin. 71:200-207

2007

Revel FG, Ansel L, Klosen P, Pévet P, Mikkelsen JD, Simonneaux V (2007) Kisspeptin: a key link to seasonal breeding. Rev Endocr Metab Disord. 8:57-65.
Hansen HH, Timmermann DB, Peters D, Walters C, Damaj I, and Mikkelsen JD (2007) Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic regions of the rat forebrain: an effect similar to antipsychotics. J Neurosci Research 85:1810-1818.

2008

Larsen MH, Hay-Schmidt A,. Rønn LCB and Mikkelsen JD (2008) Temporal profile on biomarkers in the hippocampus after treatment with selective and mixed antidepressants. Eur J. Pharmacol. 578:114-122.
Revel FG, Saboureau M, Pévet P, Simonneaux V, Mikkelsen JD (2008) RFamide-related peptide gene is a melatonin-driven photoperiodic gene. Endocrinology, 148: 902-912.
Hansen H, Masotte L, Seutin V, Jentsch TJ, Aznar S and Mikkelsen JD (2008) Kv7 Channels: Interaction with dopaminergic and serotonergic neurotransmission in the CNS. J Neurophysiol. 586:1823-32.
Søderman A, Thomsen MS, Hansen HH, Nielsen EØ, Jensen MS, West MJ, and Mikkelsen JD (2008) The nicotinic alpha7 acetylcholine receptor agonist ssr180711 is unable to activate limbic neurons in mice overexpressing human amyloid-beta(1-42). Brain Research, 1227:240-247

2009

Mikkelsen JD, Simonneaux V (2009) The neuroanatomy of the kisspeptin system in the mammalian brain. Peptides. 30: 26-33
Simonneaux V, Ansel L, Klosen P, Pévet P, Mikkelsen JD (2009) Kisspeptins and seasonal control of reproduction in hamsters. Peptides. 30:146-53.
Mikkelsen JD, Bentsen AH, Ansel L, Simonneaux V, and Juul A (2009) Comparison of the effects of peripherally administered kisspeptins. Regul Pept. 152:95-100
Bendová Z, Sumová A and Mikkelsen JD (2009) Circadian and developmental analysis of NMDA-R1 subunit splice variants and NMDA-R3A and 3B subunits expression in the rat suprachiasmatic nucleus. Neuroscience 159(2):599-609
Revel FG, Mikkelsen JD, Simonneaux V, Masson-Pévet M (2009) Melatonin controls seasonal breeding through a network of hypothalamic targets. Neuroendocrinology, 90(1):1-14
Thomsen MS, Christensen DZ, Hansen HH, Redrobe JP, Mikkelsen JD (2009) Alpha 7 nicotinic acetylcholine receptor activation prevents schizophrenia-relevant behavioral and molecular changes induced by repeated PCP treatment. Neuropharmacology; 56:1001-9.
Bundzikova J, Pirnik Z, Zelena D, Mikkelsen JD, Kiss A. Alpha2-adrenergic impact on hypothalamic magnocellular oxytocinergic neurons in long evans and brattleboro rats: effects of agonist and antagonists. Cell Mol Neurobiol 2009;29:1015-23

2010

Thomsen, MS, Hansen HH, Timmerman, DB, Mikkelsen, JD (2010) Cognitive improvement by activation of α7 nicotinic acetylcholine receptors: From animal models to human pathophysiology, Current Pharmaceutical Design,16:323-43.

In press

Mikkelsen JD, Thomsen MS, Hansen HH and Lichota J (2010) Use of biomarkers in discovery of novel anti-schizophrenia drugs. Drug Discovery Today. 15(3-4):137-141.
Thomsen MS, Hansen HH, and Mikkelsen JD (2010) Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions. Neurochem Int, In press
Bentsen AH, Ansel L, Simonneaux V, Tena-Sempere M, Juul A, and Mikkelsen JD (2010) Gradually maturation of the kisspeptinergic neurons in the arcuate nucleus coincide with puberty. Peptides. 31(2):275-83
Thomsen MS, Hay-Schmidt A, Hansen HH and Mikkelsen JD (2010) Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain. Cerebral Cortex, In press
Hansen HH, Hansen G, Tang-Christensen M, Larsen PJ, Axel AMD, Raben A, Mikkelsen JD (2010) Tesofensine, a novel triple monoamine reuptake inhibitor produces a sustained weight loss and improve glycaemic control in the diet-induced obese rat. Eur J Pharmacol. In press.
Axel AMD, Mikkelsen JD, Hansen HH (2010) Tesofensine, a novel triple monoamine reuptake inhibitor induces hypophagia by combined stimulation of norepinephrinic and dopaminergic pathways in diet-induced obese rats. Neuropsychopharmacology. In press.
Castellano JM, Bentsen AH, Romero M, Pineda R, Ruiz-Pino F, Garcia-Galiano D, Sánchez-Garrido MA, Pinilla L, Mikkelsen JD and Tena-Sempere M (2010) Hypogonadotropic hypogonadism during acute inflammation is associated to reduced level of kisspeptin and responsiveness, independent of the anorectic effects of the inflammatory challenge. Am J Physiol. In press

Address

Neurobiology Research Unit
Rigshospitalet
Blegdamsvej 9
DK-2100 Copenhagen, Denmark
Phone: +45 3545 6718
Fax: +45 3545 6713
E-mail: jens.mikkelsen#nru.dk