My primary research interests comprise psychiatric- and neurodegenerative disorders.
Depression and antidepressant treatment
Depression is a highly debilitating disorder which affects millions of people worldwide. Studies of patients with major depression show structural alterations of the hippocampus that are opposed by treatment using antidepressants and electroconvulsive therapy (ECT). Because ECT and antidepressant therapy has been shown to stimulate cell division, and increase the volume of the hippocampus, it is believed that the formation of new neurons (neurogenesis) may be an important component for improvements of depressive episodes. Using stereological methods I have studied structural changes of the hippocampus in depressive-like rats as well as quantified the number of newly-formed neurons, and their survival following repeated electroconvulsive stimulation (ECS). Published in Hippocampus (2015), 25(1):72-80
Multiple System Atrophy (MSA)
MSA is a fatal neurodegenerative disorder of unknown etiology. In the early progression it resembles Parkinson's disease, but the symptoms are much broader and involve a combination of parkinsonism as well as autonomous and cerebellar symptoms. MSA pathology is demonstrated on the basis of inclusion bodies in specific glial cells (oligodendrocytes). These inclusions mainly consist of insoluble protein, α-synuclein, which, via a yet unknown mechanism, leads to the loss of nerve cells in brain regions that are vital for the control of movement, coordination and balance.
Transgenic MSA mouse model: We are currently generating MSA mouse models for future studies of the pathological mechanisms that may be involved in initiating the neurodegenerative cascade in MSA. Using behavioral testing the motor function of the mice is assessed at selected time intervals. In relevant regions of the MSA mouse brains α-synuclein gene- and protein expression will be analyzed together with thorough neuropathological evaluations. Furthermore, we will perform stereological quantifications of neurons and glial cells to investigate whether we can reproduce human MSA brain pathology.
Neuronal quantification of post-mortem cerebellum: Besides coordinating muscle activity, the cerebellum is central to the maintenance of balance and spatial orientation. Based on the knowledge of cell morphology and function in the healthy brains, I am currently using stereology to examine whether there are changes in the number and volume of specific nerve cells in the cerebellum in patients with MSA.
Olesen MV, Needham EK, Pakkenberg B. The Optical Fractionator Technique to Estimate Cell Numbers in a Rat Model of Electroconvulsive Therapy. J Vis Exp. 2017 Jul 9;(125).
Hervig ME, Jensen NCH, Rasmussen NB, Rydbirk R, Olesen MV, Hay-Schmidt A,
Pakkenberg B, Aznar S. Involvement of serotonin 2A receptor activation in
modulating medial prefrontal cortex and amygdala neuronal activation during
novelty-exposure. Behav Brain Res. 2017 May 30;326:1-12.
Olesen MV, Wörtwein G, Folke J, Pakkenberg B. Electroconvulsive stimulation
results in long-term survival of newly generated hippocampal neurons in rats.
Hippocampus. 2017 Jan;27(1):52-60.
Rasmussen NB, Olesen MV, Brudek T, Plenge P, Klein AB, Westin JE, Fog K,
Wörtwein G, Aznar S. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's
Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study.
Parkinsons Dis. 2016;2016:3682936.
Olesen MV, Christiansen SH, Gøtzsche CR, Nikitidou L, Kokaia M, Woldbye DP (2012) Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with anxiolytic-like and proconvulsive effects in mice. Journal of Neuroscience Research 90 (2): 498-507.
Olesen MV, Christiansen SH, Gøtzsche CR, Holst B, Kokaia M, Woldbye DP (2012) Moderate hyperactivity induced by rAAV vector-mediated Y5 neuropeptide Y receptor overexpression in mice. Neuropeptides 46 (2): 71-79.
Gøtzsche CR, Sørensen AT, Nikitidou L, Olesen MV, Sørensen G, Christiansen SH, Ängehagen M, Woldbye DP (2012) Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures. Neurobiology of Disease 45 (1): 288-96.
Christiansen SH, Olesen MV, Wörtwein G, Woldbye DP (2011) Fluoxetine reverts chronic stress- induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice. Behavioural Brain Research 216(2): 585-91.
Woldbye DP, Ängehagen M, Gøtzsche CR, Kristiansen H, Sørensen AT, Christiansen SH, Olesen MV, Nikitidou L, Hansen TVO, Kanter-Schlifke I, Kokaia M (2010) AAV vector- induced overexpression of neuropeptide Y Y2 receptor in the hippocampus supresses seizures. Brain 133 (9): 2778-2788.
Thomsen M, Wörtwein G, Olesen MV, Begstrup M, Havez S, Bolwig TG, Woldbye DP (2007) Involvement of Y5 receptor in neuropeptide Y agonist-induced analgesic-like effect in the rat hot plate test. Brain Research 1155: 49-55.
Christensen DZ, Olesen MV, Kristiansen H, Mikkelsen JD, Woldbye DP (2006) Unaltered Neuropeptide Y (NPY)-Stimulated [35S] - GTPγS Binding After Repeated Electrocunvulsive Seizures in Mice. Journal of Neuroscience Research 84: 1282-1291.
Larsen MH, Olesen M, Woldbye DP, Hay-Schmidt A, Hansen HH, Rønn LCB, Mikkelsen JD (2005) Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat.
Brain Research 1064: 161-165.