Neuroscience in Denmark


Back to overview


General information

Name (center, department, group or other)
Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, Copenhagen
Contact name
Bente Pakkenberg
Contact title
Professor, Lab Director
Date
5. May 2017
(Last edited: 8. September 2017)

Brief description of research activities

The laboratory integrates clinical and basic research in joint projects with the Neurological Clinic at Bispebjerg Hospital. The research combines biomarker discovery approaches in blood and cerebrospinal fluid from patient cohorts being followed at the Clinic, with post-mortem stereological and molecular biology studies on brain tissue from these patient groups through access to the Bispebjerg Brain Bank. The diseases of interest include Parkinson’s disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), Amyotrophic Lateral Sclerosis (ALS). One line of research quantifies disease-related neuronal cell loss and glia activation based on stereological estimations of cell population numbers in disease-relevant cortical and subcortical regions of MSA and PD patients relative to age-matched controls. In addition, we perform disease-specific cytokine profiling in the different regions of interest and large genome-wide screening to identify altered pathways related to neuroinflammation. Combined with proteomics approaches we aim at identifying altered protein products related to these pathways. In a clinically well-characterized patient cohort, we characterize differences in alpha-synuclein autoantibody affinity in MSA and PD patients and relate them to disease progression. We further investigate whether there is a genetic component to the shift in immune response differences observed in these patients. In the same patient cohort, we relate the in vivo results with the biomarker properties of the protein candidates identified in the post-mortem study. In parallel, we are in the process of establishing an animal model of MSA in order to perform intervention and proof-of-mechanism studies by help of this preclinical animal model.

Besides, we also conduct preclinical studies within systems neuroscience. Here our interest is in understanding the neural substrates implicated in executive function. Emphasis is in the interaction between serotonin, dopamine and glutamatergic receptors and their role in modulating prefrontal cortex function. By applying neuronal tracing, receptor autoradiography, intracellular pathway analyses, brain mapping of neuronal and pathway activation by c-Fos stereological quantification, gene expression analyses and protein levels measurements in animal models with inbred behavioral phenotypes, our aim is to elucidate how alterations in these receptors may be involved in the cognitive manifestations associated with neuropsychiatric and neurodegenerative diseases. Our focus is mainly on dopamine related disorders, like addiction, schizophrenia and Parkinson.

Keywords

Parkinson, Parkinsonisme, neuroimmunology, neuroanatomy, stereology, brainbank, biobank, schizophrenia, clinical studies, preclinical studies, gene expression profiling analysis

Research tools and techniques

Stereology, qPCR, western blotting, ELISA, histo- and immunotechniques, neuronal tracing, brain mappingof neuronal activation

Scientific Personnel

No of Associate Professors/Postdocs: 6
No of PhD students: 2
Other: 6

Key references from within the last 5 years

Rydbirk R, Elfving B, Andersen MD, Langbøl MA, Folke J, Winge K, Pakkenberg B, Brudek T, Aznar S. Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients. Neurobiol Dis. 2017, 106:269-278.

Brudek T, Winge K, Folke J, Christensen S, Fog K, Pakkenberg B, Pedersen LØ. Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a step towards immunotherapeutic strategies. Mol Neurodegener. 2017, 7;12(1):44.

Nykjaer CH, Brudek T, Salvesen L, Pakkenberg B. Changes in the cell population in brain white matter in multiple system atrophy. Mov Disord. 2017 Apr 10. doi: 10.1002/mds.26979.

Fomsgaard L, Moreno JL, de la Fuente Revenga M, Brudek T, Adamsen D, Rio-Alamos C, Saunders J, Klein AB, Oliveras I, Cañete T, Blazquez G, Tobeña A, Fernandez-Teruel A, Gonzalez-Maeso J, Aznar S. Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains. Mol Neurobiol. 2017 Mar 6. doi: 10.1007/s12035-017-0457-y.

Rydbirk R, Folke J, Winge K, Aznar S, Pakkenberg B, Brudek T. Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases. Sci Rep. 2016 Nov 17;6:37116.

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

Kjær M, Fabricius K, Sigaard RK, Pakkenberg B. Neocortical Development in Brain of Young Children-A Stereological Study. Cereb Cortex. 2016 Oct 12. [Epub ahead of print] PubMed PMID: 27733541.

Aznar S, Hervig Mel-S. The 5-HT2A serotonin receptor in executive function: Implications for neuropsychiatric and neurodegenerative diseases. Neurosci Biobehav Rev. 2016 May;64:63-82. doi: 10.1016/j.neubiorev.2016.02.008.

Brudek T, Winge K, Rasmussen NB, Bahl JM, Tanassi J, Agander TK, Hyde TM, Pakkenberg B. Altered α-synuclein, parkin, and synphilin isoform levels in multiple system atrophy brains. J Neurochem. 2016 Jan;136(1):172-85.

Salvesen L, Winge K, Brudek T, Agander TK, Løkkegaard A, Pakkenberg B. Neocortical Neuronal Loss in Patients with Multiple System Atrophy: A Stereological Study. Cereb Cortex. 2017 Jan 1;27(1):400-410.

Scherfigsvej 7
2100 Copenhagen Ø
Denmark
Tel. +45 39 12 80 00
CVR-nr. 11 81 49 13
info@thebrainprize.org
www.thebrainprize.org
Nils Axelsen Ralf Hemmingsen Lauritz Holm-Nielsen Ralf Hemmingsen Jens Oddershede Jens Frederik Rehfeld Anders Bjørklund