My research comprises two parallel lines:
On one side, I am interested in understanding the serotonergic system's involvement in modulating the neural substrates implicated in executive function. Emphasis is on the serotonin 2A receptor's role in prefrontal cortex function through interaction with other receptor and neurotransmitter systems. 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, our aim is to elucidate how alterations in this receptor 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.
On the other side, we conduct studies on human samples from our Brain Bank, in order to find and validate disease-specific biological markers that may be potential candidates as biomarkers for Parkinson and other parkinsonism. Our aim is to provide clinicians with a disease-specific biomarker panel valid for use in the clinics. We believe that access to such a panel would be a strong tool for use in clinical trials, as well as provide clinicians with a much needed instrument for early differential diagnosis between Parkinson Disease from Multiple System Atrophy and other Parkinsonism. Our studies comprise biochemical, genetic, epigenomic and proteomic approaches with focus on neuroinflammatory and neurotrophic related processes.
Publications 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 Oct;106:269-278.
Merchán A, Navarro SV, Klein AB, Aznar S, Campa L, Suñol C, Moreno M, Flores
P. Tryptophan depletion affects compulsive behaviour in rats: strain dependent
effects and associated neuromechanisms. Psychopharmacology (Berl). 2017
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.
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.
Oliveras I, Sánchez-González A, Sampedro-Viana D, Piludu MA, Río-Alamos C,
Giorgi O, Corda MG, Aznar S, González-Maeso J, Gerbolés C, Blázquez G, Cañete T,
Tobeña A, Fernández-Teruel A. Differential effects of antipsychotic and
propsychotic drugs on prepulse inhibition and locomotor activity in Roman high-
(RHA) and low-avoidance (RLA) rats. Psychopharmacology (Berl). 2017
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.
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.
Aznar S and Hervig MES. 2015. The 5-HT2A serotonin receptor in executive function: implications for neuropsychiatric and neurodegenerative diseases. Neuroscience and Biobehavioral Reviews 64 p. 63-82 (2016).
Klein AB, Ultved L, Adamsen D, Santini MA, Tobeña A, Fernandez-Teruel A, Flores P, Moreno M, Knudsen GM, Aznar S, Mikkelsen JD. 2014. 5-HT2A and mGluR2 receptor binding levels are related to differences in impulsive behaviour in the Roman Low- (RLA) and High (RHA) avoidance rat strains. Neuroscience 263:36-45.
Santini MA, Ratner C, Aznar , S, Klein AB, Knudsen GM, Mikkelsen JD. 2013. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia. J.Neurosci.Res. 91(5):634-41.
Aznar S and Klein AB. Regulating prefrontal cortex activation: An emerging role for the 5-HT2A serotonin receptor in the modulation of emotion-based actions? Mol.Neurobiol. 48:841-853. Review.
Clemmensen C, Aznar S, Knudsen GM and Klein AB. 2012. The Microtubule-Associated Protein 1A (MAP1A) is an early molecular target of soluble Ab-peptide. Cell Mol Neurobiol. 32(4): 561-6.
Ruiz-Muñoz AM, Nieto-Escamez FA, Aznar S, Colomina MT, Sanchez-Santed F. 2011.Cognitive and histological disturbances after chlorpyrifos exposure and chronic Aβ(1-42) infusions in Wistar rats. Neurotoxicology 32(6):836-44.
Santini MA, Klein AB, El-Sayed M, Ratner C, Knudsen GM, Mikkelsen JD, Aznar S. 2011.Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation. Neuroscience. Sep 8;190:251-7.
Licht C.L., Kirkegaard L., Zueger M., Gass P., Aznar S., Knudsen, G.M. 2010. The 5-HT4 receptor and 5-HTT binding are altered in two murine depression models. Neurochem.Int. 56(4):603-10.
Aznar S., Klein A.B., Santini M.A.,Knudsen G.M., Henn F., Gass P., Vollmayr B. 2010. Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness. Synapse 64(7):561-565.
Holm P., Ettrup, A., Klein A.B., Santini M.A., El-Sayed M., Elvang, A.B., Stensbøl, T.B., Mikkelsen J.D., Knudsen, G.M., Aznar S. 2010. Plaque deposition dependent decrease in 5-HT2A serotonin receptor in APPswe/PS1dE9 amyloid overexpressing mice. Journal of Alzheimer's Disease 20(4): 1201-13.
Klein AB, Santini MA, Aznar S, Knudsen GM and Rios M. 2010. Changes in 5-HT2A-mediated behaviour and 5-HT2A- and 5-HT1A receptor binding and expression in conditional BDNF knock-out mice. Neuroscience 169(3): 1007-1016.
Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S. 2010. Blood BDNF concentrations reflect brain tissue BDNF levels across species. Int.Journal of Neurospsychopharmacology July 7:1-7 (Epub ahead of print); 2011 Apr;14(3):347-53.
Klein AB, Trajkovska V, Erritzoe D, Haugbol S, Madsen J, Baaré W, Aznar S, Knudsen GM. 2010. Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels. Journal of Cerebral Blood Flow 30(11):e1-7.
Aznar S and Knudsen G.M. 2011. Depression and Alzheimer's Disease: Is Stress the Initiating Factor in a Common Neuropathological Cascade? Journal of Alzheimer Disease 23(2):177-93. Review.
Ziebell M., Khalid U., Klein A.B., Aznar S., Thomsen G., Jensen P. and Knudsen G.M. 2012. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration. Neurobiol.Aging. 33(2): 428. Epub 2010 Dec 22.