Molecular Psychiatry

Our group in 2019 (from the left): Dilhan Esen-Şehir, Jessica Manchen, Florian Freudenberg, Anna Yotova, Julia Henninger


Our research group is interested in identifying the molecular mechanisms involved in the development of psychiatric disorders, particularly those with an onset in adolescence and early adulthood (i.e. schizophrenia, affective disorders, and ADHD). Our main focus are the synaptic mechanisms of the glutamatergic synapse with a particular interest on proteins and protein-protein interactions. The main target here is the protein network encompassing AMPA and NMDA receptors, their auxiliary subunits, as well as neuronal nitric oxide synthase (NOS-I) and its adapter protein (NOS1AP) and their interaction partners. In addition, we investigate the effect of environmental factors (e.g. stress, inflammation, drug abuse) on these molecular targets, and how environmental and genetic factors interact to cause psychiatric disorders. By targeting these pathways, genetically and pharmacologically, we aim to identify the aetiology as well as novel treatment opportunities for these disorders.

To investigate these mechanisms, we utilize a wide range of methods, including behavioural and molecular phenotyping of mice, cell culture models, in vitro and in vivo viral gene transfer, morphological and histological analyses, as well as the genetic and molecular investigation of human biosamples. Moreover, in collaboration with Prof. Dr. Michael Plichta, we are investigating the effects of genetic variants on behavioural performance in human subject.

Selection of current projects:

  1. Investigating the interaction of NOS-I and NOS1AP in schizophrenia using a translational approach in mice, human and murine cell cultures and in human subjects.
  2. Analysis of synaptotagmin 1 overexpression and methylphenidate treatment on dendritic morphology
  3. Assessing the role of AMPA receptors and their auxiliary subunits in cognition and depression-like phenotypes using viral gene transfer and analyses in knockout mice

 

Funding Sources:

  • DAAD (short-term grant to Gözde Ayhan in 2020)
  • DFG (Research Grant funding from 2014-2017 & 2017-2019)
  • BMBF (DAAD PPP Finland funding scheme from 2017-2019)
  • Avicenna Studienwerk (PhD scholarship to Dilhan Esen from 2018-2021).
  • JSCNP (Overseas trainees fellowship to Makoto Kinoshita from 2017-2018)
  • Russian Ministry of Education (Russian Presidential scholarship to Nikolai Fattakhov from 2016-2017)

Group members:

  • Florian Freudenberg (PI)
  • Dilhan Esen-Şehir (PhD student, funded by the Avicenna Studienwerk)
  • Susanne Schillo (MD student)
  • Christina Sauerland (BSc student)
  • Gwenn Dequatremare (BSc student)
  • Hannah Wojtzik (BSc student)
  • Gözde Ayhan (Postdoc/guest researcher; funded by the DAAD)

Former members:

  • Esin Candemir (PhD student/Postdoc)
  • Nikolai Fattakhov, Bruna Santos, and Gözde Ayhan (guest PhD students)
  • Nicole Odersky, Saleha Arshad, and Veronika Frerichs (MD students)
  • Makoto Kinoshita (Postdoc/guest researcher)
  • Anna Yotova, Jessica Manchen and Evelien Willemijn Burghgraef (MSc students)
  • Anita Kumar, Solmaz Bikas, Julia Henninger (BSc students)

Collaborations:

Dr. Michael Courtney (Turku Centre for Biotechnology, Finland)

Dr. Will Norton (University of Leicester, United Kingdom)

Prof. Dr. Jakob von Engelhardt (University Medical Center of the Johannes Gutenberg University Mainz, Germany)

 

Selected publications:

  • Freudenberg F. Quantitative analysis of Gria1, Gria2, Dlg1 and Dlg4 expression levels in hippocampus following forced swim stress in mice. In press in Scientific Reports. Scientific reports, 9(1), 14060. https://doi.org/10.1038/s41598-019-50689-w
  • Esen-Sehir D, Bittner R, Courtney MJ, Reif A, Freudenberg F. Establishing an effective dose for chronic intracerebroventricular administration of clozapine in mice. In press in Acta Neuropsychiatrica. Acta neuropsychiatrica, 31(6), 305–315. https://doi.org/10.1017/neu.2019.31
  • Grünewald L, Chiocchetti AG, Weber H, Scholz CJ, Schartner C, Freudenberg F, Reif A. Knockdown of the ADHD Candidate Gene Diras2 in Murine Hippocampal Primary Cells. J Atten Disord. In press. https://doi.org/10.1177/1087054718822129
  • Grünewald L, Becker N, Camphausen A, O’Leary A, Lesch K-P, Freudenberg F, Reif A. Expression of the ADHD candidate gene Diras2 in the brain. Journal of Neural Transmission 125(6):913-923. https://doi.org/10.1007/s00702-018-1867-3
  • Freudenberg F, O’Leary A, Aguiar DC, Slattery DA (2018) Challenges with modelling anxiety disorders: a possible hindrance for drug discovery. Expert Opinion On Drug Discovery 13(4):279-281. https://doi.org/10.1080/17460441.2018.1418321
  • Freudenberg F, Resnik E, Kolleker A, Celikel T, Sprengel R, Seeburg PH (2016) Hippocampal GluA1 expression in Gria1-/- mice only partially restores spatial memory performance deficits. Neurobiology of Learning and Memory 135:83-90. https://doi.org/10.1016/j.nlm.2016.07.005
  • Candemir E, Kollert L, Weißflog L, Geis M, Müller A, Post AM, O'Leary A, Harro J, Reif A, Freudenberg F (2016) Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia-related alterations in dendritic morphology. European Neuropsychopharmacology 26(4):741-755. https://doi.org/10.1016/j.euroneuro.2016.01.008
  • Freudenberg F, Celikel T, Reif A (2015) The role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in depression: Central mediators of pathophysiology and antidepressant activity? Neuroscience & Biobehavioral Reviews 52:193-206. https://doi.org/10.1016/j.neubiorev.2015.03.005
  • Freudenberg F, Alttoa A, Reif A (2015) Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. Genes, Brain and Behavior 14(1):46-63. https://doi.org/10.1111/gbb.12193
  • Freudenberg F, Marx V, Mack V, Layer LE, Klugmann M, Sprengel R, Seeburg PH, Celikel T (2013) GluA1 and its PDZ-interaction: a role in experience-dependent behavioral plasticity in the forced swim test. Neurobiology of Disease 52:160-167. https://doi.org/10.1016/j.nbd.2012.12.003