Forschung

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.

Watch this Instagram Reel from the Goethe University Career Service showing the average day in the life of our very own Melike Aydin (BSc student in 2023)

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

• Florian Freudenberg (PI)
• Dilhan Esen (PhD student, funded by the Avicenna Studienwerk)
• Susanne Schillo
• Aayush Marishi (MSc student, PBioC)
• Johanna Diehl (MSc student, INS)
• Lea Schöls (MD student)
• Yongwei Xia (MD student)
• Lina Schäfer (MD student)
• Freya Schroedter (BSc student)
• Melike Aydin (BSc student)
• Anna Paula Amorim Marques (visiting researcher, University of São Paulo)

• Esin Candemir (PhD student/Postdoc)
• Nikolai Fattakhov, Bruna Santos, and Gözde Ayhan (guest PhD students)
• Makoto Kinoshita (Postdoc/guest researcher)
• MD students: Nicole Schenk, Saleha Arshad, and Veronika Frerichs
• MSc students: Anna Yotova, Jessica Manchen, Evelien Willemijn Burghgraef, Gloria Mico, Tsendmaa Tsengenbayar
• BSc students: Anita Kumar, Solmaz Bikas, Julia Henninger, Christina Sauerland, Gwenn Dequatremare, Hannah Wojtzik, Johanna Diehl, Soner Cagun, Leah Luwisch, Melosha Puspathasan, Christian Rische, Harishny Sarma

• Main-Campus Stipendiatenwerk (Stiftung Polytechnische Gesellschaft (stipend to Florian Freudenberg from 2021-2022)
• 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 2018-2022).
• JSCNP (Overseas trainees fellowship to Makoto Kinoshita from 2017-2018)
• Russian Ministry of Education (Russian Presidential scholarship to Nikolai Fattakhov from 2016-2017)

For a complete list of publications see Google scholar.

• Candemir, E., Fattakhov, N., Leary, A. O., Slattery, D. A., Courtney, M. J., Reif, A., & Freudenberg, F. (2023). Disrupting the nNOS/NOS1AP interaction in the medial prefrontal cortex impairs social recognition and spatial working memory in mice. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 67, 66–79. https://doi.org/10.1016/j.euroneuro.2022.11.006

• Freudenberg, F., Althen, H., Falk, K., Bittner, R. A., Reif, A., & Plichta, M. M. (2022). Test-retest reliability of prepulse inhibition (PPI) and PPI correlation with working memory. Acta neuropsychiatrica, 34(6), 344–353. https://doi.org/10.1017/neu.2022.19

• O'Leary, A., Fernàndez-Castillo, N., Gan, G., Yang, Y., Yotova, A. Y., Kranz, T. M., Grünewald, L., Freudenberg, F., Antón-Galindo, E., Cabana-Domínguez, J., Harneit, A., Schweiger, J. I., Schwarz, K., Ma, R., Chen, J., Schwarz, E., Rietschel, M., Tost, H., Meyer-Lindenberg, A., Pané-Farré, C. A., … Reif, A. (2022). Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits. Molecular psychiatry, 27(11), 4464–4473. https://doi.org/10.1038/s41380-022-01722-4

• Esen-Sehir, D., Kopf, J., Hägele, S., Plichta, M. M., Reif, A., & Freudenberg, F. (2022). Influence of NOS1AP Risk Variants on the Corrected QT (QTc) Interval in the Pharmacotherapy of Schizophrenia. Pharmacopsychiatry, 10.1055/a-1811-7241. Advance online publication. https://doi.org/10.1055/a-1811-7241

• Freudenberg, F., Candemir, E., Chen, X., Li, L. L., Esen-Sehir, D., Schenk, N., Kinoshita, M., Grünewald, L., Frerichs, V., Fattakhov, N., Manchen, J., Bikas, S., Kumar, A., OLeary, A., Slattery, D. A., von Engelhardt, J., Courtney, M. J., & Reif, A. (2021). Hippocampal overexpression of NOS1AP promotes endophenotypes related to mental disorders. EBioMedicine, 71, 103565. https://doi.org/10.1016/j.ebiom.2021.103565

• Esen-Sehir, D., Courtney, M. J., Bittner, R. A., Reif, A., & Freudenberg, F. (2019). Establishing an effective dose for chronic intracerebroventricular administration of clozapine in mice. Acta neuropsychiatrica, 31(6), 305–315. https://doi.org/10.1017/neu.2019.31

• Grünewald, L., Chiocchetti, A. G., Weber, H., Scholz, C. J., Schartner, C., Freudenberg, F., & Reif, A. (2021). Knockdown of the ADHD Candidate Gene Diras2 in Murine Hippocampal Primary Cells. Journal of attention disorders, 25(4), 572–583. https://doi.org/10.1177/1087054718822129

• Candemir, E., Kollert, L., Weißflog, L., Geis, M., Müller, A., Post, A. M., 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 : the journal of the European College of 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 and 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