Universität Regensburg

Peter J. Flor

Anschrift:

Leistungsprofil:

• Research in our laboratory is focused on trying to better understand the complex interactions, at a molecular and cellular level, between stress and genetics that lead to the manifestation of multiple pathologies such as anxiety, reactive depression, neuronal loss, substance abuse and cognitive dysfunction in certain susceptible individuals. This effort is paralleled with investigations towards discovery and characterization of new pharmacological therapies – eventually aiming to counteract the deleterious consequences of acute and chronic stress
• The Flor laboratory works mainly on the role of Metabotropic Glutamate Receptors (mGluRs, the G protein-coupled receptors for the mammalian main excitatory neurotransmitter L-glutamate) in conditions related to Chronic Stress, such as Anxiety, Depression and Substance Abuse.

• mGluR2/3, mGluR5 and mGluR7 are crucially involved in the regulation of physiological processes involved in acute stress and fear/anxiety-related behaviours. However the underlying neurobiochemical, molecular, and cellular pathways are insufficiently understood. Our future research is intended to shed light on these topics!
• Although mGluR2/3, mGluR5 and mGluR7 are emerging as fine-tuning regulators of neuroendocrine function and roles in acute stress are established, there is virtually nothing known about their involvement in chronic stress. We intend to determine the effect of modulation of mGluR2/3, mGluR5 and mGluR7 on physiological and behavioural consequences of chronic psychosocial stress in mammals!
• Over the past two decades we have discovered novel drugs acting on mGluRs, such as PPG, CPCCOEt, MPEP, AMN082, and PHCCC (see publication references below). Over the next years, we intend to increase our knowledge about the exact molecular mechanisms and sites of action of these and related mGluR drugs!

• - Molecular cloning techniques - In vitro pharmacology with cloned, molecularly recombined, and native receptors - Recombinant and native/primary cell culture - Quantitative real-time PCR
• - RNAi – viral and non-viral transfer of shRNA and/or siRNA to cells, tissue, and rodent animals - Transgenic mice, including gene knock-out animals - In vivo rodent Behavioural Pharmacoloy - Molecular Imaging

Publikationen:

• Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease. Greco B, Lopez S, van der Putten H, Flor PJ, Amalric M. J Pharmacol Exp Ther. 2010 Mar;332(3):1064-71.
• mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity. Fendt M, Schmid S, Thakker DR, Jacobson LH, Yamamoto R, Mitsukawa K, Maier R, Natt F, Hüsken D, Kelly PH, McAllister KH, Hoyer D, van der Putten H, Cryan JF, Flor PJ. Mol Psychiatry. 2008 Oct;13(10):970-9.
• Metabotropic glutamate receptor subtype 7 ablation causes dysregulation of the HPA axis and increases hippocampal BDNF protein levels: implications for stress-related psychiatric disorders. Mitsukawa K, Mombereau C, Lötscher E, Uzunov DP, van der Putten H, Flor PJ, Cryan JF. Neuropsychopharmacology. 2006 Jun;31(6):1112-22.
• A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Mitsukawa K, Yamamoto R, Ofner S, Nozulak J, Pescott O, Lukic S, Stoehr N, Mombereau C, Kuhn R, McAllister KH, van der Putten H, Cryan JF, Flor PJ. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18712-7.
• (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Maj M, Bruno V, Dragic Z, Yamamoto R, Battaglia G, Inderbitzin W, Stoehr N, Stein T, Gasparini F, Vranesic I, Kuhn R, Nicoletti F, Flor PJ. Neuropharmacology. 2003 Dec;45(7):895-906.
• Antidepressant and anxiolytic-like effects in mice lacking the group III metabotropic glutamate receptor mGluR7. Cryan JF, Kelly PH, Neijt HC, Sansig G, Flor PJ, van Der Putten H. Eur J Neurosci. 2003 Jun;17(11):2409-17.
• Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective. Bruno V, Ksiazek I, Battaglia G, Lukic S, Leonhardt T, Sauer D, Gasparini F, Kuhn R, Nicoletti F, Flor PJ. Neuropharmacology. 2000 Sep;39(12):2223-30.
• Selective activation of mGlu4 metabotropic glutamate receptors is protective against excitotoxic neuronal death. Bruno V, Battaglia G, Ksiazek I, van der Putten H, Catania MV, Giuffrida R, Lukic S, Leonhardt T, Inderbitzin W, Gasparini F, Kuhn R, Hampson DR, Nicoletti F, Flor PJ. J Neurosci. 2000 Sep 1;20(17):6413-20.
• (R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo. Gasparini F, Bruno V, Battaglia G, Lukic S, Leonhardt T, Inderbitzin W, Laurie D, Sommer B, Varney MA, Hess SD, Johnson EC, Kuhn R, Urwyler S, Sauer D, Portet C, Schmutz M, Nicoletti F, Flor PJ. J Pharmacol Exp Ther. 1999 Jun;289(3):1678-87.

Kooperationsangebot für die Wirtschaft / Praxis:

• Neuropharmacology and drug target validation for psychiatric and neurological disorders
• Drug screening for psychiatric and neurological disorders
• In vivo models for for psychiatric and neurological disorders

Bestehende Kooperationen:

Sonstiges: