Forschungsschwerpunkte Frau Prof. Dr. rer. nat. Claudia Grothe
Physiology and therapy of peripheral nerve regeneration (siehe Projekte Prof. Haastert-Talini)
Involvement of Fibroblast Growth Factor-2 in alcohol use disorder
DFG-funded project in cooperation with Prof. Segev Barak, PhD, Tel Aviv University, School of Psychological Sciences The Sagol School of Neuroscience
Characteristic hallmarks of alcohol addiction, such as psychological and physical dependence and withdrawal syndrome, typically appear only after prolonged excessive drinking. Therefore, it is believed that alcohol addiction results from neuroadaptations in the brain, which are induced by the chronic excessive alcohol consumption. Some of these neuroadaptations are thought to promote the transition from controlled, moderate alcohol intake to out-of-control drinking, whereas others are thought to protect against alcohol use disorder (AUD) phenotypes. Alterations in the expression of growth factors have been implicated in AUD, and is attributed to their capacity to regulate dopaminergic function in the dopamine (DA) mesolimbic pathway. For GDNF and BDNF it is suggested that these factors attenuate alcohol-drinking behavior.
FGF-2 and FGFR1 are highly expressed in the mesolimbic and nigrostriatal circuitries, as well as in the hippocampus and frontal cortex. Recent studies in my group revealed that loss of FGF-2 causes a developmental hyperplasia of the SNc, leading to inadequate basal ganglia control and increased volume of striatum, which results in increased DAergic transmission. DAergic transmission has been implicated in several neuropsychiatric disorders, including addiction, and indeed a growing body of evidence from animal and human genetic studies indicates that FGF-2 is involved in neuropsychiatric disorders, such as depression, anxiety, and schizophrenia. Preliminary results from our cooperation partner (Segev Barak, School of Psychological Sciences and Sagol school of Neuroscience, Tel Aviv University) suggest that alcohol induces neuroadaptations in the FGF-2 system, and that FGF-2 enhances alcohol consumption.
The general objective of this cooperative project (with Segev Barak) is to elucidate the mechanisms, by which FGF-2 acts to control alcohol-drinking behaviors. Specific aims are: 1. Identify the FGF-2 isoforms implicated in the bidirectional effects of FGF-2 and alcohol-drinking behaviors in the brain. 2. Elucidate the role of the mesencephalic dopaminergic system in the interaction between alcohol and FGF-2. 3. Determine whether FGF-2 mediates the effects of alcohol on other growth factor systems.
Investigation of the regenerative potential of compounds identified in a high-throughput screening in in vitro and in vivo models of Parkinson’s disease
REBIRTH - funded, “Innovation/Synergy grants”
Collaboration project: Prof. Dr. med. Günter U. Höglinger, Neurology, MHH; Prof. Dr. rer. nat. Claudia Grothe, Neuranatomy and Cell Biology, MHH; Co-PI: Dr. med. Matthias Höllerhage, Neurology, MHH
There is no therapy available that prevents the neurodegenerative process in neurodegenerative disorders such as Parkinson’s disease. The induction of regenerative intracellular processes before cell death could help to restore neuronal damage and thereby reverse part of the neurodegenerative process. In this project compounds that were shown to be protective against neuronal cell death will be investigated, if they have the potential to also restore neuronal damage.