Genetic factors linking metabolic state, behaviour and adult neurogenesis (DFG-GA CR)

• Applicant: Professor Dr. Gerd Kempermann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 162803327

The present research proposal is concerned with the common genetic regulatory network underlying adult hippocampal neurogenesis, spatial learning and susceptibility to metabolic syndrome. Failing adult hippocampal neurogenesis is now being linked to several human neuropsychiatric disorders, such as dementia, depression or anxiety. Epidemiologic data indicates that these conditions are often associated with the development of metabolic syndrome, suggesting a potential pathogenic connection. Our group previously showed that i) adult neurogenesis is differentially regulated in spontaneously hypertensive rat (SHR), an animal model of human metabolic syndrome and attention deficit/hyperactivity disorder, compared to its genetic control; and ii) adult neurogenesis is necessary for cognitive flexibility while learning a hippocampus-dependent spatial task. Here we propose to investigate, using a systems genetics approach, whether the cognitive impairments and metabolic syndrome share underlying molecular mechanisms that impinge on cellular brain plasticity. Specifically, we aim to identify quantitative trait loci (QTLs) linked to adult neurogenesis in the HXB/BXH rat recombinant inbred strains derived from SHR, which are extensively phenotyped for multiple metabolic parameters and hence can be used for defining genetic covariates between metabolic and neurogenesis phenotypes. In parallel, in a collaborative effort, we plan to evaluate behavioural correlates of hippocampusdependent spatial learning and anxiety.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Participating Person: Dr. Ales Stuchlik