title: The neural stem cell fate determinant TRIM32 regulates complex behavioral traits.
abstract: In mammals, new neurons are generated throughout the entire lifespan in two restricted areas of the brain, the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ)-olfactory bulb (OB) system. In both regions newborn neurons display unique properties that clearly distinguish them from mature neurons. Enhanced excitability and increased synaptic plasticity enables them to add specific properties to information processing by modulating the existing local circuitry of already established mature neurons. Hippocampal neurogenesis has been suggested to play a role in spatial-navigation learning, spatial memory, and spatial pattern separation. Cumulative evidences implicate that adult-born OB neurons contribute to learning processes and odor memory. We recently demonstrated that the cell fate determinant TRIM32 is upregulated in differentiating neuroblasts of the SVZ-OB system in the adult mouse brain. The absence of TRIM32 leads to increased progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated OB neurons. Here, we present novel data from behavioral studies showing that such an enhancement of OB neurogenesis not necessarily leads to increased olfactory performance but in contrast even results in impaired olfactory capabilities. In addition, we show at the cellular level that TRIM32 protein levels increase during differentiation of neural stem cells (NSCs). At the molecular level, several metabolic intermediates that are connected to glycolysis, glycine, or cysteine metabolism are deregulated in TRIM32 knockout mice brain tissue. These metabolomics pathways are directly or indirectly linked to anxiety or depression like behavior. In summary, our study provides comprehensive data on how the impairment of neurogenesis caused by the loss of the cell fate determinant TRIM32 causes a decrease of olfactory performance as well as a deregulation of metabolomic pathways that are linked to mood disorders.
authors: ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Westfälische Wilhelms-Universität Münster Münster, Germany ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg Luxembourg, Luxembourg.
authors: Anna-Lena
authors: AL
authors: Hillje
authors: Department of Behavioural Biology, Westfälische Wilhelms-Universität Münster Münster, Germany.
authors: Elisabeth
authors: E
authors: Beckmann
authors: ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Westfälische Wilhelms-Universität Münster Münster, Germany ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg Luxembourg, Luxembourg.
authors: Maria A S
authors: MA
authors: Pavlou
authors: Life Sciences Research Unit, University of Luxembourg Luxembourg, Luxembourg.
authors: Christian
authors: C
authors: Jaeger
authors: Life Sciences Research Unit, University of Luxembourg Luxembourg, Luxembourg.
authors: Maria P
authors: MP
authors: Pacheco
authors: Life Sciences Research Unit, University of Luxembourg Luxembourg, Luxembourg.
authors: Thomas
authors: T
authors: Sauter
authors: ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, Westfälische Wilhelms-Universität Münster Münster, Germany ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg Luxembourg, Luxembourg.
authors: Jens C
authors: JC
authors: Schwamborn
authors: Department of Behavioural Biology, Westfälische Wilhelms-Universität Münster Münster, Germany.
authors: Lars
authors: L
authors: Lewejohann
keywords: adult neurogenesis; brain metabolism; cell fate determinant; neural stem cells; olfactory behavior