TY  - JOUR
A1  - Schäbler, Stefan
A1  - Amatobi, Kelechi M.
A1  - Horn, Melanie
A1  - Rieger, Dirk
A1  - Helfrich‑Förster, Charlotte
A1  - Mueller, Martin J.
A1  - Wegener, Christian
A1  - Fekete, Agnes
T1  - Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation
JF  - Cellular and Molecular Life Sciences
N2  - The fruit fly Drosophila is a prime model in circadian research, but still little is known about its circadian regulation of metabolism. Daily rhythmicity in levels of several metabolites has been found, but knowledge about hydrophobic metabolites is limited. We here compared metabolite levels including lipids between period\(^{01}\) (per\(^{01}\)) clock mutants and Canton-S wildtype  (WT\(_{CS}\)) flies in an isogenic and non-isogenic background using LC–MS. In the non-isogenic background, metabo-lites with differing levels comprised essential amino acids, kynurenines, pterinates, glycero(phospho)lipids, and fatty acid esters. Notably, detectable diacylglycerols (DAG) and acylcarnitines (AC), involved in lipid metabolism, showed lower levels in per\(^{01}\) mutants. Most of these differences disappeared in the isogenic background, yet the level differences for AC as well as DAG were consistent for fly bodies. AC levels were dependent on the time of day in WTCS in phase with food consumption under LD conditions, while DAGs showed weak daily oscillations. Two short-chain ACs continued to cycle even in constant darkness. per\(^{01}\) mutants in LD showed no or very weak diel AC oscillations out of phase with feeding activity. The low levels of DAGs and ACs in per\(^{01}\) did not correlate with lower total food consumption, body mass or weight. Clock mutant flies showed higher sensitivity to starvation independent of their background-dependent activity level. Our results suggest that neither feeding, energy storage nor mobilisation is significantly affected in per\(^{01}\) mutants, but point towards impaired mitochondrial activity, supported by upregulation of the mitochondrial stress marker 4EBP in the clock mutants
KW  - circadian rhythms
KW  - metabolomics
KW  - mitochondrial activity
KW  - tryptophan
KW  - acylcarnitine
KW  - feeding
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232432
SN  - 1420-682X
VL  - 77
ER  - 
TY  - JOUR
A1  - Weissenseel, Sebastian
A1  - Gottscholl, Andreas
A1  - Bönnighausen, Rebecca
A1  - Dyakonov, Vladimir
A1  - Sperlich, Andreas
T1  - Long-lived spin-polarized intermolecular exciplex states in thermally activated delayed fluorescence-based organic light-emitting diodes
JF  - Science Advances
N2  - Spin-spin interactions in organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) are pivotal because radiative recombination is largely determined by triplet-to-singlet conversion, also called reverse intersystem crossing (RISC). To explore the underlying process, we apply a spin-resonance spectral hole-burning technique to probe electroluminescence. We find that the triplet exciplex states in OLEDs are highly spin-polarized and show that these states can be decoupled from the heterogeneous nuclear environment as a source of spin dephasing and can even be coherently manipulated on a spin-spin relaxation time scale T-2* of 30 ns. Crucially, we obtain the characteristic triplet exciplex spin-lattice relaxation time T-1 in the range of 50 mu s, which far exceeds the RISC time. We conclude that slow spin relaxation rather than RISC is an efficiency-limiting step for intermolecular donor:acceptor systems. Finding TADF emitters with faster spin relaxation will benefit this type of TADF OLEDs.
KW  - detected magnetic-resonance
KW  - population oscillations
KW  - polaron delocalization
KW  - charge separation
KW  - hole
KW  - phosphorescence
KW  - singlet
KW  - absorption
KW  - tryptophan
KW  - emission
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265508
VL  - 7
IS  - 47
ER  - 
TY  - JOUR
A1  - Gutknecht, Lise
A1  - Araragi, Naozumi
A1  - Merker, Sören
A1  - Waider, Jonas
A1  - Sommerlandt, Frank M. J.
A1  - Mlinar, Boris
A1  - Baccini, Gilda
A1  - Mayer, Ute
A1  - Proft, Florian
A1  - Hamon, Michel
A1  - Schmitt, Angelika G.
A1  - Corradetti, Renato
A1  - Lanfumey, Laurence
A1  - Lesch, Klaus-Peter
T1  - Impacts of Brain Serotonin Deficiency following Tph2 Inactivation on Development and Raphe Neuron Serotonergic Specification
JF  - PLoS One
N2  - Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2). Tph2 inactivation (Tph2-/-) resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT) demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT\(_{1A}\) and 5-HT\(_{1B}\) receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.
KW  - lacking
KW  - knock-out mice
KW  - energy expenditure
KW  - locomotor activity
KW  - 5-HT transporter
KW  - anxiety like
KW  - receptors
KW  - behavior
KW  - tryptophan
KW  - nucleus
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133728
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - van de Kerkhof, Nora WA
A1  - Fekkes, Durk
A1  - van der Heijden, Frank MMA
A1  - Hoogendijk, Witte JG
A1  - Stöber, Gerald
A1  - Egger, Jos IM
A1  - Verhoeven, Willem MA
T1  - Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia
JF  - Neuropsychiatric Disease and Treatment
N2  - Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia. Eighty patients referred for psychotic disorders were assessed with the Comprehensive Assessment of Symptoms and History, and (both at inclusion and after 6 weeks of antipsychotic treatment) with the Positive and Negative Syndrome Scale and Clinical Global Impression. From 58 completers, 33 patients were diagnosed with schizophrenia and ten with CP according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Leonhard criteria, respectively. Fifteen patients were diagnosed with other disorders within the psychosis spectrum. At both time points, blood levels of the dopamine metabolite homovanillic acid, brain-derived neurotrophic factor, and amino acids related to glutamate neurotransmission were measured and compared with a matched control sample. Patients with CP showed a significantly better response to antipsychotic treatment as compared to patients with schizophrenia. In CP, glycine levels were elevated and tryptophan levels were lowered as compared to schizophrenia. Glutamate levels were increased in both patient groups as compared to controls. These results, showing marked differences in both treatment outcome and glutamate-related variable parameters, may point at better neuroplasticity in CP, necessitating demarcation of this subgroup within the psychosis spectrum.
KW  - cycloid psychoses
KW  - schizophrenia
KW  - glutamate
KW  - glycine
KW  - tryptophan
KW  - neuroplasticity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166255
VL  - 12
ER  -