12997
2013
eng
e78238
10
8
article
1
2016-03-14
--
--
5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed.
While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice.
Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN.
Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM.
PLoS ONE
10.1371/journal.pone.0078238
urn:nbn:de:bvb:20-opus-129978
PLoS ONE 8(10): e78238. doi: 10.1371/journal.pone.0078238
Margherita M. Karabeg
Sandra Grauthoff
Sina Y. Kollert
Magdalena Weidner
Rebecca S. Heiming
Friederike Jansen
Sandy Popp
Sylvia Kaiser
Klaus-Peter Lesch
Norbert Sachser
Angelika G. Schmitt
Lars Lewejohann
eng
uncontrolled
immediate early genes
eng
uncontrolled
learning curves
eng
uncontrolled
animal performance
eng
uncontrolled
animal behavior
eng
uncontrolled
serotonin
eng
uncontrolled
learning
eng
uncontrolled
mice
eng
uncontrolled
hippocampus
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12997/090_5-HTT Deficiency.pdf
24273
2021
eng
14
10
article
1
--
2021-07-14
--
5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
Journal of Clinical Medicine
2077-0383
10.3390/jcm10143104
urn:nbn:de:bvb:20-opus-242739
2021-08-01T16:39:17+00:00
sword
swordwue
attachment; filename=deposit.zip
c26d74e7ca9ddb8ea8bed92f5c7da38f
Journal of Clinical Medicine 2021, 10(14), 3104; https://doi.org/10.3390/jcm10143104
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sandy Popp
Angelika Schmitt-Böhrer
Simon Langer
Ulrich Hofmann
Leif Hommers
Kai Schuh
Stefan Frantz
Klaus-Peter Lesch
Anna Frey
eng
uncontrolled
chronic heart failure
eng
uncontrolled
myocardial infarction
eng
uncontrolled
serotonin transporter deficient mice
eng
uncontrolled
anxiety
eng
uncontrolled
depression
eng
uncontrolled
behavior
eng
uncontrolled
inflammation
Medizin und Gesundheit
open_access
Physiologisches Institut
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Klinik und Poliklinik I
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24273/jcm-10-03104-v2.pdf
24522
2021
eng
9
12
article
1
--
2021-08-29
--
A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
Genes
2073-4425
10.3390/genes12091356
urn:nbn:de:bvb:20-opus-245220
2021-09-13T20:11:29+00:00
sword
swordwue
attachment; filename=deposit.zip
a5f7edb0ad4521f389b1d2ea6e31ca42
Genes 2021, 12(9), 1356; https://doi.org/10.3390/genes12091356
01EW1902
728018
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Georg C. Ziegler
Ann-Christine Ehlis
Heike Weber
Maria Rosaria Vitale
Johanna E. M. Zöller
Hsing-Ping Ku
Miriam A. Schiele
Laura I. Kürbitz
Marcel Romanos
Paul Pauli
Raffael Kalisch
Peter Zwanzger
Katharina Domschke
Andreas J. Fallgatter
Andreas Reif
Klaus-Peter Lesch
eng
uncontrolled
ADHD
eng
uncontrolled
CDH13
eng
uncontrolled
neurodevelopment
eng
uncontrolled
executive functions
eng
uncontrolled
working memory
eng
uncontrolled
Big Five
eng
uncontrolled
agreeableness
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Institut für Psychologie
OpenAIRE
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24522/genes-12-01356.pdf
12684
2012
eng
573-579
4
224
article
1
2016-02-10
--
--
A polymorphism in the gene of the endocannabinoid-degrading enzyme FAAH (FAAH C385A) is associated with emotional-motivational reactivity
RATIONALE:
The endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional-motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional-motivational reactivity is complex and bidirectional due to upcoming compensatory processes.
OBJECTIVES:
Therefore, we further investigated the relationship of the FAAH polymorphism and emotional-motivational reactivity in humans.
METHODS:
We assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers.
RESULTS:
Contrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence.
CONCLUSIONS:
Our findings emphasize the bidirectionality and thorough examination of the eCB system's impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders.
Psychopharmacology
10.1007/s00213-012-2785-y
urn:nbn:de:bvb:20-opus-126845
Psychopharmacology (2012) 224:573–579 DOI 10.1007/s00213-012-2785-y
Annette Conzelmann
Andreas Reif
Christian Jacob
Peter Weyers
Klaus-Peter Lesch
Beat Lutz
Paul Pauli
eng
uncontrolled
startle reflex
eng
uncontrolled
endocannabinoid
eng
uncontrolled
FAAH
eng
uncontrolled
genetics
eng
uncontrolled
emotion
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Institut für Psychologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12684/Conzelmann_2Fs00213-012-2785-y.pdf
12993
2012
eng
573-579
4
224
article
1
2016-03-14
--
--
A polymorphism in the gene of the endocannabinoid-degrading enzyme FAAH (FAAH C385A) is associated with emotional–motivational reactivity
Rationale
The endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional–motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional–motivational reactivity is complex and bidirectional due to upcoming compensatory processes.
Objectives
Therefore, we further investigated the relationship of the FAAH polymorphism and emotional–motivational reactivity in humans.
Methods
We assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers.
Results
Contrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence.
Conclusions
Our findings emphasize the bidirectionality and thorough examination of the eCB system’s impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders.
Psychopharmacology
10.1007/s00213-012-2785-y
urn:nbn:de:bvb:20-opus-129936
Psychopharmacology (2012) 224:573–579. DOI 10.1007/s00213-012-2785-y
Annette Conzelmann
Andreas Reif
Christian Jacob
Peter Weyers
Klaus-Peter Lesch
Beat Lutz
Paul Pauli
eng
uncontrolled
startle reflex
eng
uncontrolled
FAAH
eng
uncontrolled
genetics
eng
uncontrolled
endocannabinoid
eng
uncontrolled
emotion
Psychologie
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Institut für Pädagogik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12993/Conzelmann_10.1007-00213-012-2785-y.pdf
23996
2021
eng
1202
1219
10
62
article
1
--
--
--
Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets
Objective
Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.
Methods
We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.
Results
There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing.
Conclusion
Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
Journal of Child Psychology and Psychiatry
10.1111/jcpp.13396
urn:nbn:de:bvb:20-opus-239968
2021-06-14T19:55:59+00:00
sword
swordwue
attachment; filename=deposit.zip
889977a86151f79d4e7169c6ea5107af
Journal of Child Psychology and Psychiatry 2021, 62(10):1202-1219. DOI: 10.1111/jcpp.13396
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Merel C. Postema
Martine Hoogman
Sara Ambrosino
Philip Asherson
Tobias Banaschewski
Cibele E. Bandeira
Alexandr Baranov
Claiton H.D. Bau
Sarah Baumeister
Ramona Baur‐Streubel
Mark A. Bellgrove
Joseph Biederman
Janita Bralten
Daniel Brandeis
Silvia Brem
Jan K. Buitelaar
Geraldo F. Busatto
Francisco X. Castellanos
Mara Cercignani
Tiffany M. Chaim‐Avancini
Kaylita C. Chantiluke
Anastasia Christakou
David Coghill
Annette Conzelmann
Ana I. Cubillo
Renata B. Cupertino
Patrick de Zeeuw
Alysa E. Doyle
Sarah Durston
Eric A. Earl
Jeffery N. Epstein
Thomas Ethofer
Damien A. Fair
Andreas J. Fallgatter
Stephen V. Faraone
Thomas Frodl
Matt C. Gabel
Tinatin Gogberashvili
Eugenio H. Grevet
Jan Haavik
Neil A. Harrison
Catharina A. Hartman
Dirk J. Heslenfeld
Pieter J. Hoekstra
Sarah Hohmann
Marie F. Høvik
Terry L. Jernigan
Bernd Kardatzki
Georgii Karkashadze
Clare Kelly
Gregor Kohls
Kerstin Konrad
Jonna Kuntsi
Luisa Lazaro
Sara Lera‐Miguel
Klaus‐Peter Lesch
Mario R. Louza
Astri J. Lundervold
Charles B Malpas
Paulo Mattos
Hazel McCarthy
Leyla Namazova‐Baranova
Rosa Nicolau
Joel T. Nigg
Stephanie E. Novotny
Eileen Oberwelland Weiss
Ruth L. O'Gorman Tuura
Jaap Oosterlaan
Bob Oranje
Yannis Paloyelis
Paul Pauli
Felipe A. Picon
Kerstin J. Plessen
J. Antoni Ramos‐Quiroga
Andreas Reif
Liesbeth Reneman
Pedro G.P. Rosa
Katya Rubia
Anouk Schrantee
Lizanne J.S. Schweren
Jochen Seitz
Philip Shaw
Tim J. Silk
Norbert Skokauskas
Juan C. Soliva Vila
Michael C. Stevens
Gustavo Sudre
Leanne Tamm
Fernanda Tovar‐Moll
Theo G.M. van Erp
Alasdair Vance
Oscar Vilarroya
Yolanda Vives‐Gilabert
Georg G. von Polier
Susanne Walitza
Yuliya N. Yoncheva
Marcus V. Zanetti
Georg C. Ziegler
David C. Glahn
Neda Jahanshad
Sarah E. Medland
Paul M. Thompson
Simon E. Fisher
Barbara Franke
Clyde Francks
eng
uncontrolled
attention‐deficit
eng
uncontrolled
hyperactivity disorder
eng
uncontrolled
brain asymmetry
eng
uncontrolled
brain laterality
eng
uncontrolled
structural MRI
eng
uncontrolled
large‐scale data
Medizin und Gesundheit
open_access
Institut für Psychologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23996/Postema_Child_Psychology.pdf
13374
2011
eng
e20567
6
6
article
1
2016-05-20
--
--
Antidepressant Drugs Transactivate TrkB Neurotrophin Receptors in the Adult Rodent Brain Independently of BDNF and Monoamine Transporter Blockade
Background:
Antidepressant drugs (ADs) have been shown to activate BDNF (brain-derived neurotrophic factor) receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands.
Methodology:
In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines.
Principal Findings:
Using a chemical-genetic TrkB(F616A) mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf(-/-) knock-out mice (132.4+/-8.5% of control; P = 0.01), indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT) deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB.
Conclusions:
The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the ability of ADs to induce TrkB activity in brain.
PLoS ONE
10.1371/journal.pone.0020567
urn:nbn:de:bvb:20-opus-133746
PLoS ONE 6(6): e20567. doi:10.1371/journal.pone.0020567
false
true
Tomi Rantamäki
Liisa Vesa
Hanna Antila
Antonio Di Lieto
Päivi Tammela
Angelika Schmitt
Klaus-Peter Lesch
Maribel Rios
Eero Castrén
eng
uncontrolled
Serotonin transporter
eng
uncontrolled
Neuronal plasticity
eng
uncontrolled
Mood disorders
eng
uncontrolled
Messenger-RNA
eng
uncontrolled
Mouse-brain
eng
uncontrolled
Rat-brain
eng
uncontrolled
Activation
eng
uncontrolled
Depression
eng
uncontrolled
Mice
eng
uncontrolled
Insensitivity
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13374/011_Rantamaeki_PLoS-ONE.pdf
15821
2017
eng
9498247
article
1
2018-02-27
--
--
Autism-like behaviours and memory deficits result from a Western Diet in mice
Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.
Neural Plasticity
10.1155/2017/9498247
urn:nbn:de:bvb:20-opus-158211
Neural Plasticity, 9498247 (2017). DOI: 10.1155/2017/9498247
602805
677302
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Ekaterina Veniaminova
Raymond Cespuglio
Chi Wai Cheung
Alexei Umriukhin
Nataliia Markova
Elena Shevtsova
Klaus-Peter Lesch
Daniel C. Anthony
Tatyana Strekalova
eng
uncontrolled
diet
eng
uncontrolled
autism-like behavior
eng
uncontrolled
mice
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15821/Veniaminova_Neural_Plasticity.pdf
14372
2015
eng
47
9
article
1
2017-02-02
--
--
Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype
Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety like behavior ("allostatic load"). The alternative "mismatch hypothesis" suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HIT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered.
Frontiers in Behavioral Neuroscience
10.3389/fnbeh.2015.00047
urn:nbn:de:bvb:20-opus-143723
Frontiers in Behavioral Neuroscience 9:47 (2015). DOI: 10.3389/fnbeh.2015.00047
602805
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Carina Bodden
S. Helene Richter
Rebecca S. Schreiber
Vanessa Kloke
Joachim Gerß
Rupert Palme
Klaus-Peter Lesch
Lars Lewejohann
Sylvia Kaiser
Norbert Sachser
eng
uncontrolled
anxiety-like behavior
eng
uncontrolled
maternal care
eng
uncontrolled
dangerous world
eng
uncontrolled
animal behavior
eng
uncontrolled
match-mismatch
eng
uncontrolled
chronic social stress
eng
uncontrolled
elevated plus-maze
eng
uncontrolled
5-HTT
eng
uncontrolled
life history
eng
uncontrolled
predictive adaptive response hypothesis
eng
uncontrolled
developmental plasticity
eng
uncontrolled
knockout mice
eng
uncontrolled
environmental enrichment
eng
uncontrolled
allostatic load
Medizin und Gesundheit
open_access
Lehrstuhl für Molekulare Psychiatrie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14372/Bodden_Frontiers_in_Behavioural_Neuroscience.pdf
16517
2016
eng
370
10
article
1
2018-07-20
--
--
Brain-Derived Neurotrophic Factor (Val66Met) and Serotonin Transporter (5-HTTLPR) Polymorphisms Modulate Plasticity in Inhibitory Control Performance Over Time but Independent of Inhibitory Control Training
Several studies reported training-induced improvements in executive function tasks and also observed transfer to untrained tasks. However, the results are mixed and there is a large interindividual variability within and across studies. Given that training-related performance changes would require modification, growth or differentiation at the cellular and synaptic level in the brain, research on critical moderators of brain plasticity potentially explaining such changes is needed. In the present study, a pre-post-follow-up design (N = 122) and a 3-weeks training of two response inhibition tasks (Go/NoGo and Stop-Signal) was employed and genetic variation (Val66Met) in the brain-derived neurotrophic factor (BDNF) promoting differentiation and activity-dependent synaptic plasticity was examined. Because Serotonin (5-HT) signaling and the interplay of BDNF and 5-HT are known to critically mediate brain plasticity, genetic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) was also addressed. The overall results show that the kind of training (i.e., adaptive vs. non-adaptive) did not evoke genotype-dependent differences. However, in the Go/NoGo task, better inhibition performance (lower commission errors) were observed for BDNF Val/Val genotype carriers compared to Met-allele ones supporting similar findings from other cognitive tasks. Additionally, a gene-gene interaction suggests a more impulsive response pattern (faster responses accompanied by higher commission error rates) in homozygous l-allele carriers relative to those with the s-allele of 5-HTTLPR. This, however, is true only in the presence of the Met-allele of BDNF, while the Val/Val genotype seems to compensate for such non-adaptive responding. Intriguingly, similar results were obtained for the Stop-Signal task. Here, differences emerged at post-testing, while no differences were observed at T1. In sum, although no genotype-dependent differences between the relevant training groups emerged suggesting no changes in the trained inhibition function, the observed genotype-dependent performance changes from pre- to post measurement may reflect rapid learning or memory effects linked to BDNF and 5-HTTLPR. In line with ample evidence on BDNF and BDNF-5-HT system interactions to induce (rapid) plasticity especially in hippocampal regions and in response to environmental demands, the findings may reflect genotype-dependent differences in the acquisition and consolidation of task-relevant information, thereby facilitating a more adaptive responding to task-specific requirements.
Frontiers in Human Neuroscience
10.3389/fnhum.2016.00370
urn:nbn:de:bvb:20-opus-165176
Front. Hum. Neurosci. 10:370.
false
true
Sören Enge
Monika Fleischhauer
Anne Gärtner
Andreas Reif
Klaus-Peter Lesch
Matthias Kliegel
Alexander Strobel
eng
uncontrolled
executive function training
eng
uncontrolled
response inhibition
eng
uncontrolled
neuronal plasticity
eng
uncontrolled
BDNF Val66Met
eng
uncontrolled
5-HTTLPR
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16517/053_Enge_FRONTIERS IN HUMAN NEUROSCIENCE.pdf