Synaptic vesicle dynamic changes in a model of fragile X

__Background:__ Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. __Methods:__ Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MSE) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. __Results:__ Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. __Conclusions:__ Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS

Clinician’s perceptions of and emotional responses to online infidelity

Aim of the present study was to examine the degree to which mental health workers perceive twelve online partner behaviors as different types of infidelity and to examine the degree to which these behaviors evoke two types of jealousy, that is, fait accompli and anxious jealousy among mental. 248 heterosexual mental health workers filled out an online questionnaire describing twelve potentially unfaithful online partner behaviors, assessing perceptions of types of infidelity and types of jealousy. Results showed that participants viewed most partner behaviors consistent with a priori expectations regarding their sexual and emotional nature. Interestingly, 65% of the participants thought that a partner watching porn on the Internet did not engage in any form of infidelity. In addition, most scenarios evoked more fait accompli jealousy than anxious jealousy. Age and gender differences are discussed, as well as implications of these findings for the treatment of jealous

Synaptic vesicle dynamic changes in a model of fragile X

BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. METHODS: Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. RESULTS: Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. CONCLUSIONS: Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS

Additional file 1: of Synaptic vesicle dynamic changes in a model of fragile X

Supplementary methods information, figures of principal component analysis (PCA), GO term analysis heatmap, live-cell imaging setup and number of synaptic boutons, and tables with a full list of significant changed proteins in mouse brain tissue and synaptosome fractions in LC-MSE and GO term enrichment results. (DOCX 405 kb