Biology subjects

Bresser, T.

Publications and source records attributed to Bresser, T..

3 recordsLinked to original sources

bioRxiv2024

Multimodal brain imaging of insomnia, depression and anxiety symptoms: transdiagnostic commonalities and differences

Insomnia disorder, major depressive disorder and anxiety disorders are the most common mental health conditions, with high comorbidity and genetic overlap suggesting shared brain mechanisms. Studies on brain correlates of these disorders have not fully addressed this overlap. Aiming to distinguish shared from specific brain structural and functional properties associated with symptoms of these disorders, this study analyzed multimodal brain imaging data from over 40,000 UK Biobank participants. Functional enrichment analyses were conducted to understand the cognitive-emotional and neurotransmission implications of the identified brain regions and connections. Results showed that smaller cortical surfaces, smaller thalamic volumes, and weaker functional connectivity were linked to more severe symptoms across all symptom types. Several symptom-specific associations were revealed, most commonly in different parts of the amygdala-hippocampal-medial prefrontal circuit. These findings revealed both transdiagnostically shared and unique brain properties that could lead to more directed treatment targets for insomnia, depression, and anxiety.

neuroscience↗

bioRxiv2023

Insomnia subtypes have differentiating deviations in brain structural connectivity

ObjectiveInsomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes. MethodsStructural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of personality and mood traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age, sex, and brain volume evaluated group differences in structural connectivity strength, indicated by fractional anisotropy and mean diffusivity, and evaluated within two different atlases. ResultsInsomnia subtypes showed differentiating profiles of deviating structural connectivity which moreover concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed (p=0.019), moderately distressed reward insensitive (p=0.014), slightly distressed low reactive (p=0.006) and slightly distressed high reactive (p=0.006). ConclusionsOur results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.

neuroscience↗

bioRxiv2017

Molecular pathway underlying bouton stabilization by Semaphorin4D during inhibitory synapse formation

Changes in inhibitory connections are essential for experience-dependent circuit adaptations. Defects in inhibitory synapses are linked to neurodevelopmental disorders, but the molecular processes underlying inhibitory synapse formation are not well understood. Here we use high resolution two-photon microscopy in organotypic hippocampal slices to examine the signaling pathways induced by the postsynaptic signaling molecule Semaphorin4D (Sema4D) during inhibitory synapse formation. By monitoring changes in individual GFP-labeled presynaptic boutons we found that the primary action of Sema4D is to induce stabilization of presynaptic boutons within tens of minutes. Stabilizing boutons rapidly recruited synaptic vesicles, which was followed by accumulation of postsynaptic gephyrin. Newly formed inhibitory synapses were complete and functional after 24 hours, as determined by electrophysiology and immunohistochemistry. We further showed that Sema4D signaling is regulated by network activity and can induce a local increase in bouton density, suggesting a possible role in circuit adaptation. We further examined the intracellular signaling cascade triggered by Sema4D and found that bouton stabilization occurred through rapid remodeling of actin, and this could be mimicked by the actin-depolymerizing drug Latrunculin B or by reducing ROCK activity. The intracellular signaling cascade required activation of the receptor tyrosine kinase MET, which is a well-known autism risk factor. Our immunohistochemistry data suggests that MET may be localized to presynaptic inhibitory axons. Together, our data yield important insights in the molecular pathway underlying activity-dependent Sema4D-induced synapse formation and reveal a novel role for MET in inhibitory synapses.\n\nSignificance StatementGABAergic synapses provide the main inhibitory control of neuronal activity in the brain. We make important steps in unraveling the molecular processes that take place when formation of inhibitory synapses is triggered by a specific signaling molecule, Sema4D. We find that this process depends on network activity and involves specific remodeling of the intracellular actin cytoskeleton. We also reveal a previously unknown role for MET in inhibitory synapses. As defects in GABAergic synapses have been implied in many brain disorders, and mutations in MET are strong risk factors for autism, our findings urge for a further investigation of the role of MET at inhibitory synapses.

neuroscience↗