Biology subjects

Meijer, M.

Publications and source records attributed to Meijer, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Balancing spatial resolution and proteome depth in LC-MS based spatialproteomics

Spatial proteomics aims to resolve protein composition within intact tissues, yet extraction-based liquid chromatography-mass spectrometry (LC-MS) workflows face an inherent trade-off: smaller sampling units increase spatial specificity, whereas larger sampling units provide greater proteome depth and robustness. As analytical sensitivity improves, sampling-unit size therefore becomes a key experimental design parameter. Current extraction-based LC-MS workflows typically rely on laser capture microdissection (LCM), where sample recovery and scalability can become limiting at low input. Spatially resolved laser-activated cell sorting (SLACS) offers an alternative tissue-isolation strategy based on single-pulse near-infrared laser activation. Here, we use SLACS to systematically examine the resolution-sensitivity trade-off across sampling units ranging from single-cell-equivalent to larger low-input tissue regions. Few-cell sampling retained substantial proteomic information relative to larger regions while increasing spatial specificity. Applied to the mouse somatosensory cortex, SLACS generated deep, layer-resolved proteomic profiles from regions corresponding to approximately 60 cells and preserved major layer-specific molecular patterns at inputs as low as approximately 6 cells. These results highlight sampling-unit size as an important experimental design parameter in extraction-based spatial proteomics and support few-cell sampling as a practical compromise between spatial specificity, proteome depth and robustness.

biochemistry↗

bioRxiv2025

Leaping over the blood-brain barrier: DNA methylation as a link between peripheral and central immune systems

AbstractMost existing DNA methylation (DNAm) studies have used peripheral surrogate tissues to research molecular mechanisms underlying brain disorders and diseases. Initial studies comparing brain to blood primarily at the individual CpG level analysis have generally pointed to a limited overlap of epigenetic patterns, consistent with DNAm being largely tissue- and even cell type-specific. Expanding on these studies, we employed a more complex analysis strategy aimed to 1) identify single DNAm sites associated with deconvolution-estimated brain cell type proportions, the principal measure in this study, in both the frontal brain and peripheral blood, 2) combine blood DNAm sites to predict brain cell type proportions through multivariate models, and 3) examine the association of blood DNAm, age, and epigenetic age acceleration (EAA) on brain cell type proportions. Epigenome-wide association studies for seven brain cell type proportions in matched frontal brain and peripheral blood samples (n=104) revealed that [~]10% of brain cell type-associated DNAm sites had correlating DNAm levels in peripheral blood (p<0.05). However, only three peripheral blood DNAm sites were significantly associated with endothelial and stromal brain cell type proportions (adjusted p<0.05). Brain cell type proportion predictions trained with machine learning approaches using peripheral blood DNAm showed the strongest, although still modest correlations with microglia proportions estimated through cell deconvolution using brain DNAm. Further, deconvolution- estimated blood immune cell type proportions showed a nominally significant association with estimated brain stromal cell proportions, driven primarily by NK cells; however, this association was dependent on chronological age and did not survive age-residualization. Lastly, brain EAA was not associated with brain and blood cell type proportions (adjusted p<0.05). Collectively, these results suggested that in the context of broad tissue-specificity of DNAm patterns, DNAm levels in peripheral blood might actually inform on some immune brain cell type proportions. The correlations between DNAm profiles specific to immune cell types in blood and brain were consistent with a potential link between peripheral immune and central nervous system immune functions.

neuroscience↗

bioRxiv2025

Multi-omics Profiling of the Lateral Ventricle Choroid Plexus Reveals Developmental Cellular Remodeling, Early Immune Gene Activation, and a Novel Epithelial Subtype

Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis--including bulk and single-cell transcriptomics and epigenomics--of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking changes in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune cells were markedly increased in adulthood and immune cell profiling revealed an altered cell-type diversity through time. Surprisingly, we observed an early gene activation of host-defense genes in all choroid plexus main cell types, beginning in the neonatal period and progressively increasing into young adulthood. Moreover, some genes induced in epithelial cells in response to inflammation were found to be epigenetically primed, despite not being transcriptionally active. Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a novel epithelial cell subtype with unique gene markers suggesting a specialized function potentially linked to neuro-signaling. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during choroid plexus maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of transcriptional activity and chromatin accessibility in choroid plexus cells, providing a valuable resource to guide future efforts in targeting gene expression at the choroid plexus for therapeutical purposes.

neuroscience↗

bioRxiv2024

Considerations for Cell Type Heterogeneity in Pediatric Salivary DNA Methylation Analyses: Comparison of Reference Panels & Stratification by Estimated Cell TypeProportion

Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. Given DNAms integral role to cellular differentiation and maintenance, DNAm profiles are often highly cell type (CT)-specific and CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), discrepancy between chronological age and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistically adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels--constructed from adult versus pediatric samples--affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, has yet to be examined. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results highlighted the impact of estimated CT discrepancies across child and adult reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples--primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the context of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.

bioinformatics↗

bioRxiv2024

Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate

Malaria transmission-blocking vaccines (TBV) target sexual stage parasites that are transmitted to mosquitoes and critical for spread of the pathogen. The clinically most advanced TBV candidate contains part of the Pro-domain (Pro) and Domain 1 (D1) of Plasmodium falciparum surface protein Pfs230. Subunit vaccines that contain other domains of Pfs230 have so far failed to induce functional antibodies. Here, we produced eight single domain fragments of Pfs230 in Drosophila melanogaster S2 cells and assessed their immunogenicity in mouse immunizations. In addition to D1-specific antibodies, antibodies raised against Domain 12 (D12) showed strong recognition of Pfs230 on the surface of female parasites. Importantly, D12-specific antibodies showed strong functional transmission-reducing activity in membrane feeding assays with cultured parasites, an activity that was complement-dependent. Murine D12-specific antibodies further reduced mosquito transmission of parasites acquired from naturally infected parasite carriers. The D12 antigen was recognized by sera from an all-age cohort of individuals who had been naturally exposed to Plasmodium falciparum with antibody levels increasing with age. In conclusion, we identified Pfs230D12 as a promising new TBV candidate. Impact statementPfs230 Domain 12 induces antibodies in mice that strongly reduce transmission of lab-cultured and naturally circulating malaria parasites to mosquitoes.

immunology↗

bioRxiv2024

Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs

The adult human central nervous system (CNS) is remarkably complex, with neural cells displaying extensive transcriptional heterogeneity. However, how different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here, we profile the adult human CNS from distinct regions, for chromatin accessibility at the single-nuclei level. In addition, we simultaneously co-profiled the histone modifications H3K27me3 and H3K27ac at the single nuclei-level, providing their first map in all major human CNS cell types. We unveil primed chromatin signatures at HOX loci in spinal cord-derived human oligodendroglia (OLG) but not microglia. These signatures were reminiscent of developmental OLG but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem cell (iPS) derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, and bears a strong resemblance not only to OLG developmental architecture, but also high-grade pontine gliomas. Thus, adult OLG retain epigenetic memory from developmental states, which might enable them to promptly transcribe Hox genes, in contexts of regeneration, but also make them susceptible to gliomagenesis.

neuroscience↗

bioRxiv2024

Identification of regional astrocyte heterogeneity associated with cuprizone-induced de- and remyelination using spatial transcriptomics

The cuprizone model is a well-characterized model to study processes of demyelination and remyelination, which are known features of multiple sclerosis. Cuprizone induces oligodendrocyte loss and severe demyelination in the brain, including the corpus callosum, hippocampus, and cortex. Loss of oligodendrocytes and myelin is accompanied by microgliosis and astrogliosis, wherein microglia and astrocytes partially lose their homeostatic functions and acquire a reactive/activated state. Cuprizone-induced demyelination peaks later in grey matter (GM) than in white matter (WM), and remyelination is more efficient in WM areas. Here, we aim to better understand regional diversity in microglia, astrocytes, and oligodendrocytes and their respective role in remyelination efficiency, by characterizing their response to cuprizone across brain regions. We applied spatial transcriptomics (ST) for unbiased gene activity profiling of multiple brain regions in a single tissue section, to identify region-associated changes in gene activity following cuprizone treatment. Gene activity changes were detected in highly abundant cell types, like neurons, oligodendrocytes, and astrocytes, but challenging to detect in low-abundant cell types such as microglia and oligodendrocyte precursor cells. ST revealed a significant increase in the expression of astrocyte markers Clu, Slc1a3, and Gfap during the demyelination phase in the WM fiber tract. In the cortex, the changes in GFAP expression were less prominent, both at the transcriptional and protein level. By mapping genes obtained from scRNAseq of FACS-sorted ACSA2-positive astrocytes onto the ST data, we observed astrocyte heterogeneity beyond the simple classification of WM- and GM-astrocytes in both control and cuprizone-treated mice. In the future, the characterization of these regional astrocyte populations could aid the development of novel strategies to halt the progression of demyelination and support remyelination. Highlights Astrocyte markers Clu, Slc1a3, and Gfap are increased in WM fiber tracts during demyelination Expression dynamics of astrogliosis markers Gfap and Vim during de-and remyelination depend on the brain region Combining scRNAseq with ST data revealed astrocyte heterogeneity beyond WM- and GM-differences scRNAseq-identified gene sets were differently affected by cuprizone treatment across brain regions

neuroscience↗

bioRxiv2023

Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are transcriptionally heterogeneous and can transition to immune-like states in the context of MS. However, the intricacies of their dynamics throughout disease progression remain poorly understood. Here, we employed simultaneous single-cell multiome ATAC and RNA sequencing targeting oligodendroglia (OLGs) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at different stages of the disease course. We found that the transition to immune OLG states appear already at the early stages of EAE and persist to the late stages of the disease. Interestingly, transcription factor activity suggested immunosuppression in MOLs at early stages of EAE and we also observed a transitory activation of a regenerative program in MOLs at this stage. Importantly, different MOLs exhibit a differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/6. Moreover, we observed divergent responses at the epigenetic level of MOL2 and MOL5/6 during disease evolution. Thus, our single-cell multiomic resource highlights dynamic and distinct responses of OLG subpopulations to the evolving environment in EAE, which might modulate their response to regenerative therapeutic interventions in MS.

neuroscience↗

bioRxiv2023

Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes

Tomosyns are soluble SNARE proteins proposed to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario using a novel mouse model, energy barrier recordings, and single-molecule force measurements. Tomosyn-1/2 deficiency drastically enhanced the probability that synaptic vesicles fuse at synapses, resulting in stronger synapses with faster depression and slower recovery. While wildtype tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Force measurements revealed that tomosyns SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that regions outside the SNARE motif contribute to tomosyns inhibitory function. These results reveal that tomosyns regulate synaptic transmission by preventing SNAP-25 binding to template complexes, increasing the energy barrier for synaptic vesicle fusion, and limiting synaptic depression.

neuroscience↗

bioRxiv2023

A human in vitro neuronal model for studying homeostatic plasticity at the network level

Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell level; this platform can be extended to investigate altered homeostatic plasticity in brain disorders.

neuroscience↗

bioRxiv2021

Brain macrophages acquire distinct transcriptomes prior to demyelination in multiple sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed an early stress response in brain macrophages in NAWM and identified specific macrophage subsets that associate with different stages of demyelinating lesions. These early changes associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination.

neuroscience↗

bioRxiv2021

Developmental landscape of human forebrain at a single-cell level unveils early waves of oligodendrogenesis

Oligodendrogenesis in the human central nervous system has been mainly observed at the second trimester of gestation, a much later developmental stage compared to mouse. Here we characterize the transcriptomic neural diversity in the human forebrain at post conceptual weeks (PCW) 8 to 10, using single-cell RNA-Seq. We find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level with single-cell ATAC-Seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of fifty key genes using In Situ Sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mouse and human and describe regulatory mechanisms required for human OPC specification.

neuroscience↗

bioRxiv2020

Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

Previously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1 dependent and independent mechanisms that lower the energy barrier independently in an additive manner to produce PTP by multiplication of release rates.

neuroscience↗

bioRxiv2020

A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis

Multiple sclerosis (MS) is a disease characterized by a targeted immune attack on myelin in the central nervous system (CNS). We have previously shown that oligodendrocytes (OLs), myelin producing cells in the CNS, and their precursors (OPCs), ac-quire disease-specific transcriptional states in MS 1,2. To under-stand how these alternative transcriptional programs are acti-vated in disease, we performed single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) on the OL lineage in the experimental autoimmune encephalomyeli-tis (EAE) mouse model of MS. We identified regulatory regions with increased accessibility in oligodendroglia (OLG) in EAE, some of which in the proximity of immune genes. A similar re-modeling of chromatin accessibility was observed upon treat-ment of postnatal OPCs with interferon-gamma (IFN{gamma}), but not with dexamethasone. These changes in accessibility were not exclusive to distal enhancers, but also occurred at promoter re-gions, suggesting a role for promoters in mediating cell-state transitions. Notably, we found that a subset of immune genes al-ready exhibited chromatin accessibility in OPCs ex vivo and in vivo, suggesting a primed chromatin state in OLG compatible with rapid transitions to an immune-competent state. Several primed genes presented bivalency of H3K4me3 and H3K27me3 at promoters in OPCs, with loss of H3K27me3 upon IFN{gamma} treatment. Inhibition of JMJD3/Kdm6b, mediating removal of H3K27me3, led to the inability to activate these genes upon IFN{gamma} treatment. Importantly, OLGs from the adult human brain showed chromatin accessibility at immune gene loci, par-ticularly at MHC-I pathway genes. A subset of single-nucleotide polymorphisms (SNPs) associated with MS susceptibility over-lapped with these primed regulatory regions in OLG from both mouse and human CNS. Our data suggest that susceptibility for MS may involve activation of immune gene programs in OLG. These programs are under tight control at the chromatin level in OLG and may therefore constitute novel targets for immunological-based therapies for MS.

neuroscience↗

bioRxiv2020

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2x10-7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

genetics↗

bioRxiv2020

Cell-type specialization in the brain is encoded by specific long-range chromatin topologies

Neurons and oligodendrocytes are terminally differentiated cells that sustain cascades of gene activation and repression to execute highly specialized functions, while retaining homeostatic control. To study long-range chromatin folding without disturbing the native tissue environment, we developed Genome Architecture Mapping in combination with immunoselection (immunoGAM), and applied it to three cell types from the adult murine brain: dopaminergic neurons (DNs) from the midbrain, pyramidal glutamatergic neurons (PGNs) from the hippocampus, and oligodendroglia (OLGs) from the cortex. We find cell-type specific 3D chromatin structures that relate with patterns of gene expression at multiple genomic scales, including extensive reorganization of topological domains (TADs) and chromatin compartments. We discover the loss of TAD insulation, or TAD melting, at long genes (>400 kb) when they are highly transcribed. We find many neuron-specific contacts which contain accessible chromatin regions enriched for putative binding sites for multiple neuronal transcription factors, and which connect cell-type specific genes that are associated with neurodegenerative disorders such as Parkinsons disease, or specialized functions such as synaptic plasticity and memory. Lastly, sensory receptor genes exhibit increased membership in heterochromatic compartments that establish strong contacts in brain cells. However, their silencing is compromised in a subpopulation of PGNs with molecular signatures of long-term potentiation. Overall, our work shows that the 3D organization of the genome is highly cell-type specific, and essential to better understand mechanisms of gene regulation in highly specialized tissues such as the brain.

molecular biology↗

bioRxiv2019

BRAin INteractive Sequencing Analysis Tool (BRAIN-SAT); facilitating interactive transcriptome analyses (http://brainsat.eu/)

Over the last decade, a large number of glia transcriptome studies has been published. New technologies and platforms have been developed to allow access and interrogation of the published data. The increase in large transcriptomic data sets allows for innovative in silico analyses to address biological questions. Here we present BRAIN-SAT, the follow-up of our previous database GOAD, with several new features available on an interactive platform that enables access to recent, high quality bulk and single cell RNA-Seq data. The combination of several functions including gene searches, differential and quantitative expression analysis and a single cell expression analysis feature enables the exploration of published data sets at different levels. These different functionalities can be used for researchers and research companies in the neuroscience field to evaluate and visualize gene expression levels in a set of relevant publications. Here, we present a new platform with easy access to published gene expression studies for data exploration and gene of interest searches.

neuroscience↗

bioRxiv2019

Molecular characterization of the stress network in the human brain

The biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of neural stress sensitivity. Linking mRNA expression data from the Allen Human Brain Atlas to task-based fMRI revealed 201 differentially expressed genes in cortex-specific brain regions differentially activated by stress in individuals with low or high stress sensitivity. These genes are associated with stress-related psychiatric disorders (e.g. schizophrenia and anxiety) and include markers for specific neuronal populations (e.g. ADCYAP1, GABRB1, SSTR1, and TNFRSF12A), neurotransmitter receptors (e.g. GRIN3A, SSTR1, GABRB1, and HTR1E), and signaling factors that interact with the corticosteroid receptor and hypothalamic-pituitary-adrenal axis (e.g. ADCYAP1, IGSF11, and PKIA). Overall, the identified genes potentially underlie altered stress reactivity in individuals at risk for psychiatric disorders and play a role in mounting an adaptive stress response, making them potentially druggable targets for stress-related diseases.

neuroscience↗