Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action.

Origin and distribution pattern of pelvic limb nerves of a Bengal tiger (Panthera tigris tigris).

The Bengal tiger (Panthera tigris tigris) is a species belonging to the Felidae family. In Argentina, tigers are currently only found in captivity. The longevity of individual animals in human-controlled environments depends on proper management and practices that prioritize animal welfare.

Sex and cell-specific gene expression in corticolimbic brain regions associated with psychiatric disorders revealed by bulk and single-nuclei RNA sequencing.

Background: There are sex-specific differences in the prevalence, symptomology and course of psychiatric disorders. However, preclinical models have primarily used males, such that the molecular mechanisms underlying sex-specific differences in psychiatric disorders are not well established.

Methods: In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala (n = 22-24 per group/region).

A Glucocorticoid-Sensitive Hippocampal Gene Network Moderates the Impact of Early-Life Adversity on Mental Health Outcomes.

Background: Early stress increases the risk for psychiatric disorders. Glucocorticoids are stress mediators that regulate transcriptional activity and morphology in the hippocampus, which is implicated in the pathophysiology of multiple psychiatric conditions. We aimed to establish the relevance of hippocampal glucocorticoid-induced transcriptional activity as a mediator of the effects of early life on later psychopathology in humans.

Integrative multi-omics landscape of fluoxetine action across 27 brain regions reveals global increase in energy metabolism and region-specific chromatin remodelling.

Depression and anxiety are major global health burdens. Although SSRIs targeting the serotonergic system are prescribed over 200 million times annually, they have variable therapeutic efficacy and side effects, and mechanisms of action remain incompletely understood. Here, we comprehensively characterise the molecular landscape of gene regulatory changes associated with fluoxetine, a widely-used SSRI.

Brain-Derived Neurotrophic Factor in the Nucleus Accumbens Mediates Individual Differences in Behavioral Responses to a Natural, Social Reward.

BDNF-oxytocin interactions in the brain are implicated in mammalian maternal behavior. We found that BDNF gene expression is increased in the hippocampus of rat mothers that show increased pup licking/grooming (high LG mothers) compared to low LG mothers. High LG mothers also showed increased BDNF protein levels in the nucleus accumbens (nAcc).

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions.

Background: Activation of brain insulin receptors modulates reward sensitivity, inhibitory control and memory. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related mental disorders (attention deficit hyperactivity disorder or ADHD, addiction, dementia), in agreement with the high co-morbidity between insulin resistance and psychopathology. These neurobiological mechanisms can be explored using genetic studies.

Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts.

Individuals born after intrauterine growth restriction (IUGR) are more impulsive towards palatable foods, but it is not clear 1) if IUGR-related impulsivity is specific for foods and solely based on response inhibition and 2) if the development of impulsivity is due to being born IUGR per se or to growing up fast in the first few years of life (catch up growth). Children were classified in the IUGR group if the birth weight ratio was below 0.85.

Production and analysis of a Bacillus subtilis biofilm comprised of vegetative cells and spores using a modified colony biofilm model.

Bacillus subtilis is a spore-forming soil bacterium that is capable of producing robust biofilms. Sporulation can occur in B. subtilis biofilms and it is possible that the spores embedded in the protective matrix could present a significant challenge to disinfecting agents or processes.

Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus.

Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG.

DNA methylome variation in a perinatal nurse-visitation program that reduces child maltreatment: a 27-year follow-up.

This study reveals the influence of child maltreatment on DNA methylation across the genome and provides the first evidence that a psychosocial intervention program, the Nurse Family Partnership (NFP), which targets mothers at risk for abusive parenting, associates with variation in the DNA methylome in adult offspring. The 188 participants were born to women randomly assigned to control (n = 99) or nurse-visited intervention groups (n = 89) and provided blood samples and a diagnostic interview at age 27 years. Interindividual variation in the blood DNA methylome was described using principal components (PC) scores derived from principal component analysis and showed that the NFP program (PC10: p = 0.

Dynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months.

Background: Fetal adversity, evidenced by poor fetal growth for instance, is associated with increased risk for several diseases later in life. Classical cut-offs to characterize small (SGA) and large for gestational age (LGA) newborns are used to define long term vulnerability. We aimed at exploring the possible dynamism of different birth weight cut-offs in defining vulnerability in developmental outcomes (through the Bayley Scales of Infant and Toddler Development), using the example of a gene vs.

Maternal care associates with differences in morphological complexity in the medial preoptic area.

The medial preoptic area (MPOA) is implicated in the expression of maternal behavior including the frequency of pup licking/grooming (LG) in the rat. Cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) is a transcription factor that regulates the expression of many genes. We found that lactating rats that are more maternal towards their pups showing increased licking/grooming (i.

Neuroanatomic Differences Associated With Stress Susceptibility and Resilience.

Background: We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging and diffusion tensor imaging to determine neuroanatomic differences between stress-susceptible and resilient mice. We also examined synchronized anatomic differences between brain regions to gain insight into the plasticity of neural networks underlying stress susceptibility.

Methods: C57BL/6 mice underwent 10 days of social defeat stress and were subsequently tested for social avoidance.

Maternal care differentially affects neuronal excitability and synaptic plasticity in the dorsal and ventral hippocampus.

Variations in early life maternal care modulate hippocampal development to program distinct emotional-cognitive phenotypes that persist into adulthood. Adult rat offspring that received low compared with high levels of maternal licking and grooming (low LG offspring) in early postnatal life show reduced long term potentiation (LTP) and impaired hippocampal-dependent memory, suggesting a 'detrimental' maternal effect on neural development. However, these studies focused uniquely on the dorsal hippocampus.

The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor.

Variations in maternal care in the rat influence the epigenetic state and transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus. The mechanisms underlying this maternal effect remained to be defined, including the nature of the relevant maternally regulated intracellular signalling pathways. We show here that increased maternal licking/grooming (LG), which stably enhances hippocampal GR expression, paradoxically increases hippocampal expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to the exon 17 GR promoter.

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel.

Background: Platelet inhibitors are commonly used to reduce the risk of atherothrombotic events. The aim of this study was to determine the impact of platelet inhibitors, specifically clopidogrel and aspirin, on clot kinetics, strength, and/or structure during the use of thrombin based gelatin matrices and fibrin sealants.

Methods: Blood was collected and heparinized from donors on clopidogrel (and aspirin) and age matched control donors.

Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use.

Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models.

Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat.

Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring. Preliminary genome-wide analyses of gene transcription and DNA methylation of the molecular basis for such maternal effects suggested differences in the epigenetic state and transcriptional activity of the Grm1 gene in the rat as a function of maternal care. Grm1 encodes the type I metabotropic glutamate receptor (mGluR1), and we found increased mGluR1 mRNA and protein in hippocampus from the adult offspring of mothers showing an increased frequency of pup licking/grooming (i.

Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone-serotonin-NGFI-A signalling cascade.

Variations in parental care direct phenotypic development across many species. Variations in maternal pup licking/grooming (LG) in the rat regulate the development of individual differences in hypothalamic-pituitary-adrenal responses to stress. The adult offspring of mothers that show an increased frequency of pup LG have increased hippocampal glucocorticoid receptor (GR) expression and more modest pituitary-adrenal responses to stress.

Environmental regulation of the neural epigenome.

Parental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands.

Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus.

Parenting and the early environment influence the risk for various psychopathologies. Studies in the rat suggest that variations in maternal care stably influence DNA methylation, gene expression, and neural function in the offspring. Maternal care affects neural development, including the GABAergic system, the function of which is linked to the pathophysiology of diseases including schizophrenia and depression.