Data-driven analysis identifies novel modulation of social behavior in female mice witnessing chronic social defeat stress.

Background: Chronic social defeat stress is a widely used depression model in male mice. Several proposed adaptations extend this model to females with variable, often marginal effects. We examine if the widely used male-defined metrics of stress are suboptimal in females witnessing defeat.

Early-life stress alters chromatin modifications in VTA to prime stress sensitivity.

Early-life stress increases sensitivity to subsequent stress, which has been observed among humans, other animals, at the level of cellular activity, and at the level of gene expression. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin.

Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior.

Proper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development.

Transcriptional signatures of early-life stress and antidepressant treatment efficacy.

Individuals with a history of early-life stress (ELS) tend to have an altered course of depression and lower treatment response rates. Research suggests that ELS alters brain development, but the molecular changes in the brain following ELS that may mediate altered antidepressant response have not been systematically studied. Sex and gender also impact the risk of depression and treatment response.

Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior.

Proper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development.

Overlapping representations of food and social stimuli in mouse VTA dopamine neurons.

Dopamine neurons of the ventral tegmental area (VTA) respond to food and social stimuli and contribute to both forms of motivation. However, it is unclear whether the same or different VTA neurons encode these different stimuli. To address this question, we performed two-photon calcium imaging in mice presented with food and conspecifics and found statistically significant overlap in the populations responsive to both stimuli.

Overlapping representations of food and social stimuli in VTA dopamine neurons.

Dopamine neurons of the ventral tegmental area (VTA ) respond to food and social stimuli and contribute to both forms of motivation. However, it is unclear if the same or different VTA neurons encode these different stimuli. To address this question, we performed 2-photon calcium imaging in mice presented with food and conspecifics, and found statistically significant overlap in the populations responsive to both stimuli.

Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.

The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal in mice with peripheral nerve injury.

African striped mice (Rhabdomys pumilio) as a neurobehavioral model for male parental care.

Parental care is diversely demonstrated across the animal kingdom, such that active practitioners and repertoires of parental behavior vary dramatically between and within taxa. For mammals, maternal care is ubiquitous while paternal and alloparental care are rare. The African striped mouse, a rodent species in the family Muridae, demonstrates maternal, paternal, and alloparental care.

Neuropathic pain as a trigger for histone modifications in limbic circuitry.

Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit lasting gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications involved with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray (PAG), lateral hypothalamus (LH), nucleus accumbens (NAc), and ventral tegmental area (VTA) 5 weeks after sciatic nerve injury in mice to model chronic pain.

Crystallin Mu in Medial Amygdala Mediates the Effect of Social Experience on Cocaine Seeking in Males but Not in Females.

Background: Social experiences influence susceptibility to substance use disorder. The adolescent period is associated with the development of social reward and is exceptionally sensitive to disruptions to reward-associated behaviors by social experiences. Social isolation (SI) during adolescence alters anxiety- and reward-related behaviors in adult males, but little is known about females.

Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior.

Background: Major depressive disorder is one of the most commonly diagnosed mental illnesses worldwide, with a higher prevalence in women than in men. Although currently available pharmacological therapeutics help many individuals, they are not effective for most. Animal models have been important for the discovery of molecular alterations in stress and depression, but difficulties in adapting animal models of depression for females has impeded progress in developing novel therapeutic treatments that may be more efficacious for women.

Trauma exposure and mental health outcomes among Central American and Mexican children held in immigration detention at the United States-Mexico border.

We explored the associations between early-life adversity and migration-related stress on the mental health of Central American and Mexican migrating children held in United States immigration detention facilities. Migrating children have high rates of trauma exposure prior to and during migration. Early-life adversity increases risk for developing mental health disorders.

Impact of Early Life Stress on Reward Circuit Function and Regulation.

Early life stress - including experience of child maltreatment, neglect, separation from or loss of a parent, and other forms of adversity - increases lifetime risk of mood, anxiety, and substance use disorders. A major component of this risk may be early life stress-induced alterations in motivation and reward processing, mediated by changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here, we review evidence of the impact of early life stress on reward circuit structure and function from human and animal models, with a focus on the NAc.

Chronic Intermittent Hypoxia Enhances Pathological Tau Seeding, Propagation, and Accumulation and Exacerbates Alzheimer-like Memory and Synaptic Plasticity Deficits and Molecular Signatures.

Background: Obstructive sleep apnea, characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), is a risk factor for Alzheimer's disease (AD) progression. Recent epidemiological studies point to CIH as the best predictor of developing cognitive decline and AD in older adults with obstructive sleep apnea. However, the precise underlying mechanisms remain unknown.

Sperm Transcriptional State Associated with Paternal Transmission of Stress Phenotypes.

Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation.

Sex-Specific Role for SLIT1 in Regulating Stress Susceptibility.

Background: Major depressive disorder is a pervasive and debilitating syndrome characterized by mood disturbances, anhedonia, and alterations in cognition. While the prevalence of major depressive disorder is twice as high for women as men, little is known about the molecular mechanisms that drive sex differences in depression susceptibility.

Methods: We discovered that SLIT1, a secreted protein essential for axonal navigation and molecular guidance during development, is downregulated in the adult ventromedial prefrontal cortex (vmPFC) of women with depression compared with healthy control subjects, but not in men with depression.

Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons.

Animals susceptible to chronic social defeat stress (CSDS) exhibit depression-related behaviors, with aberrant transcription across several limbic brain regions, most notably in the nucleus accumbens (NAc). Early life stress (ELS) promotes susceptibility to CSDS in adulthood, but associated enduring changes in transcriptional control mechanisms in the NAc have not yet been investigated. In this study, we examined long-lasting changes to histone modifications in the NAc of male and female mice exposed to ELS.

Genome-wide Signatures of Early-Life Stress: Influence of Sex.

Both history of early-life stress (ELS) and female sex are associated with increased risk for depression. The complexity of how ELS interacts with brain development and sex to impart risk for multifaceted neuropsychiatric disorders is also unlikely to be understood by examining changes in single genes. Here, we review an emerging literature on genome-wide transcriptional and epigenetic signatures of ELS and the potential moderating influence of sex.

Determination of the Fluoride Content in Water of Aqueducts of Cauca (Colombia) by Ion Exchange Chromatography.

Water for human consumption is the main source of fluoride exposure. The concentration in water should not exceed 1 mg/L of fluoride since, at higher levels; it increases the risk of dental fluorosis, among other adverse effects. The fluoride content of 149 water samples from different aqueducts in Cauca (Colombia) has been determined by ion exchange chromatography with the aim of fluoride risk assessment.

Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum.

Major depressive disorder (MDD) is a complex condition with unclear pathophysiology. Molecular disruptions within limbic brain regions and the periphery contribute to depression symptomatology and a more complete understanding the diversity of molecular changes that occur in these tissues may guide the development of more efficacious antidepressant treatments. Here, we utilized a mouse chronic social stress model for the study of MDD and performed metabolomic, lipidomic, and proteomic profiling on serum plus several brain regions (ventral hippocampus, nucleus accumbens, and medial prefrontal cortex) of susceptible, resilient, and unstressed control mice.

Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression.

Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males.