Preconception parental predator stress induces brain and behavioral changes in offspring

Brain and behaviour are shaped by experience. Recent data suggest that experiences of the parents can be ‘passed-on’ to alter brain and behavior of future generations. Stress during the preconception period is a new topic of interest, as it involves both prospective parents. The current study examined how parental preconception predator stress impacts the development of offspring brain and behaviour throughout its lifespan. Male and female mice (F0) were exposed to a live rat (rat exposure test) or control condition (no live rat exposure) for five minutes. Two days later, all mice underwent the elevated plus maze to assess anxiety-like behavior. Eight days later (a total of 10 days post predator exposure), stressed males were mated to stressed females and control males were mated to control females. Behavior of the offspring (F1) was assessed during adolescence and again in adulthood (following a mild stressor). F0 and F1 brains were examined for stress-induced changes in glucocorticoid receptors (GR), FK506 binding protein 5 (FKBP5), doublecortin, and c-FOS. Following a mild stressor, preconception stressed offspring show increased anxiety-like behavior, hyperarousal, and deficits in spatial memory. These mice also show elevated plasma corticosterone and altered GR, FKBP5 and c-FOS expression in the hippocampus. Furthermore, following a mild stressor, offspring (F2 generation) with at least one set of grandparents who were predator stressed showed increased anxiety-like behavior, enhanced hyperarousal, and deficits in spatial memory compared to offspring whose both sets of grandparents were controls. Despite the high incidence and potentially tragic outcome, there is little research on neural mechanisms underlying stress-induced disorders such as posttraumatic stress disorder (PTSD). These results may contribute to identifying at-risk individuals, as well as point to potential novel therapies for these devastating disorders

Pancreatic Cancer Early Detection trough Hyperpolarized MRI

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Stress Across Generations: DNA Methylation as a Potential Mechanism Underlying Intergenerational Effects of Stress in Both Post-traumatic Stress Disorder and Pre-clinical Predator Stress Rodent Models

Although most humans will experience some type of traumatic event in their lifetime only a small set of individuals will go on to develop post-traumatic stress disorder (PTSD). Differences in sex, age, trauma type, and comorbidity, along with many other elements, contribute to the heterogenous manifestation of this disorder. Nonetheless, aberrant hypothalamus-pituitary-adrenal (HPA) axis activity, especially in terms of cortisol and glucocorticoid receptor (GR) alterations, has been postulated as a tenable factor in the etiology and pathophysiology of PTSD. Moreover, emerging data suggests that the harmful effects of traumatic stress to the HPA axis in PTSD can also propagate into future generations, making offspring more prone to psychopathologies. Predator stress models provide an ethical and ethologically relevant way to investigate tentative mechanisms that are thought to underlie this phenomenon. In this review article, we discuss findings from human and laboratory predator stress studies that suggest changes to DNA methylation germane to GRs may underlie the generational effects of trauma transmission. Understanding mechanisms that promote stress-induced psychopathology will represent a major advance in the field and may lead to novel treatments for such devastating, and often treatment-resistant trauma and stress-disorders

A histone deacetylase inhibitor, trichostatin-A, induces odor preference memory extension and maintains enhanced AMPA receptor expression in the rat pup model

Histone deacetylase (HDAC) plays a role in synaptic plasticity and long-term memory formation. I hypothesized that trichostatin-A (TSA), an HDAC inhibitor, would promote long-term odor preference memory and maintain enhanced GluA1 receptor levels that might support memory. I used an early odor preference learning model in neonate rat pups to test behavior and examine receptor protein expression. My behavioral studies showed that intrabulbar infusion of TSA, prior to pairing of the conditioned stimulus (peppermint odor) with the unconditioned stimulus (tactile stimulation), prolonged odor preference memory for at least nine days. Western blot analysis showed that GluA1 receptor membrane expression in the olfactory bulbs of TSA-treated pups was significantly increased at 48 h. Immunohistochemistry revealed significant increase of GluA1 expression in olfactory bulb glomeruli five days after training. These results support evidence for a relationship between enhanced GluA1 receptor expression and memory. These findings will permit further exploration of mechanisms which induce and maintain memories

Neonatal opioid withdrawal syndrome and implications for pain assessment in the newborn: a scoping review

Background: During the last decade, an increase in maternal opioid use has resulted in newborns requiring management for withdrawal. Typical symptoms of neonatal opioid withdrawal syndrome [NOWS] are difficult to distinguish from pain behaviors, and management measures involve both distress/pain assessment as well as management by healthcare personnel. Both factors are independently known to have an adverse impact on neurodevelopmental pathways in neonates with NOWS. This scoping review aimed to explore the literature available regarding NOWS and its implications for pain assessment. Methods: This scoping review has been conducted in accordance with the Joanna Briggs Institute [JBI] methodology. A comprehensive search strategy using 5 databases was employed. Two reviewers assessed full-text articles based on predefined criteria. Results: The initial literature search resulted in a total of 4794 articles of which 7 articles were related to distress/pain in NOWS. Pain assessment measures included both subjective scoring methods and objective measures. An additional 4 preclinical studies were identified, but were not included in the results. Conclusions: Structured and targeted tools for pain scoring are needed for this population of at-risk newborns. The overlapping mechanisms of pain perception and opioid withdrawal like sympathetic stimulation make it necessary to explore objective methods to assess pain in NOWS

A short pre-conception bout of predation risk affects both children and grandchildren

Abstract Traumatic events that affect physiology and behavior in the current generation may also impact future generations. We demonstrate that an ecologically realistic degree of predation risk prior to conception causes lasting changes in the first filial (F1) and second filial (F2) generations. We exposed male and female mice to a live rat (predator stress) or control (non-predator) condition for 5 min. Ten days later, stressed males and females were bred together as were control males and females. Adult F1 offspring from preconception-stressed parents responded to a mild stressor with more anxiety-like behavior and hyperarousal than offspring from control parents. Exposing these F1 offspring to the mild stressor increased neuronal activity (cFOS) in the hippocampus and altered glucocorticoid system function peripherally (plasma corticosterone levels). Even without the mild stressor, F1 offspring from preconception-stressed parents still exhibited more anxiety-like behaviors than controls. Cross-fostering studies confirmed that preconception stress, not maternal social environment, determined offspring behavioral phenotype. The effects of preconception parental stress were also unexpectedly persistent and produced similar behavioral phenotypes in the F2 offspring. Our data illustrate that a surprisingly small amount of preconception predator stress alters the brain, physiology, and behavior of future generations. A better understanding of the ‘long shadow’ cast by fearful events is critical for understanding the adaptive costs and benefits of transgenerational plasticity. It also suggests the intriguing possibility that similar risk-induced changes are the rule rather than the exception in free-living organisms, and that such multigenerational impacts are as ubiquitous as they are cryptic

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy

Abstract Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE