Adolescent Offspring Research Articles

Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity

Maternal obesity has been recognized as a stressor affecting the developing fetal brain, leading to long-term negative outcomes comparable to those resulting from maternal psychological stress, although the mechanisms have not been completely elucidated. In this study, we tested the hypothesis that adverse prenatal conditions as diverse as maternal stress and maternal obesity might affect emotional regulation and stress response in the offspring through common pathways, with a main focus on oxidative stress and neuroplasticity. We contrasted and compared adolescent male and female offspring in two mouse models of maternal psychophysical stress (restraint during pregnancy - PNS) and maternal obesity (high-fat diet before and during gestation - mHFD) by combining behavioral assays, evaluation of the hypothalamic–pituitary–adrenal (HPA) axis reactivity, immunohistochemistry and gene expression analysis of selected markers of neuronal function and neuroinflammation in the hippocampus, a key region involved in stress appraisal. Prenatal administration of the antioxidant N-acetyl-cysteine (NAC) was used as a strategy to protect fetal neurodevelopment from the negative effects of PNS and mHFD. Our findings show that these two stressors produce overlapping effects, reducing brain anti-oxidant defenses (Nrf-2) and leading to sex-dependent impairments of hippocampal Bdnf expression and alterations of the emotional behavior and HPA axis functionality. Prenatal NAC administration, by restoring the redox balance, was able to exert long-term protective effects on brain development, suggesting that the modulation of redox pathways might be an effective strategy to target common shared mechanisms between different adverse prenatal conditions.

Association Between Parental BMI and Offspring's Blood Pressure by Mediation Analysis: A Study Using Data From the Korean National Health and Nutrition Examination Survey.

This study analyzed the relationship between parental body mass index (BMI; BMI_p) and hypertension in their adolescent offspring (HTN_a), focusing on the mediating effect of adolescents' BMI (BMI_a). Utilizing data from the Korea National Health and Nutrition Examination Survey, including participants aged 12-18, we conducted a mediation analysis while controlling for confounding factors such as age, sex, physical activity, dietary habits, household income quartile, and parents' alcohol and smoking habits. The study included a total of 5731 participants, of whom 3381 and 5455 participants had data on fathers' and mothers' BMI, respectively. For adolescent systolic blood pressure (SBP_a), the father's BMI (BMI_f) had a significant total effect (β, 0.23; 95% confidence interval [CI], 0.12 to 0.34) and average controlled mediated effect (ACME) (β, 0.27; 95% CI, 0.23 to 0.32), but the average direct effect (ADE) was not significant. The mother's BMI (BMI_m) had a significant total effect (β, 0.17; 95% CI, 0.09 to 0.25), ACME (β, 0.25; 95% CI, 0.22 to 0.28) and ADE (β, -0.08; 95% CI, -0.16 to 0.00). For adolescent diastolic blood pressure, both BMI_f and BMI_m had significant ACMEs (β, 0.10; 95% CI, 0.08 to 0.12 and β, 0.09; 95% CI, 0.07 to 0.12, respectively), BMI_m had a significant ADE (β, -0.09; 95% CI, -0.16 to -0.02) but BMI_f had an insignificant ADE and total effect. The study found that parental BMI had a significant effect on SBP_a, mediated through BMI_a. Therefore, a high BMI in parents could be a risk factor, mediated through BMI_a, for systolic hypertension in adolescents, necessitating appropriate management.

Vulnerability and resilience to prenatal stress exposure: behavioral and molecular characterization in adolescent rats

Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others appear to be resilient. In this study, we aimed to characterize the effects of prenatal stress (PNS) exposure in rats at adolescence and to identify subgroup of animals with a differential response to the gestational manipulation. PNS adolescent offspring (regardless of sex) showed impaired emotionality in different pathological domains, such as anhedonia, anxiety, and sociability. However, using cluster analysis of the behavioral data we could identify 70% of PNS-exposed animals as vulnerable (PNS-vul), whereas the remaining 30% were considered resilient (PNS-res). At the molecular level, we found that PNS-res males show a reduced basal activation of the ventral hippocampus whereas other regions, such as amygdala and dorsal hippocampus, show significant PNS-induced changes regardless from vulnerability or resilience. Taken together, our results provide evidence of the variability in the behavioral and neurobiological effects of PNS-exposed offspring at adolescence. While these data may advance our understanding of the association between exposure to stress during gestation and the risk for psychopathology, the investigation of the mechanisms associated to stress vulnerability or resilience may be instrumental to develop novel strategies for therapeutic intervention.

Perinatal morphine but not buprenorphine affects gestational and offspring neurobehavioral outcomes in mice

Within the national opioid epidemic, there has been an increase in the number of infants exposed to opioids in utero. Additionally, opioid agonist medications are the standard of care for women with opioid use disorder during pregnancy. Buprenorphine (BUP), a partial µ -opioid receptor agonist, has been successful in improving gestational and neonatal outcomes. However, in utero exposure has been linked to childhood cognitive and behavioral problems. Therefore, we sought to compare offspring cognitive and behavioral outcomes after prenatal exposure to a clinically relevant low dose of BUP compared to morphine (MO), a full µ -opioid receptor agonist and immediate metabolite of heroin. We used a mouse model to assess gestational and offspring outcomes. Mouse dams were injected once daily s.c. with saline (SAL, n = 12), MO (10 mg/kg, n = 15), or BUP (0.1 mg/kg, n = 16) throughout pre-gestation, gestation, and lactation until offspring were weaned on postnatal day (P)21. Offspring social interaction and exploratory behavior were assessed, along with executive function via the touchscreen 5 choice serial reaction time task (5CSRTT). We then quantified P1 brain gene expression in the frontal cortex and amygdala (AMG). Perinatal MO but not BUP exposure decreased gestational weight gain and was associated with dystocia. In adolescent offspring, perinatal MO but not BUP exposure increased social exploration in males and grooming behavior in females. In the 5CSRTT, male MO exposed offspring exhibited increased impulsive action errors compared to male BUP offspring. In the AMG of P1 MO exposed offspring, we observed an increase in gene expression of targets related to activity of microglia. Importantly, both MO and BUP caused acute hyperlocomotion in the dams to a similar degree, indicating that the selected doses are comparable, in accordance with previous dose comparisons on analgesic and reward efficacy. These data suggest that compared to MO, low dose BUP improves gestational outcomes and has less of an effect on the neonatal offspring brain and later adolescent and adult behavior.

Maternal aggressive behavior in interactions with adolescent offspring: Proximal social-cognitive predictors in depressed and nondepressed mothers.

Maternal depressive symptoms are associated with elevations in harsh parenting behavior, including criticism, negative affect, and hostile or coercive behavior, and these behaviors contribute to associations between maternal depressive symptomatology and child functioning. We used multilevel survival analysis to examine social-cognitive processes as proximal predictors of the onset and offset of maternal aggressive behavior during interactions with their adolescent children. Low-income women (N = 180) were selected for either: (a) elevated depressive symptoms and a history of treatment for depression (depressed group) or (b) not more than mild levels of current depressive symptomatology, no history of depression treatment, and no current mental health treatment (nondepressed group). These women and their adolescent children (ages 11-14, M = 12.93; 96 male sex, as assigned at birth) participated in a dyadic problem-solving interaction and mothers completed a video-mediated recall procedure, in which they watched a segment of the interaction, labeled their adolescents' affect, and made attributions for their behavior. Mothers in the depressed group were more likely to initiate aggressive behavior and, once initiated, were less likely to transition out of it. Mothers in both groups were less likely to transition out of aggressive behavior when they made negative attributions for their adolescents' behavior. Findings point to promising cognitive and behavioral targets for intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Parent-Perceived Benefits and Harms Associated With Internet Use by Adolescent Offspring

Limited systematic information on familial factors and perception of the benefits and harms of internet use by youths is available. Much of the current research has been hampered by small nondiverse samples and limited information on key familial and offspring characteristics. To characterize parental perceptions and concerns about internet use associated with adolescent development, well-being, safety, family connectedness, and potential for problematic internet use. A 20-minute, English-language survey was developed with expert stakeholders using previously validated questionnaires and was conducted online between June 17 and July 5, 2022. Participants included 1005 parents of children and adolescents aged 9 to 15 years drawn from an online digital survey platform and calibrated for representation with post hoc weightings. Parent survey responses about family characteristics and internet use were used to compute Internet Addiction Test scores for parents and their offspring, Alabama Parenting Questionnaire scores, and an aggregate family connectedness score. The survey cohort of 1005 parents included 568 women (56.5%) and 437 men (43.5%) with a mean age (SD) of 39.5 (6.4) years. In terms of race and ethnicity, the most common categories included Black or African American (95 [9.5%]), Latinx or Hispanic (100 [10.0%]), White (602 [59.9%]), and 2 or more races or ethnicities (122 [12.1%]). Respondents endorsed parental concerns that included exposure to harmful content (646 [64.3%]) and online bullying (533 [53.0%]). Two hundred twenty-five parents (22.4%) had specific concerns about internet addiction in their adolescent offspring, and twice as many parents reported specific concerns about internet addiction than substance addiction. However, parents also indicated that internet use improved family connectedness among immediate families (468 [46.6%]) and extended families (568 [56.5%]). Internet Addiction Test scores in adolescent offspring were correlated with parent scores (β = 0.62 [SE = 0.02]; P < .001) and Alabama Parenting Questionnaire-Inconsistent Discipline scores (β = 0.23 [SE = 0.11]; P = .04). In this survey study of parent perceptions of internet use among adolescent offspring, parents believed the internet brought families closer yet also expressed concerns. Problematic internet use among youths was correlated with negative parenting styles and parent internet use. This research adds to the literature by suggesting that families, their communities, and industry may have common ground to collaborate on reducing the negative effects of internet use.

Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity.

Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.

Long-term effects of prenatal infection on the human brain: a prospective multimodal neuroimaging study

There is convincing evidence from rodent studies suggesting that prenatal infections affect the offspring’s brain, but evidence in humans is limited. Here, we assessed the occurrence of common infections during each trimester of pregnancy and examined associations with brain outcomes in adolescent offspring. Our study was embedded in the Generation R Study, a large-scale sociodemographically diverse prospective birth cohort. We included 1094 mother-child dyads and investigated brain morphology (structural MRI), white matter microstructure (DTI), and functional connectivity (functional MRI), as outcomes at the age of 14. We focused on both global and focal regions. To define prenatal infections, we composed a score based on the number and type of infections during each trimester of pregnancy. Models were adjusted for several confounders. We found that prenatal infection was negatively associated with cerebral white matter volume (B = −0.069, 95% CI −0.123 to −0.015, p = 0.011), and we found an association between higher prenatal infection scores and smaller volumes of several frontotemporal regions of the brain. After multiple testing correction, we only observed an association between prenatal infections and the caudal anterior cingulate volume (B = −0.104, 95% CI −0.164 to −0.045, p < 0.001). We did not observe effects of prenatal infection on other measures of adolescent brain morphology, white matter microstructure, or functional connectivity, which is reassuring. Our results show potential regions of interest in the brain for future studies; data on the effect of severe prenatal infections on the offspring’s brain in humans are needed.

Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance

Maternal stress (MS) during gestation is known to increase the risk for the development of behavioural and physiological disorders and advances cellular aging. In this study, we investigated whether the supplementation of standardized Bacopa monnieri extract (CDRI-08/BME) or l-Carnosine (L-C) to the mother exposed to social stress during gestation modify the effect on their offspring's neurobehaviour, antioxidant defence gene expression, telomere length, and telomere biology. To test this, timed pregnant rats were subjected to social stress during the gestational day (GD) 16–18. A subset of stressed pregnant rats received either BME [80 mg/kg in 0.5% gum acacia (per-orally; p.o)] or L-C [1 mg/kg (p.o)] every day from GD-10 to until their pup's attained postnatal day (PND)-23. We observed that MS induced anxiety-like behaviour, altered inter-limb coordination, antioxidant defence genes [Superoxide dismutase (SOD1,2), Catalase (CAT), Glutathione peroxidase-3 (GPX3)], telomerase reverse transcriptase (TERT), shelterin complex subunits (TRF1, RAP1B, POT1) protein level and shorten telomere length. Notably, supplementation of BME/L-C dampens the MS, thus the effect on neurobehaviour, antioxidant defence gene expression, and telomere biology is minimized in their offspring. Together, our results suggest that supplementation of BME/L-C during gestation dampens the MS and reduced oxidative stress-mediated changes in telomere shortening/biology and associated neurobehaviour in offspring born following MS.

A Maternal Western-Style Diet Impairs Skeletal Muscle Lipid Metabolism in Adolescent Japanese Macaques.

In lean, active adolescent offspring, a postweaning Western-style diet (pwWD) leads to shifts in body fat distribution that are associated with poorer insulin sensitivity. Fatty acid-linked oxidative metabolism was reduced in skeletal muscles from offspring exposed to maternal Western-style diet (mWD) even when weaned to a healthy control diet for years. Reduced oxidative phosphorylation complex I-V and VDAC1 abundance partially explain decreased skeletal muscle respiration in mWD offspring. Prior exposure to mWD results in greater fold increase with pwWD in saturated lipids and bioactive lipid molecules (i.e. ceramide and sphingomyelin) associated with insulin resistance.

Parental Dieting and Correlation with Disordered Eating Behaviours in Adolescents: A Narrative Review

Adolescent eating disorders and disordered eating behaviours appear to be a growing public health concern. The aetiology of these conditions is complex, as many different factors contribute to their development. Among them, family factors such as parenting styles and comments regarding weight coming from family members are considered critical and are extensively researched. However, the impact of parental dieting has received less attention. A literature review was conducted in order to examine the relationship between parental engagement in weight-reduction dieting and their adolescent offspring’s disordered eating behaviours. The review was conducted in three databases (PubMed, Scopus and Google Scholar) regarding the period between January 2000 and May 2023. The initial search retrieved 339 abstracts, and 113 full reports were evaluated for eligibility. Six studies fulfilled the inclusion criteria and were included in the final literature review. A number of studies indicated that adolescents whose parents were engaged in dieting in order to lose weight are more likely to showcase disordered eating behaviours. However, research regarding this relationship is very scarce. More studies on the link between parental eating and dieting habits and the risk of disordered eating in adolescents are required. Moreover, parents should be informed regarding the possible risks when they choose to follow weight-loss diets and the importance of adopting healthy eating and weight-control habits for the whole family.

Postpartum scarcity-adversity inflicts sex-specific cerebellar adaptations and reward behaviors in adolescence

Early life adversity in the form of poor postnatal care is a major developmental stressor impacting behavior later in life. Previous studies have shown the impact of early life stress on neurobehavioral abnormalities. Specifically, research has demonstrated how limited bedding and nesting (LBN) materials can cause behavioral deficits in adulthood. There is, however, a limited understanding of how LBN influences sex-specific neurobehavioral adaptation in adolescence, a developmental stage susceptible to psychiatric diseases including substance use disorder. LBN and stress-naive c57BL/6 adolescent male and female mouse offspring were tested for a battery of behaviors including open field, novel object recognition, elevated plus maze, social preference, and morphine-induced conditioned place preference. There was a significant sex-specific deficit in social preference in male mice exposed to LBN compared to stress-naïve counterparts and both LBN males and females had a higher preference towards the drug-paired chamber in the morphine-induced conditioned place preference test. These behavioral deficits were concomitant with sex-specific increases in the transcription factor, Klf9 in the deep cerebellar nuclei (DCN) of males. Further, mRNA levels of the circadian gene Bmal1, which is known to be transcriptionally regulated by Klf9, were decreased in the DCN. Since Bmal1 has recently been implicated in extracellular matrix modulation, we examined perineuronal nets (PNN) and observed depleted PNN in the DCN of males but not female LBN mice. Overall, we provide a novel understanding of how postpartum adversity impinges on the cerebellar extracellular matrix homeostasis, likely, through disruption of the circadian axis by Klf9 that might underlie sex-specific behavioral adaptations in adolescence.

The development of co-designed parent-supported cognitive behaviour therapy for perfectionism in adolescents with eating disorders: initial feasibility and acceptability

BackgroundPerfectionism is significantly associated with symptoms of eating disorders in adolescents. Studies to date have not examined parent-supported CBT for perfectionism in eating disorders (CBT-P-ED). We co-designed the treatment and conducted a feasibility trial.MethodsEight parents of adolescents with eating disorders (M age = 48.75 years, 100% female) engaged in three co-design workshops to create a parent-supported CBT-P-ED self-help intervention. A further 10 parents (M age 41.8 years, 50% female) and their adolescent offspring (n = 10, M age 15.4 years, 60% female, 50% with self-reported diagnosis of anorexia nervosa) participated in a feasibility trial and provided feedback on the intervention.ResultsThe parents who engaged in the co-design workshops suggested several areas to optimise the perfectionism intervention, including using plain language, the impact of parental perfectionism, how to engage with their adolescent in treatment and the importance of increasing eating disorder specific material. Feedback from the feasibility trial suggested that the intervention was acceptable and feasible with 100% of parents and adolescents saying it was useful, and no attrition.ConclusionsParent-supported CBT-P-ED appears to be feasible. Future research is now required in a randomised controlled trial.

Impaired erythropoietin-producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats.

An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin-producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre-pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho-cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.

Impact of Parental Mental Health and Help-Seeking on Adolescents' Suicidal Ideations and Help-Seeking Behaviors.

This study aimed to evaluate the impact of parental mental health on adolescent offspring. Data regarding 6512 families from the 2010-2021 Korean National Health and Nutrition Examination Survey were analyzed; among them, 428 were placed in the suicidal ideation (SI) group and 421 were placed in the matched control (MC) group. This number was selected for the use of the propensity score matching method. The findings highlighted significant associations between parental mental health and adolescent suicidal ideation, with mothers in the SI group having higher odds of Diagnosed Depression (OR 2.109, 1.023-4.350 95% CI), Depressive Mood (OR 2.155, 1.224-3.793 95% CI), and Suicidal Ideation (OR 2.532, 1.322-4.851 95% CI) compared to the MC group. Regarding the fathers, paternal Suicidal Ideation (OR 4.295, 1.747-10.599 95% CI) was the only significant factor for adolescent suicidal ideation. In contrast, maternal depressive symptoms and help-seeking behavior significantly impacted adolescent help-seeking; Maternal Depressive Mood increased with adolescent Help-Seeking (OR 4.486, 1.312-15.340 95% CI) while Maternal Suicidal Ideation reduced the probability of Help-Seeking in the SI group (OR 0.15, 0.031-0.721, 95% CI). Chronic and severe depressive symptoms in mothers could make adolescents less likely to seek help for their suicidal ideations. Therefore, clinicians working with adolescents should prioritize a family-oriented approach.

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity.

Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for "brain reprogramming", we aimed at assessing the role of the non-psychoactive phytocannabinoid cannabidiol (CBD) as a rescue strategy to temper prenatal THC-induced harm. Methods: To this aim, Wistar rats prenatally exposed to THC (2mg/kg s.c.) or vehicle (gestational days 5-20) were tested for specific indexes of spatial and configural memory in the reinforcement-motivated Can test and in the aversion-driven Barnes maze test during adolescence. Markers of hippocampal excitatory plasticity and endocannabinoid signaling-NMDAR subunits NR1 and 2A-, mGluR5-, and their respective scaffold proteins PSD95- and Homer 1-; CB1R- and the neuromodulatory protein HINT1 mRNA levels were evaluated. CBD (40mg/kg i.p.) was administered to the adolescent offspring before the cognitive tasks. Results: The present results show that prenatal THC impairs hippocampal memory functions and the underlying synaptic plasticity; CBD is able to mitigate cognitive impairment in both reinforcement- and aversion-related tasks and the neuroadaptation of hippocampal excitatory synapses and CB1R-related signaling. Discussion: While this research shows CBD potential in dampening prenatal THC-induced consequences, we point out the urgency to curb cannabis use during pregnancy in order to avoid detrimental bio-behavioral outcomes in the offspring.

Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders.

Recent data suggest that defects in purinergic signalling are a common denominator of autism spectrum disorders (ASDs), though nothing is known about whether the disorder-related imbalance occurs at the receptor level. In this study, we investigated whether prenatal exposure to valproic acid (VPA) induces changes in purinergic receptor expression in adolescence and whether it corresponds to glial cell activation. Pregnant dams were subjected to an intraperitoneal injection of VPA at embryonic day 12.5. In the hippocampi of adolescent male VPA offspring, we observed an increase in the level of P2X1, with concomitant decreases in P2X7 and P2Y1 receptors. In contrast, in the cortex, the level of P2X1 was significantly reduced. Also, significant increases in cortical P2Y1 and P2Y12 receptors were detected. Additionally, we observed profound alterations in microglial cell numbers and morphology in the cortex of VPA animals, leading to the elevation of pro-inflammatory cytokine expression. The changes in glial cells were partially reduced via a single administration of a non-selective P2 receptor antagonist. These studies show the involvement of purinergic signalling imbalance in the modulation of brain inflammatory response induced via prenatal VPA exposure and may indicate that purinergic receptors are a novel target for pharmacological intervention in ASDs.

Parental drinking, mental health and educational level, and offspring’s subsequent prescription drugs treatment for sleep problems. A longitudinal HUNT survey and registry study

BackgroundParental drinking, mental health and family socioeconomic status are all associated with offspring sleep problems, but there is a paucity of research that considers the effect of risk factors, as they co-occur within and across families. Also, sleep problems are closely linked with mental health problems. Disentangling the effects on one or the other are important. We examined whether parental risk constellations are differently associated with offspring’s subsequent prescription drug use for sleep problems during nine years with or without prescription drug use for anxiety and/or depression.MethodsThe sample included 8773 adolescent offspring of 6696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway. The exposures were five parental risk constellations, previously identified via Latent Profile Analysis, characterized by drinking frequencies and quantities, mental health, and years of education. The outcomes were dispensed prescription drugs in offspring during 2008–2016 for (a) only sleep problems (b) sleep problems and anxiety/depression or (c) only anxiety/depression. We used multinomial logistic regression to model the odds of the outcomes.ResultsCompared to the overall low-risk parental constellation, none of the risky constellations were significantly associated with increased risk of being dispensed prescription drugs only for sleep problems. Offspring from two different risk profiles were at increased risk for being dispensed both sleep and anxiety/depression prescription drugs. These were parental profiles marked by (1) low education, symptoms of mental health problems and weekly binge drinking in both parents (OR 1.90, CI = 1.06;3.42); and (2) frequent heavy drinking in both parents and symptoms of mental health problems in fathers (OR 3.32, CI = 1.49;7.39). Offspring from the risk profile with lowest parental education had increased risk of only anxiety/depression prescription drugs (OR 1.25, CI = 1.05;1.49).ConclusionOur findings suggest that parental risk constellations are not associated with increased risk of offspring receiving sleep medications without also receiving anxiety/depression medications, as two risk constellations were associated with increased risk of dispensation of both sleep and anxiety/depression prescription drugs. Receiving both may be an indication of severity. The findings underscore the importance of including measures of mental health problems when investigating sleep problems to avoid misattribution of effects.

The effects of forced exercise and zinc supplementation during pregnancy on prenatally stress-induced behavioral and neurobiological consequences in adolescent female rat offspring.

Prenatal manipulations can lead to neurobehavioral changes in the offspring. In this study, individual and combined effects of forced exercise and zinc supplementation during pregnancy on prenatally restraint stress (PRS)-induced behavioral impairments, neuro-inflammatory responses, and oxidative stress have been investigated in adolescent female rat offspring. Pregnant rats were divided into five groups: control; restraint stress (RS); RS+exercise stress (RS+ES), RS+zinc supplementation (RS+Zn); and RS+ES+Zn. All the pregnant rats (except control) were exposed to RS from gestational days 15 to 19. Pregnant rats in ES groups were subjected to forced treadmill exercise (30min/daily), and in Zn groups to zinc sulfate (30mg/kg/orally), throughout the pregnancy. At postnatal days 25-27, anxiety-like and stress-coping behaviors were recorded, and the gene expressions of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and the concentration of total antioxidant capacity were measured in the prefrontal cortex. PRS significantly enhanced anxiety, generated passive coping behaviors, increased IL-1β and TNF-α expression, and decreased the antioxidant capacity. ES potentiated while zinc reversed PRS-induced behavioral impairments. Prenatal zinc also restored the anti-inflammatory and antioxidant capacity but had no effect on additive responses imposed by the combination of RS and ES. Suppression of PRS-induced behavioral and neurobiological impairments by zinc suggests the probable clinical importance of zinc on PRS-induced changes on child temperament.

Chronic maternal morphine exposure and early-life adversity induce impairment in synaptic plasticity of adolescent male rats

Maternal morphine exposure has negative consequences for learning and memory in the offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal Separation (MS) can cause behavioral and neuropsychiatric problems later in life. It seems that adolescents are more susceptible to the effects of early life stress; evidence for the combinatory effects of oral chronic maternal morphine exposure and MS in the CA1 area of the hippocampus in the male adolescent offspring is not found. Therefore, this study aimed to evaluate the effects of chronic maternal morphine consumption (21 days before and after mating, and gestation), and MS (180 min/day from postnatal day (PND) 1–21) on the synaptic plasticity of male offspring in mid-adolescence. Control, MS, Vehicle (V), Morphine, V + MS, and Morphine + MS groups were tested for in vivo field potential recording from the CA1 area of the hippocampus. The current results demonstrated that chronic maternal morphine exposure impaired the induction of early long-term potentiation (LTP). MS impaired average fEPSPs, induction of early-LTP and maintenance. Chronic maternal morphine exposure in combination with MS impaired the induction of early LTP but didn't deteriorate maintenance and the average field excitatory post-synaptic potentials (fEPSPs) measured in two hours. Prepulse facilitation ratios remained undisturbed and I/O curves showed decreased fEPSP slopes at high stimulus intensities in combinatory group. We concluded that chronic maternal morphine exposure in combination with MS negatively affects synaptic plasticity in the CA1 area in male adolescent offspring.