Temporal dynamics of isolation calls emitted by pups in environmental and genetic mouse models of autism spectrum disorder.

Introduction: Environmental and genetic factors contribute to the increased risk for neurodevelopmental disorders, including deficits in the development of social communication. In the mouse, ultrasonic vocalizations emitted by the pup stimulate maternal retrieval and potentiate maternal care. Therefore, isolation induced ultrasonic vocalization emitted by pups provides a means to evaluate deficits in communication during early development, before other ways of communication are apparent.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment.

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate's concentration gradient from the brain to the blood and decreased levels of brain glutamate.

Essential role of the mitochondrial Na/Ca exchanger NCLX in mediating PDE2-dependent neuronal survival and learning.

Impaired phosphodiesterase (PDE) function and mitochondrial Ca (i.e., [Ca]m) lead to multiple health syndromes by an unknown pathway.

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model.

Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels.

Isolation-Induced Ultrasonic Vocalization in Environmental and Genetic Mice Models of Autism.

Studies in rodent models suggest that calls emitted by isolated pups serve as an early behavioral manifestation of communication deficits and autistic like behavior. Previous studies in our labs showed that gestational exposure to the pesticide chlorpyrifos (CPF) and the Mthfr-knock-out mice are associated with impaired social preference and restricted or repetitive behavior. To extend these studies, we examine how pup communication ultrasonic vocalizations is altered in these ASD models.

Developmental and social deficits and enhanced sensitivity to prenatal chlorpyrifos in PON1-/- mouse pups and adults.

The levels and activity of the enzyme paraoxonase 1 affect the vulnerability to the teratogenic effects of organophosphate pesticides. Mutant mice lacking the gene for paraoxonase1 (PON1-/-) are more susceptible to the toxic effects of chlorpyrifos, and were hypothesized to be more vulnerable to social behavior deficits induced by exposure to chlorpyrifos during gestation. Three experiments were performed comparing PON1-/- mice to PON1+/+ mice born to dams treated with 0.

Early life stress induces submissive behavior in adult rats.

Maternal-deprivation of rodent pups is a relevant model of extreme early-life stress that can be relevant to the understanding of long-term effects of war, migration, parental loss and displacement. Although even mild stress during infancy affects brain development and behavior, the current study focused on the effects of six hour daily maternal-separation, a model that reflects the severe distress often experienced in those circumstances. This study emphasizes the effect of maternal separation on social behavior in the context of a variety of factors that measure cognitive and emotional behavior which were subject to principle component analysis.

Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos.

Background: Signs of pervasive developmental disorder and social deficits were reported in toddlers and children whose mothers were exposed to organophosphate pesticides during pregnancy. Deficits in social preference were reported in adult male mice exposed to chlorpyrifos on gestational days 12-15. This study aimed (a) to test the hypothesis that adult female and male mice that were exposed prenatally to subtoxic doses of chlorpyrifos would be impaired in social behavior and (b) to determine if prenatal chlorpyrifos altered the expression of transcripts for oxytocin in the hypothalamus.

Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice.

Background: Children are at daily risk for exposure to organophosphate insecticides, of which the most common is chlorpyrifos (CPF). Exposure of pregnant women to CPF was linked to decreased birth weight, abnormal reflexes, reduction in IQ, as well as increased maternal reports of signs of pervasive developmental disorder. The aim of current study was to examine the long term effects of prenatal exposure to CPF in C57BL/6 J (B6) mice with specific focus on social and repetitive behavior.

In first-time mothers, post-partum depressive symptom prospectively predict symptoms of post-traumatic stress.

Background: Symptoms of both depression and Post-Traumatic Stress Disorder (PTSD) are prevalent among first-time mothers following birth. However, the direction of the association between the two types of symptoms is unclear.

Methods: Ninety six first-time mothers giving birth via vaginal delivery (N=38), emergency C-Section (N=27) and planned C-Section (N=21) were assessed for depression and PTSD twice: Six weeks post-partum and six-weeks later.

Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA.

Following reports of emotional psychopathology in children and adults exposed to organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear-conditioning and depression-like behaviors were tested in adult mice. Concomitant changes in expression of mRNA for synaptic and soluble splice variants of acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4-10 and tested as adults for conditioned fear, sucrose preference, and forced swim.

Post-natal psychopathology and bonding with the infant among first-time mothers undergoing a caesarian section and vaginal delivery: sense of coherence and social support as moderators.

Objective: To investigate the protective role of sense of coherence (SOC) and perceived social support in the effect of emergency/elective caesarian section on post-natal psychological symptoms and impairment in mother-infant bonding.

Design: Thirty-seven women delivering via an emergency C-section, 21 via elective C-section and 38 through a vaginal delivery were assessed six weeks post-partum (Time 1) as to their post-traumatic stress disorder (PTSD) and depressive symptoms, impairment in bonding and SOC and social support. Symptoms and bonding difficulties were assessed again six weeks later (Time 2).

Postnatal diisopropylfluorophosphate enhances conditioned vigilance in adult BALB/c and C57BL/6 mice and alters expression of acetylcholinesterase splice variants.

The long-term effects of postnatal exposure to an organophosphate substance diisopropylfluorophosphate (DFP) were examined on fear conditioning in adult mice. Immediate and long-term changes in the expression of synaptic acetylcholinesterase (AChE-S) and readthrough acetylcholinesterase (AChE-R) transcripts were explored, in view of reports relating expression of these splice variants to stress and anxiety. BALB/c and C57BL/6 mice were injected daily, on postnatal days 4-10, with 1 mg/kg of DFP or saline and tested as adults for cued and contextual freezing and scanning.

Reward sensitivity and anger in euthymic bipolar disorder.

According to the hypersensitive behavioral approach system (BAS) model of bipolar disorder (BP), hypersensitivity of the BAS is a trait that should be present even in the euthymic state. This would be expected to result in increased anger and reward sensitivity, both of which are related to the approach system. This study examined these predictions through the use of tasks that assess different aspects of the BAS: reward sensitivity, anger and impulsivity.

Differential long term effects of early diisopropylfluorophosphate exposure in Balb/C and C57Bl/J6 mice.

The long-term effect of postnatal administration of a sub-toxic dose of the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP) on depression and anxiety behavior was compared in two strains of inbred mice. C57BL/6J and Balb/C mice were injected for 7 consecutive days with either 1 mg/kg DFP or saline on postnatal days 14-20. Mice were tested at age 3-4 months for initial and learned anxiety using double-exposure elevated plus maze and to a novel enclosed environment.

Using international emotional picture sets in countries suffering from violence.

It is hypothesized that ratings of emotional stimuli are affected by a constant threat of traumatic events. Ratings of valence and arousal on the International Affective Picture System from young adults in the United States were compared to those of young Israeli adults. Israelis rated the pictures as less negative and less positive than did participants from the United States.

Fear-related pictures deteriorate the performance of university students with high fear of snakes or spiders.

Despite research regarding emotional processing, it is still unclear whether fear-evoking stimuli are processed when they are irrelevant and when attention is oriented elsewhere. In this study, 63 healthy university students with high fear from snakes or spiders participated in two different experiments. In an emotional modification of the spatial cueing task, 31 subjects (5 males) were asked to detect a target letter while ignoring a neutral or fear-related distracting picture.

Strain and regional dependence of alternate splicing of acetylcholinesterase in the murine brain following stress or treatment with diisopropylfluorophosphate.

Induction of the rare readthrough variant of acetylcholinesterase (AChE-R) by an acetylcholinesterase (AChE) inhibitor or by stress was tested in four mouse strains that differ in their behavioural profiles on tests of anxiety and depression. BALB/C, C57Bl/6, C3H/He and CD-1 mouse strains were tested in the elevated plus maze in two sessions, separated by 48h. All strains, except CD-1, showed the expected reduction in open arm exploration on the second session.

On becoming a first-time mother after an emergency Caesarean section: a journey from alienation to symbolic adoption.

This qualitative research focused on the significance of subjective experience of mothers who gave birth in an emergency Caesarean section. Ten first-time mothers experiencing emergency Caesarean section were interviewed, and their narrative accounts were analyzed using Giorgi's phenomenological method. Mothers described alienation from the infant on encountering her/him; primal difficulties in holding; a 'mechanistic' pattern of childcare at home; over-apprehension and fear of a cradle-death.

Discrimination and avoidance learning in adult mice following developmental exposure to diisopropylfluorophosphate.

Exposure to acetylcholinesterase inhibitors during development was shown in the past to induce sex-dependent changes in locomotion and specific cognitive and emotional tests in rodents. Adult mice that had been treated with 0.5 mg/kg diisopropylfluorphosphate (DFP), on post-natal days 14-20 were tested on active avoidance and a set-shifting task.

Habituation, discrimination and anxiety in transgenic mice overexpressing acetylcholinesterase splice variants.

TgS and TgR transgenic mice overexpress different splice variants of acetylcholinesterase and serve as models for genetic disruption of the cholinergic system. Whereas the TgS mouse overexpresses synaptic AChE, the TgR mouse overexpresses the rare readthrough variant whose C-terminal lacks the cysteine residue which permits adherence to the membrane. The two genotypes were compared to the parent strain, FVB/N mice on locomotion, discrimination learning and anxiety behavior following two exposures to the elevated plus maze.

Effect of valproate derivatives on human brain myo-inositol-1-phosphate (MIP) synthase activity and amphetamine-induced rearing.

We have recently shown that valproate (VPA) decreases intracellular concentrations of inositol, like lithium but via a different mechanism, namely by inhibiting myo-inositol-1-phosphate (MIP) synthase. Valnoctamide (VCD) and valrocemide (VGD) are VPA derivatives which are anticonvulsants and have been shown in animal models to be significantly less teratogenic than VPA. We now show that 1 mM of either VCD or VGD drastically inhibits human brain crude homogenate MIP synthase activity.

A novel task for examining strategic planning: evidence for impairment in children with ADHD.

Children with attention deficit hyperactivity disorder (ADHD) often show poor performance on tasks that require strategic planning. To assess this ability, we developed a paper and pencil task that required consistent use of a simple test-taking strategy to maximize the number of points. The visual discrimination task with minimal cognitive demands required children to maximize their gains by responding only to outlined high-point problems and to skip the low-point problems.