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.

Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix.

Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats.

Early life cancer and chemotherapy lead to cognitive deficits related to alterations in microglial-associated gene expression in prefrontal cortex.

Children that survive leukemia are at an increased risk for cognitive difficulties. A better understanding of the neurobiological changes in response to early life chemotherapy will help develop therapeutic strategies to improve quality of life for leukemia survivors. To that end, we used a translationally-relevant mouse model consisting of leukemic cell line (L1210) injection into postnatal day (P)19 mice followed by methotrexate, vincristine, and leucovorin chemotherapy.

Photovoltaics at multi-terawatt scale: Waiting is not an option.

25% annual PV growth is possible over the next decade.

Perinatal Morphine Exposure Leads to Sex-Dependent Executive Function Deficits and Microglial Changes in Mice.

Children exposed prenatally to opioids are at an increased risk for behavioral problems and executive function deficits. The prefrontal cortex (PFC) and amygdala (AMG) regulate executive function and social behavior and are sensitive to opioids prenatally. Opioids can bind to toll-like receptor 4 (TLR4) to activate microglia, which may be developmentally important for synaptic pruning.

Rates of substance and polysubstance use through universal maternal testing at the time of delivery.

Objective: To report substance and polysubstance use at the time of delivery.

Study Design: A cross-sectional study was performed on mothers consented for universal drug testing (99%) during hospital admission at six delivery hospitals in Cincinnati, Ohio. Mass spectrometry urinalysis detected positivity rates of 46 substances.

Translationally relevant mouse model of early life cancer and chemotherapy exposure results in brain and small intestine cytokine responses: A potential link to cognitive deficits.

Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life.

Improving translational relevance: The need for combined exposure models for studying prenatal adversity.

Prenatal environmental adversity is a risk factor for neurodevelopmental disorders (NDDs), with the neuroimmune environment proposed to play a role in this risk. Adverse maternal exposures are associated with cognitive consequences in the offspring that are characteristics of NDDs and simultaneous neuroimmune changes that may underlie NDD risk. In both animal models and human studies the association between prenatal environmental exposure and NDD risk has been shown to be complex.

Voluntary alcohol consumption is increased in female, but not male, oxytocin receptor knockout mice.

Introduction: The oxytocin (Oxt) system, while typically associated with the neural regulation of social behaviors, also plays a role in an individual's vulnerability to develop alcohol use disorders (AUD). In humans, changes to the Oxt system, due to early life experience and/or genetic mutations, are associated with increased vulnerability to AUD. While a considerable amount is known about Oxt's role in AUD in males, less is known or understood, about how Oxt may affect AUD in females, likely due to many clinical and preclinical studies of AUD not directly considering sex as a biological variable.

Differential impact of stress and environmental enrichment on corticolimbic circuits.

Stress exposure can produce profound changes in physiology and behavior that can impair health and well-being. Of note, stress exposure is linked to anxiety disorders and depression in humans. The widespread impact of these disorders warrants investigation into treatments to mitigate the harmful effects of stress.

Prefrontal Cortex Regulates Chronic Stress-Induced Cardiovascular Susceptibility.

Background The medial prefrontal cortex is necessary for appropriate appraisal of stressful information, as well as coordinating visceral and behavioral processes. However, prolonged stress impairs medial prefrontal cortex function and prefrontal-dependent behaviors. Additionally, chronic stress induces sympathetic predominance, contributing to health detriments associated with autonomic imbalance.

Adolescent microglia play a role in executive function in male mice exposed to perinatal high fat diet.

In humans, excessive gestational weight gain during pregnancy is associated with an increased risk for executive function deficits in the offspring. Our previous work has confirmed this finding in mice, as offspring from dams fed a 60% high fat (HF) diet during breeding, gestation, and lactation demonstrate impulsive-like behavior in the 5 choice serial reaction time task (5CSRTT). Because the prefrontal cortex (PFC), which plays a key role in executive function, undergoes substantial postnatal adolescent pruning and microglia are actively involved in synaptic refinement, we hypothesized that microglia may play a role in mediating changes in brain development after maternal HF diet, with a specific focus on microglial activity during adolescence.

Loss of Environmental Enrichment Elicits Behavioral and Physiological Dysregulation in Female Rats.

Chronic stress drives behavioral and physiological changes associated with numerous psychiatric disease states. In rodents, the vast majority of chronic stress models involve imposition of external stressors, whereas in humans stress is often driven by internal cues, commonly associated with a sense of loss. We previously exposed groups of rats to environmental enrichment (EE) for a protracted period (1 month), followed by removal of enrichment (ER), to induce an experience of loss in male rats.

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy.

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e.

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood.

Behavioral and physiological consequences of enrichment loss in rats.

Significant loss produces the highest degree of stress and compromised well-being in humans. Current rodent models of stress involve the application of physically or psychologically aversive stimuli, but do not address the concept of loss. We developed a rodent model for significant loss, involving removal of long-term access to a rewarding enriched environment.

Divergent effects of repeated restraint versus chronic variable stress on prefrontal cortical immune status after LPS injection.

Previous work from our group has shown that chronic homotypic stress (repeated restraint - RR) increases microglial morphological activation in the prefrontal cortex (PFC), while chronic heterotypic stress (chronic variable stress - CVS) produces no such effect. Therefore, we hypothesized that stressor modality would also determine the susceptibility of the PFC to a subsequent inflammatory stimulus (low dose lipopolysaccharide (LPS)). We found that RR, but not CVS, increased Iba-1 soma size in the PFC after LPS injection, consistent with microglial activation.