Paternal Morphine Alters Offspring Circulating Beta-Endorphin and Corticosterone Responses to Oxycodone and Cocaine.

Background: The opioid epidemic is leading to increased opioid use in adolescent populations. A growing body of evidence suggests that taking opioids during adolescence can disrupt normal development and impact future offspring. This study investigates the impact of paternal morphine exposure during adolescence on the hypothalamic-pituitary-adrenal (HPA) axis and release of endorphins in the offspring.

Differential Effects of Prenatal Buprenorphine and Methadone on Postnatal Growth and Gene Expression in the Nucleus Accumbens.

Methadone and buprenorphine are commonly prescribed during pregnancy to maintain recovery and prevent symptoms of withdrawal in women with opioid use disorder. Infants prenatally exposed to medications for opioid use disorder (MOUD), however, commonly show signs of neonatal opioid withdrawal syndrome (NOWS), which can include feeding-related issues like hyperphagia. To investigate the effects of prenatal MOUD exposure on feeding behavior, female Sprague-Dawley rats were implanted with osmotic minipumps filled with methadone, buprenorphine, or saline and subsequently mated.

Clot-Targeted Nanogels for Dual-Delivery of AntithrombinIII and Tissue Plasminogen Activator to Mitigate Disseminated Intravascular Coagulation Complications.

Disseminated intravascular coagulation (DIC) is a pathologic state that follows systemic injury and other diseases. Often a complication of sepsis or trauma, DIC causes coagulopathy associated with paradoxical thrombosis and hemorrhage. DIC upregulates the thrombotic pathways while simultaneously downregulating the fibrinolytic pathways that cause excessive fibrin deposition, microcirculatory thrombosis, multiorgan dysfunction, and consumptive coagulopathy with excessive bleeding.

Neuroplasticity-related genes correlate with individual differences in distinct phases of oxycodone self-administration in male rats.

Opioid use disorder (OUD) is a chronic condition associated with long-lasting molecular and behavioral changes. Animals with prolonged access to opioids develop behaviors similar to human OUD. Identifying associated molecular changes can provide insight to underpinnings that lead to or maintain OUD.

Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.

Rationale: Transgenerational effects of preconception morphine exposure in female rats have been reported which suggest that epigenetic modifications triggered by female opioid exposure, even when that exposure ends several weeks prior to pregnancy, has significant ramifications for their future offspring.

Objective: The current study compares two mouse strains with well-established genetic variation in their response to mu opioid receptor agonists, C57BL/6J (BL6) and 129S1/svlmJ (129) to determine whether genetic background modifies the impact of preconception opioid exposure.

Methods: Adolescent females from both strains were injected daily with morphine for a total of 10 days using an increasing dosing regimen with controls receiving saline.

Effects of Maternal Separation on Effort-based Responding for Sucrose Are Associated with c-Fos Expression in the Nucleus Accumbens Core.

In both people and animals, exposure to adverse experiences early in life can alter neurodevelopment and lead to long-term behavioral effects, including effects on reward processing. In the current study, we use a well-validated rodent model of maternal neglect, maternal separation (MS), to investigate the impact of early life adversity on reward learning and motivation and identify associated modifications in cellular activation in reward-relevant areas. Litters of Long-Evans rats were separated from the dam for either 15 min (brief) or 180 min (prolonged)/day from postnatal day (PND)2 to PND14.

Association between high-sensitivity cardiac troponin I and fall-related hospitalisation in women aged over 70 years.

Objective: To examine the association between high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, muscle function decline and 14.5-year fall-related hospitalisation risk in women aged over 70 years.

Methods: 1179 ambulatory community-dwelling women aged over 70 years with subclinical levels of hs-cTnI (ie, <15.

Circulating lipocalin-2 and features of metabolic syndrome in community-dwelling older women: A cross-sectional study.

Lipocalin-2 (LCN2) is released by several cell types including osteoblasts and adipocytes and has been suggested as a marker of renal dysfunction, metabolic syndrome (MetS) and type 2 diabetes (T2D). Whether LCN2 is linked to these diseases in older women remains unknown. This study investigated whether LCN2 is related to features of MetS and T2D in older women.

The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial.

Background And Objective: The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2-4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy.

Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women.

This study examined the association between dietary Vitamin K1 intake with fracture-related hospitalizations over 14.5 years in community-dwelling older Australian women ( = 1373, ≥70 years). Dietary Vitamin K1 intake at baseline (1998) was estimated using a validated food frequency questionnaire and a new Australian Vitamin K nutrient database, which was supplemented with published data.

Intergenerational effects of preconception opioids on glucose homeostasis and hepatic transcription in adult male rats.

Adolescence represents a period of significant neurodevelopment during which adverse experiences can lead to prolonged effects on disease vulnerability, including effects that can impact future offspring. Adolescence is a common period for the initiation of drug use, including the use of opioids. Beyond effects on central reward, opioids also impact glucose metabolism, which can impact the risk of diabetes.

HPA axis dysfunction during morphine withdrawal in offspring of female rats exposed to opioids preconception.

Opioid use and abuse remain a significant public health problem, particularly in the United States. Indeed, it is estimated that up to 10% of youths (age 12-18) have taken opioids illicitly. A growing body of evidence suggests that this level of widespread opioid exposure can have effects that extend to subsequent generations.

Transgenerational effects on anxiety-like behavior following adolescent morphine exposure in female rats.

Global opioid use and misuse remains high, despite efforts to decrease rates of prescribing and diversion. Chronic exposure to opioids, particularly during critical periods of development, can lead to long-lasting effects, including effects that may extend to future generations. Using a rodent model, we have demonstrated significant transgenerational effects of female adolescent morphine exposure, despite the absence of in utero drug exposure.

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women.

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations.

Association between Circulating Osteocalcin and Cardiometabolic Risk Factors following a 4-Week Leafy Green Vitamin K-Rich Diet.

Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors.

Materials And Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study.

Serum Midkine, estimated glomerular filtration rate and chronic kidney disease-related events in elderly women: Perth Longitudinal Study of Aging Women.

Midkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.

The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals.

Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism.

Oxycodone Decreases Dendritic Complexity in Female but not Male Rat Striatal Neurons In Vitro.

The use of oxycodone in the past two decades has dramatically risen, yet the amount of research regarding how it impacts neuronal health is lacking. As prescription use and misuse in women of reproductive age increases there has been a corresponding increase in the number of infants who have been exposed to oxycodone in utero. Given the critical role of the striatum in motor control and reward regulation, the aim of the current study was to examine the effects of oxycodone on developing rat striatal neurons.

A history of opioid exposure in females increases the risk of metabolic disorders in their future male offspring.

Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation.

Paternal morphine exposure induces bidirectional effects on cocaine versus opioid self-administration.

The United States is in the midst of an opioid epidemic and is thus experiencing unprecedented levels of opioid exposure. A growing body of evidence has demonstrated that this may have consequences on multiple generations. The current set of experiments examined the effect of male adolescent opioid exposure on cocaine and opioid self-administration in the F1 generation.

Osteocalcin and its forms across the lifespan in adult men.

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease.

Multi-, Inter-, and Transgenerational Effects of Drugs of Abuse on Behavior.

Transgenerational epigenetic inheritance is a burgeoning field that has recently garnered much attention. A growing body of evidence identifies behavioral phenotypes associated with inter-, multi-, and transgenerational studies following a wide variety of parental exposures. This chapter in current topics in behavioral neurogenomics examines the evidence for the presence of behavioral phenotypes and, in particular, the varied and often opposite behavioral responses observed with protocol shifts.

Challenges to the parental brain: Neuroethological and translational considerations.

Extending from research documenting adaptive parental responses in nonthreatening contexts, the influences of various neuroethological and physiological challenges on effective parenting responses are considered in the current review. In natural habitats, rodent family units are exposed to predators, compromised resources, and other environmental stressors that disrupt HPA axis functions. With the additional physiological demands associated with caring for offspring, alterations in stress-related neuroendocrine responsiveness contribute to adaptive responses in many challenging contexts.