Offspring Brain Weight Research Articles

Neurobehavioral Characterization of Perinatal Oxycodone-Exposed Offspring in Early Adolescence.

The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being.

Effect of <i>In Vitro</i> Culture and Embryo Transfer on Neuronal Density and Neurogenesis in the Brain of C57BL/6J Mice

The current research is aimed to determine the long-term effects of the in vitro culture (IVC) and embryo transfer (ET) on the neonatal offspring development, as well as on the adult hippocampal neuronal densities, as well hippocampal neurogenesis in С57BL/6J mice. Offspring of naturally born C57BL/6J mice (C57BL group) were compared with C57BL/6J mice born as a result of the IVC combined with ET to C57BL/6J recipient females (ET-C57BL group). At age of 3 mo., no group differences were observed in the body weight and brain-to-body ratio, although sex differences in these variables were observed. The offspring of both sexes born after IVC-ET exhibited the lower level of neurogenesis in the dentate gyrus (DG) of the hippocampus as compared to the control C57BL group. To conclude, IVC and ET exerted no major effects on body and brain weight in offspring, but affected hippocampal neurogenesis in the adult offspring of both sexes. Besides, the number of pyramidal neurons in the CA3 area of hippocampus was lower in female offspring of ET-C57BL group.

Intrauterine inflammation induced white matter injury protection by fibrinogen-like protein 2 deficiency in perinatal mice

BackgroundWhite matter injury (WMI) induced by intrauterine inflammation can cause adverse neurological outcomes. Fibrinogen-like protein 2 (FGL2)/fibroleukin is an important trigger of inflammatory responses and is involved in some cerebral diseases. However, the role of FGL2 in intrauterine inflammation-induced WMI remains unclear.MethodsLipopolysaccharide (LPS) was intraperitoneally injected into wild-type and FGL2 knockout mice to induce intrauterine inflammation. Body weight and brain weight of offspring were monitored. Major basic protein (MBP) expression was evaluated to demonstrate the myelination of offspring. To investigate the regulatory mechanism of FGL2, cytokine expression, microglial polarization, and the activation of mitogen-activated protein kinase (MAPK) signaling pathway in the offspring were analyzed.ResultsUpon LPS exposure, FGL2 knockout offspring showed a significant increase in body weight loss. MBP reduction induced by LPS was prevented in FGL2 knockout offspring. Expression levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and M1 marker CD86 were suppressed, while the expression levels of anti-inflammatory cytokines IL-10 and M2 marker CD206 were increased. FGL2 deficiency significantly inhibited the phosphorylation of p38MAPK and c-Jun N-terminal kinase (JNK) protein.ConclusionsFGL2 deficiency can ameliorate WMI induced by intrauterine inflammation, reducing inflammatory cascade and improving hypomyelination, through the regulation of microglial polarization and MAPK signaling pathways.ImpactIntrauterine inflammation induces WMI leading to severe neurological sequelae. FGL2 plays an important role in the progression of WMI induced by intrauterine inflammation.FGL2 deficiency can protect against WMI by inhibiting p38 MAPK and JNK phosphorylation, regulating microglia polarization, and reducing inflammation response.FGL2 could be a novel molecular target for protecting against WMI induced by intrauterine inflammation.

Effect of prenatal administration of venlafaxine on postnatal development of rat offspring

About 3% of pregnant women are treated with antidepressant drugs during gestation. After delivery the number of treated women increases to 5 to 7%. Most prescribed antidepressants in pregnancy are selective serotonin re-uptake inhibitors and/or serotonin and noradrenaline re-uptake inhibitors, such as fluoxetine, paroxetine, sertraline, citalopram and venlafaxine (VENF). Despite the fact that VENF has been assigned to pregnancy category C by the FDA, experimental studies with this drug are rare. The aim of this pilot study was to investigate the effect of prenatal administration of VENF on early postnatal development of rat offspring and selected biochemical variables at weaning of pups. Pregnant female Wistar rats were treated with VENF from day 15 to 20 of gestation at the doses of 7.5, 37.5 and 70 mg/kg. Females were allowed to spontaneously deliver their pups. After delivery the pups were inspected for viability, gross malformation and they were weighed on day 0, 4 and 21 post partum. On day 21 post partum, the pups were killed, brains were removed from the skulls and blood samples were collected for biochemical assay (proteins, glucose-GOD, glucose-HEX, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and total antioxidant status). The study showed that prenatal VENF administration resulted in a mild maternal intoxication manifested by decreased body weight gain of pregnant females. There was no effect of the drug tested on the body and brain weights of offspring. No obvious morphological alterations were observed in the delivered pups. Similarly, there were no changes in the selected biochemical variables determined.

Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats

The present study determined the effect of maternal nicotine exposure during the early developmental period on AT 1R and AT 2R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg/kg/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine treatment. Nicotine significantly increased brain AT 1R in fetuses at gestation 15 and 21 days and decreased central AT 2R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT 1R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT 2R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT 1R mRNA abundance did not change during postnatal development, AT 2R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT 1R mRNA in the female offspring. In contrast, it decreased AT 2R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT 1R/AT 2R mRNA ratio in the brain of adult animals, which was significantly up-regulated in nicotine-treated animals with females being more prominent than males. The results demonstrate that perinatal nicotine exposure alters AT 1R and AT 2R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.

A preliminary investigation of the effects of maternal ethanol intake during gestation and lactation on brain adenosine A 1 receptor expression in rat offspring

Ethanol exposure during fetal development can result in behavioral and neurological deficits, including reduced cognitive functions, retarded growth, and craniofacial abnormalities. Adenosine is an endogenous neuromodulator that fine-tunes the release and/or synaptic activities of several neurotransmitters, including glutamate, dopamine, and serotonin. Our aim was to determine whether ethanol exposure during early development affects adenosine receptors, particularly the A 1 receptor subtype, in adult rats. Female rats were given water or 15% (vol/vol) ethanol in water prior to mating and throughout gestation and lactation. Sixty-day-old male rat offspring from these dams were randomly selected and assayed for adenosine A 1 receptor expression in four brain areas: cortex, cerebellum, hippocampus, and striatum. Our results indicate that ethanol intake by dams decreased body and brain weights of offspring and reduced both A 1 receptor mRNA and protein density in cortex and cerebellum. These preliminary findings indicate that ethanol intake by dams during pregnancy and lactation can affect adenosine A 1 receptor signalling in the offspring. A pair-fed controlled study is warranted to explore these findings further.

Hipertensão Arterial Experimental e Prenhez em Ratas: Repercussões sobre o Peso, Comprimento e Órgãos dos Recém-nascidos

Purpose: to study the repercussion of arterial hypertension regarding body weight gain and body length, as well as liver and brain weight of offspring. Methods: a total of 82 animals in reproductive age were used. They were randomly assigned to 4 different groups (control, handled, nephrectomized and hypertensive). Renal hypertension was produced by a controlled constriction of the main left renal artery and contralateral nephrectomy, according to the technique described by Goldblatt (Goldblatt I: one kidney - one clip hypertension). Afterwards, they were distributed among nonpregnant and pregnant groups. The following newborn groups resulted from the pregnant groups: RN-C (control-newborn group of pregnant rats without surgical treatment), RN-M (manipulation-newborn group of the pregnant rats with surgical manipulation), RN-N (nephrectomized-newborn group of pregnant rats with nephrectomy) and Rn-H (hypertensive-newborn group of pregnant rats with hypertension). Results: the RN-N and RN-H groups showed body weight gain ( = 3,64 ± 0,50; = 3,37 ± 0,44), body length ( = 3,89 ± 0,36; = 3,68 ± 0,32) and brain weight ( = 0,16 ± 0,01; = 0,16 ± 0,05), respectively, smaller than the control group ( = 5,40 ± 0,51; = 4,95 ± 0,23 and = 0,22 ± 0,04, respectively). In addition, the RN-H group showed the lowest liver weight ( = 0,22 ± 0,03) compared with the other three groups. Conclusion: after statistical analysis, the results obtained showed that the arterial hypertension determined a reduction in body weight, body length, and liver and brain weight of the offspring.

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.

Prenatal haloperidol exposure: Effects on brain weights and caudate neurotransmitter levels in rats

Monoamines may exert a trophic effect on early brain development. To assess the role of dopamine in prenatal neurological development of the rat, haloperidol (HAL) was given in daily 2.5 or 5 mg/kg SC doses to dams over gestational days 6 to 20. This treatment regime did not enhance fetal mortality, but did produce reliable, if modest, stunting of the body and brain weight of offspring. The 5 mg/kg HAL dose consistently reduced offspring brain weight to roughly 90% of controls. This effect was probably permanent, in that it was seen throughout maturation and in adults as late as 140 days of postnatal age. Appropriate controls showed that this effect was not due to drug-induced reductions in food intake, to the presence of HAL in maternal milk, or to behavioral abnormalities in HAL-exposed dams. These effects had, at best, modest regional specificity, in that most brain regions were affected, independently of degree of dopaminergic innervation. Closer investigation of HAL effects on the striatum suggested that this permanent weight reduction was not accompanied by alterations in striatal concentrations of monoamines, monoamine metabolites, amino acids, choline, acetylcholine, DNA, protein, or water. It is concluded that prenatal HAL does stunt growth, but that this effect may not involve a direct drug influence restricted to the fetal dopamine system in the brain.