Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore hypothesis that maternal cocaine exposure could alter fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg twice daily on gestational days 8-19. Male pups from each ten litters control groups analyzed at 3 (P3) 30 (P30) postnatum. Global DNA methylation, methylated...

Background: Globally, sub-Saharan Africa bears the greatest burden of disease. Strengthened research capacity to understand social determinants health among different African populations is key addressing drivers poor and developing interventions improve outcomes systems in region. Yet, continent clearly lacks centers excellence that can generate a strong evidence base address region's socio-economic problems.Objective program overview: We describe recently launched Consortium for Advanced...

Dopamine activates phospholipase C in discrete regions of the mammalian brain, and this action is believed to be mediated through a D₁-like receptor. Although multiple lines evidence exclude role for D₁ subtype receptors phosphoinositide response, D₅ has not been similarly examined. Here, mice lacking dopamine were tested agonist-induced signaling both vitro vivo. The results show that hippocampal, cortical, striatal tissues receptor knockout significantly or...

Cocaine exhibits high liability for inducing addictive behaviors, but the mechanisms of neuroplasticity underlying behavioral effects remain unclear. As a crucial mediator in diverse functional models, brain-derived neurotrophic factor (BDNF) could contribute to addiction-related neuroplasticity. Here, we addressed hypothesis that cocaine increases synaptic dopamine, which induces BDNF protein expression initiate behavior rat. An enzyme-linked immunosorbent assay was used measure rat...

Recent studies showed that dopamine or D1 receptor-selective agonists increased brain-derived neurotrophic factor (BDNF) mRNA and protein expression in neuronal cultures, this action was blocked by SCH23390. Moreover, SKF38393 activated Trk receptors downstream signaling striatal neurons. This study examined whether induce the of BDNF rat brain tissue. Acute slice preparations were incubated with Hibernate A medium measured a sensitive enzyme-linked immunosorbent assay. Results tissue slices...

siRNA is currently the most widely studied form of RNAi, and it has promising therapeutic potential not just in cancer but also other diseases such as autoimmune infectious diseases. However, efficient delivery to target cells being limited by lack an effective system that ensures transfection into while protecting encapsulated from nuclease. We hypothesized a hybrid nanoparticle composed human IgG poloxamer-188, stealth polymer, will efficiently deliver mutated KRAS A549 cells, leading...

Abstract Background Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology remains obscure, antidepressant medications increase synaptic levels monoamine neurotransmitters in brain regions associated with disease. Monoamine transmitters activate multiple signaling cascades some which have been investigated as potential mediators or drug action. However, diacylglycerol arm phosphoinositide has not systematically investigated,...

Recent studies demonstrate that diverse antidepressant agents increase the cellular production of nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade downstream phosphatidylinositide signaling disrupted behavioral effects rats. However, responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could...

<b>Abstract ID 100107</b> <b>Poster Board 529</b> Dopamine receptor stimulation facilitates phosphatidylinositol resynthesis, thus amplifying subsequent responses to activation of phospholipase C-coupled receptors. Phosphatidylinositol synthesis critically depends on the nucleolipid CDP-diacylglycerol. robustly increases microsomal CDP-diacylglycerol biosynthesis through D₁-like receptors, particularly D₅ subtype majority which are intracellularly localized. Here, we...

Dopamine stimulates CDP-diacylglycerol biosynthesis through D1-like receptors, particularly the D5 subtype most of which is intracellularly localized. regulates phosphatidylinositol-4,5-bisphosphate-dependent signaling cascades by serving as obligatory substrate for phosphatidylinositol biosynthesis. Here, we used acute and organotypic brain tissues cultured cells to explore mechanism extracellular dopamine acts modulate intracellular CDP-diacylglycerol. stimulated in neural lacking...

While induction of neurogenesis probably contributes to the clinical efficacy antidepressant agents, it remains unclear whether antidepressants induce neural cell proliferation, promote neuronal differentiation, and/or enhance survival newly differentiated neurons. This study addressed these mechanisms using mouse fetal cortical precursor cells and RenCell human progenitor line. The imipramine fluoxetine concentration‐dependently increased proliferation cells. Differentiation into phenotype...

Physostigmine, or eserine, is an alkaloid found in the Calabar bean (eséré), Physostigma venenosum (Balfour). The scientific discovery of physostigmine played a pivotal role our understanding chemical neurotransmission and emergence pharmacology as science. Efik people Old Calabar, present day Cross River State Nigeria, used ordeal poison to determine if persons accused certain allegations such witchcraft were guilty innocent. Scottish missionaries working witnessed eséré trials attended...