PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.

Sickle cell disease is a growing health burden afflicting millions around the world. Clinical observation and laboratory studies have shown that the severity of sickle cell disease is ameliorated in individuals who have elevated levels of fetal hemoglobin. Additional pharmacologic agents to induce sufficient fetal hemoglobin to diminish clinical severity is an unmet medical need.

Roles of Nuclear Orphan Receptors TR2 and TR4 during Hematopoiesis.

TR2 and TR4 (NR2C1 and NR2C2, respectively) are evolutionarily conserved nuclear orphan receptors capable of binding direct repeat sequences in a stage-specific manner. Like other nuclear receptors, TR2 and TR4 possess important roles in transcriptional activation or repression with developmental stage and tissue specificity. TR2 and TR4 bind DNA and possess the ability to complex with available cofactors mediating developmental stage-specific actions in primitive and definitive erythrocytes.

Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats.

The present study was aimed at evaluating the influence of the subchronic exposure of cadmium (Cd), copper (Cu), and nickel (Ni) mixtures on affective behaviors, memory impairment, and oxidative stress (OS) in the hippocampus. Thirty male Wistar rats were divided into 5 equal groups. Group 1 (control) received a saline solution (NaCl 0.

Neuroprotective effect of melatonin on nickel-induced affective and cognitive disorders and oxidative damage in rats.

The present work is carried out to explore the neuroprotective potential of Melatonin(Mel), on Ni-induced neurobehavioral, biochemical and histological alterations in male and female rats. The rats were intraperitoneally administered by nickel chloride (NiCl2, 1 mg/kg) and Mel (4 mg/kg) for 60 days. A neurobehavioral assessment was performed.

Animal Models of Early-Life Adversity.

From the prenatal period throughout the first years of life, the brain undergoes its most rapid development, a period during which it is highly sensitive to external experiences. The timing of brain development differs from one region to another, as it also differs between substrates, neurotransmitter systems, and central endocrine circuitries. These discontinuities are part of the "critical periods of brain development.

Effects of lipopolysaccharide administration and maternal deprivation on anxiety and depressive symptoms in male and female Wistar rats: Neurobehavioral and biochemical assessments.

Introduction: Preclinical studies of early-life adversity (ELA) have highlighted the role of postnatal stress in the emergence and persistence of anxiety and depressive disorders. In this study, we compared anxious and depressive behaviors and oxidation levels in male and female Wistar rats subjected to three ELAs (lipopolysaccharide (LPS) induced, maternal deprivation (MD), or combination of the two stressors).

Methods: Rats were split into four groups: control group which received an intraperitoneal (IP) injection of saline on postnatal day (PND) 1, LPS-treated group which received an IP injection of LPS on PND1, MD group which was exposed to a 24-hour period of isolation on PND9, and LPS-treated/MD group which received an IP injection of LPS on PND1 then was exposed to a 24-hour period of isolation on PND9.