Transcriptome sequencing of gene expression in the brain of the HIV-1 transgenic rat.

The noninfectious HIV-1 transgenic (HIV-1Tg) rat was developed as a model of AIDs-related pathology and immune dysfunction by manipulation of a noninfectious HIV-1(gag-pol) virus with a deleted 3-kb SphI-MscI fragment containing the 3' -region of gag and the 5' region of pol into F344 rats. Our previous studies revealed significant behavioral differences between HIV-1Tg and F344 control rats in their performance in the Morris water maze and responses to psychostimulants. However, the molecular mechanisms underlying these behavioral differences remain largely unknown.

Ethanol concentration-dependent alterations in gene expression during acute binge drinking in the HIV-1 transgenic rat.

Background: Binge drinking of high ethanol (EtOH) concentration beverages is common among young adults and can be a risk factor for exposure to sexually transmitted diseases, including HIV-1. We used a novel noninfectious HIV-1 transgenic (HIV-1Tg) rat model that mimics HIV-1 patients in terms of altered immune responses and deficits in cognitive learning and memory to investigate EtOH concentration-dependent effects on 48 alcohol-modulated genes during binge EtOH administration.

Methods: HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.

Involvement of the NLRP3 inflammasome in the modulation of an LPS-induced inflammatory response during morphine tolerance.

Background: Morphine is widely used for its analgesic effects. In addition to its high potential for addiction and tolerance, morphine also induces immunosuppression. Inflammasomes, NLRP3 being the most characterized, is a platform for activation of pro-inflammatory cytokines, particularly IL-1β.

Interleukin-1 beta-induced up-regulation of opioid receptors in the untreated and morphine-desensitized U87 MG human astrocytoma cells.

Background: Interleukin-1beta (IL-1β) is a pro-inflammatory cytokine that can be produced in the central nervous system during inflammatory conditions. We have previously shown that IL-1β expression is altered in the rat brain during a morphine tolerant state, indicating that this cytokine may serve as a convergent point between the immune challenge and opiate mediated biological pathways. We hypothesized that IL-1β up-regulates opioid receptors in human astrocytes in both untreated and morphine-desensitized states.

Age- and ethanol concentration-dependent effects of acute binge drinking in the HIV-1 transgenic rat.

Background: Binge drinking is common in young people. Alcoholic beverages vary significantly in their ethanol (EtOH) concentration (alcohol by volume). We previously showed EtOH concentration-dependent activation of the hypothalamic supraoptic nucleus.

Opioid receptor expression in human brain and peripheral tissues using absolute quantitative real-time RT-PCR.

Background: The actions of endogenous opioid peptides are mediated by 3 main classes of opioid receptors; mu (MOR), kappa (KOR), and delta (DOR).

Methods: We developed an absolute quantitative real-time reverse transcriptase PCR (AQ-rt-RT-PCR) assay to quantify MOR, DOR, and KOR mRNA in 22 human tissues.

Results: MOR mRNA was greatly enriched (12-20×10(6)copies/μg) in the cerebellum, nucleus accumbens, and caudate nucleus; moderate (6×10(6)copies/μg) in the dorsal root ganglion, spinal cord, and adrenal gland; low (2×10(4)copies/μg) in the pancreas and small intestine; and absent in the lung, spleen, kidney, heart, skeletal muscle, liver, and thymus.

Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease.

We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer's disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid-beta (Abeta){1-40} in both brain extracts (52% reduction, p= 0.

Chronic Leptin Supplementation Ameliorates Pathology and Improves Cognitive Performance in a Transgenic Mouse Model of Alzheimer's Disease.

We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer's disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid-beta (Abeta){1-40} in both brain extracts (52% reduction, p= 0.

Leptin inhibits glycogen synthase kinase-3beta to prevent tau phosphorylation in neuronal cells.

We have previously demonstrated that Leptin reduces extracellular amyloid beta (Abeta) protein both in vitro and in vivo, and intracellular tau phosphorylation in vitro. Further, we have shown that these effects are dependent on activation of AMP-activated protein kinase (AMPK) in vitro. Herein, we investigated downstream effectors of AMPK signaling directly linked to tau phosphorylation.

Leptin: a novel therapeutic strategy for Alzheimer's disease.

Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin has been shown to reduce the amount of extracellular amyloid beta, both in cell culture and animal models, as well as to reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models.

Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells.

Leptin, which serves as a lipid-modulating hormone to control metabolic energy availability, is decreased in Alzheimer's disease (AD) patients, and serum levels are inversely correlated to severity of dementia. We have previously described the effects of leptin in reducing amyloid beta protein both in vitro and in vivo, and tau phosphorylation in vitro. Herein, we systematically investigated the signaling pathways activated by leptin, leading to these molecular endpoints, to better understand its mechanism of action.

Leptin reduces Alzheimer's disease-related tau phosphorylation in neuronal cells.

Leptin is a centrally acting hormone controlling metabolic pathways. Recently, it was shown that leptin can reduce amyloid beta levels both in vitro and in vivo. Herein, phosphorylation of tau was investigated following treatment of neuronal cells with leptin and insulin.