Dynamic regulation of BDNF gene expression by estradiol and lncRNA HOTAIR.

Brain derived neurotrophic factor (BDNF) is a major neurotransmitter that controls growth and maintenance of neurons and its misregulation is linked to neurodegeneration and human diseases. Estradiol (E2) is well-known to regulate the process of differentiation and plasticity of hippocampal neurons. Here we examined the mechanisms of BDNF gene regulation under basal conditions and under stimuli such as E2.

Interactions between estradiol and ERK, but not mTOR, signaling is necessary for enhanced cocaine-induced conditioned place preference in female rats.

Women rapidly progress from recreational cocaine use to dependence, consume greater quantities of cocaine, experience more positive subjective effects of cocaine and have higher incidences of relapse during abstinence. These effects have been replicated in animal models of cocaine addiction and indicate an enhanced sensitivity and therefore, vulnerability of females to cocaine addiction. Furthermore, it has been demonstrated that estradiol (E2) is a key mediator of the aforementioned effects of cocaine in women and female animals.

Sex Differences and the Role of Estradiol in Mesolimbic Reward Circuits and Vulnerability to Cocaine and Opiate Addiction.

Although both men and women become addicted to drugs of abuse, women transition to addiction faster, experience greater difficulties remaining abstinent, and relapse more often than men. In both humans and rodents, hormonal cycles are associated with females' faster progression to addiction. Higher concentrations and fluctuating levels of ovarian hormones in females modulate the mesolimbic reward system and influence reward-directed behavior.

Sex differences in the expression of morphine withdrawal symptoms and associated activity in the tail of the ventral tegmental area.

Recent studies, in male rodents, have begun to elucidate a role for the GABAergic neurons in the tail of the ventral tegmental area (tVTA) in morphine withdrawal. To date, the mechanisms underlying morphine withdrawal have been studied almost exclusively in male animals. As a result, there is a considerable gap in our current understanding of the processes underlying sex differences in morphine withdrawal behaviors and its effects on cellular activity in the tVTA in females.

Experience with code-switching modulates the use of grammatical gender during sentence processing.

Using code-switching as a tool to illustrate how language experience modulates comprehension, the visual world paradigm was employed to examine the extent to which gender-marked Spanish determiners facilitate upcoming target nouns in a group of Spanish-English bilingual code-switchers. The first experiment tested target Spanish nouns embedded in a carrier phrase (Experiment 1b) and included a control Spanish monolingual group (Experiment 1a). The second set of experiments included critical trials in which participants heard code-switches from Spanish determiners into English nouns (e.

Exposure to morphine-associated cues increases mu opioid receptor mRNA expression in the nucleus accumbens of Wistar Kyoto rats.

The Wistar-Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability as it exhibits pronounced behavioral inhibition, passive avoidance, exaggerated startle response, enhanced HPA-axis activation, and active avoidance that is resistant to extinction. Accumulating evidence suggests that WKY rats respond differently to rewarding stimuli when compared to outbred strains of rat. Conditioned responding to drug-associated cues is linked with alterations in the activation of mu opioid receptors (MOR) and kappa opioid receptors (KOR) in the nucleus accumbens (NAc).

Endocrine disrupting chemical, bisphenol-A, induces breast cancer associated gene HOXB9 expression in vitro and in vivo.

HOXB9 is a homeobox-containing gene that plays a key role in mammary gland development and is associated with breast and other types of cancer. Here, we demonstrate that HOXB9 expression is transcriptionally regulated by estradiol (E2), in vitro and in vivo. We also demonstrate that the endocrine disrupting chemical bisphenol-A (BPA) induces HOXB9 expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of ovariectomized (OVX) rats.

Local field potentials in the ventral tegmental area during cocaine-induced locomotor activation: Measurements in freely moving rats.

The ventral tegmental area (VTA) has been established as a critical nucleus for processing behavioral changes that occur during psychostimulant use. Although it is known that cocaine induced locomotor activity is initiated in the VTA, not much is known about the electrical activity in real time. The use of our custom-designed wireless module for recording local field potential (LFP) activity provides an opportunity to confirm and identify changes in neuronal activity within the VTA of freely moving rats.

Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.

HOXC6 is a homeobox-containing gene associated with mammary gland development and is overexpressed in variety of cancers including breast and prostate cancers. Here, we have examined the expression of HOXC6 in breast cancer tissue, investigated its transcriptional regulation via estradiol (E2) and bisphenol-A (BPA, an estrogenic endocrine disruptor) in vitro and in vivo. We observed that HOXC6 is differentially over-expressed in breast cancer tissue.

Bilingualism, Mind, and Brain.

The use of two or more languages is common in most of the world. Yet, until recently, bilingualism was considered to be a complicating factor for language processing, cognition, and the brain. The past 20 years have witnessed an upsurge of research on bilingualism to examine language acquisition and processing, their cognitive and neural bases, and the consequences that bilingualism holds for cognition and the brain over the life span.

Brain expression of pCREB in rats exposed to consummatory successive negative contrast.

A 32-to-4% sucrose devaluation leads to suppression of consummatory behavior relative to unshifted 4% sucrose controls. This is accompanied by an emotional response inducing memory consolidation. Expression levels of phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB, a marker of synaptic plasticity) were higher after the first devaluation session than after the second in prelimbic cortex, anterior cingulate cortex, and dorso-medial striatum.

Non-scanning fiber-optic near-infrared beam led to two-photon optogenetic stimulation in-vivo.

Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in transgenic mouse models.

Histone methyltransferase EZH2 is transcriptionally induced by estradiol as well as estrogenic endocrine disruptors bisphenol-A and diethylstilbestrol.

Enhancer of Zeste homolog 2 (EZH2), a methyltransferase specific to histone 3 lysine 27, is a critical player in gene silencing and is overexpressed in breast cancer. Our studies demonstrate that EZH2 is transcriptionally induced by estradiol in cultured breast cancer cells and in the mammary glands of ovariectomized rats. EZH2 promoter contains multiple functional estrogen-response elements.

Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.

Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors.

Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo.

Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES). Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat.

Sex differences in the neurobiology of drug addiction.

Epidemiological data demonstrate that while women report lower rates of drug use than men, the number of current drug users and abusers who are women continues to increase. In addition women progress through the phases of addiction differently than men; women transition from casual drug use to addiction faster, are more reactive to stimuli that trigger relapse, and have higher rates of relapse then men. Sex differences in physiological and psychological responses to drugs of abuse are well documented and it is well established that estrogen effects on dopamine (DA) systems are largely responsible for these sex differences.

Activation of extracellular signal-regulated kinase (ERK) and ΔFosB in emotion-associated neural circuitry after asymptotic levels of active avoidance behavior are attained.

Avoidance susceptibility may constitute a vulnerability to develop anxiety disorders, and Wistar-Kyoto (WKY) rats exhibit unique features in their acquisition of avoidance behavior that appear to promote susceptibility to this form of learning, namely the absence of the commonly observed "warm-up" effect. The present study sought to determine if strain differences in acquired avoidance behavior, between WKY and Sprague Dawley rats, could be attributed to differences in dopamine-related plasticity, represented by extracellular signal-regulated kinase (ERK) activity, and prolonged neuronal activation, represented by ΔFosB accumulation, in three key areas of the brain: the medial prefrontal cortex (mPFC), dorsal striatum (DS), and basolateral amygdala (BLA). Consistent with earlier work, WKY rats exhibited a higher level of asymptotic performance of avoidance behavior, which included an absence of warm-up in the first few trials of later training sessions, and they exhibited more non-reinforced anticipatory responses in the single minute prior to the initiation of the first warning signal presentation of each training session.

MLL histone methylases regulate expression of HDLR-SR-B1 in presence of estrogen and control plasma cholesterol in vivo.

High-density lipoprotein receptors scavenger receptor class B type I [HDLR-SR-B1 (SR-B1)] is a key player in reverse cholesterol transport and maintaining blood cholesterol. We demonstrated that human SR-B1 is transcriptionally activated by 17β-estradiol (E2) in HEPG2 and JAR cells. SR-B1 promoter contains multiple estrogen response elements (ERE half-sites) along with some Sp1 binding sites.

Assessing learned associations between conditioned cocaine reward and environmental stimuli in the Wistar Kyoto rat.

Clinical studies demonstrate that anxiety disorders increase the risk of substance use disorder. However, few studies have directly assessed anxiety as a vulnerability factor in processing of rewarding stimuli. The Wistar–Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability because it exhibits extreme behavioral inhibition in novel and social environments; yet, it displays paradoxical rapid active avoidance learning that is resistant to extinction.

Evaluating underlying neuronal activity associated with escape/avoidance behavior in response to noxious stimulation in adult rats.

The place escape/avoidance paradigm (PEAP) is a behavioral test designed to quantify the level of unpleasantness evoked by painful stimuli by assessing the willingness of a subject to escape/avoid a preferred area when it is associated with noxious stimulation. Previous studies have demonstrated that escape/avoidance behavior is dependent on activity in the anterior cingulate cortex (ACC), a region of the limbic system involved in processing the emotional component of pain in humans and animals. Analysis of c-Fos expression in the ACC confirmed that the escape/avoidance response to noxious stimuli corresponds to changes in neural activation in this region.

Influence of sex on reinstatement of cocaine-conditioned place preference.

To explore sex differences in reinstatement of conditioned place preference, we subjected intact male and female Long Evans rats to an extended conditioned place preference (CPP) paradigm, which included observations of acquisition, extinction, and reinstatement of a preference to cocaine-paired stimuli. In a series of experiments, separate groups of animals were given six 30-min pairings of one chamber with cocaine (3, 5, 10, 15, 20, 25mg/kg) and six of the other with saline on alternate days. Overall, there were no sex differences in acquisition of cocaine CPP at any of the six doses tested (p>0.

Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward.

Although chronic cocaine-induced changes in dendritic spines on nucleus accumbens (NAc) neurons have been correlated with behavioral sensitization, the molecular pathways governing these structural changes, and their resulting behavioral effects, are poorly understood. The transcription factor, nuclear factor kappa B (NFkappaB), is rapidly activated by diverse stimuli and regulates expression of many genes known to maintain cell structure. Therefore, we evaluated the role of NFkappaB in regulating cocaine-induced dendritic spine changes on medium spiny neurons of the NAc and the rewarding effects of cocaine.

The influence of DeltaFosB in the nucleus accumbens on natural reward-related behavior.

The transcription factor deltaFosB (DeltaFosB), induced in nucleus accumbens (NAc) by chronic exposure to drugs of abuse, has been shown to mediate sensitized responses to these drugs. However, less is known about a role for DeltaFosB in regulating responses to natural rewards. Here, we demonstrate that two powerful natural reward behaviors, sucrose drinking and sexual behavior, increase levels of DeltaFosB in the NAc.