Early-Life Exposure to Cadmium Triggers Distinct Zn-Dependent Protein Expression Patterns and Impairs Brain Development

Abstract The endocrine disrupting compound bisphenol-A (BPA) has been reported to act as an obesogen in rodents exposed perinatally. In this study, we investigated the effects of early-life BPA exposure on adult metabolic phenotype and hypothalamic energy balance circuitry. Pregnant and lactating CD-1 dams were exposed, via specially prepared diets, to 2 environmentally relevant doses of BPA. Dams consumed an average of 0.19 and 3.49 μg/kg per day of BPA in the low and high BPA treatments prenatally and an average of 0.36 and 7.2 μg/kg per day of BPA postnatally. Offspring were weaned initially onto a normal (AIN93G) diet, then as adults exposed to either a normal or high-fat diet (HFD). Males exposed to the high dose of BPA showed impaired glucose tolerance on both diets. They also showed reduced proopiomelanocortin fiber innervation into the paraventricular nucleus of the hypothalamus, and when exposed to HFD, they demonstrated increased neuropeptide Y and Agouti-related peptide expression in the arcuate nucleus (ARC). Females exposed to the high BPA dose were heavier, ate more, and had increased adiposity and leptin concentrations with reduced proopiomelanocortin mRNA expression in the ARC when consuming a HFD. BPA-exposed females showed ARC estrogen receptor α expression patterns similar to those seen in males, suggesting a masculinizing effect of BPA. These results demonstrate that early-life exposure to the obesogen BPA leads to sexually dimorphic alterations in the structure of hypothalamic energy balance circuitry, leading to increased vulnerability for developing diet-induced obesity and metabolic impairments, such as glucose intolerance.

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Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens

Communications Biology ◽

10.1038/s42003-021-02358-w ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Alberto J. López ◽

Amy R. Johnson ◽

Tanner J. Euston ◽

Rashaun Wilson ◽

Suzanne O. Nolan ◽

...

Keyword(s):

Nucleus Accumbens ◽

Protein Expression ◽

Drugs Of Abuse ◽

Expression Patterns ◽

Neural Function ◽

Self Administration ◽

Drug Induced ◽

Dependent Protein ◽

Males And Females ◽

Molecular Substrates

AbstractSubstance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates that underlie these persistent changes in neural function and behavior. However, this work has overwhelmingly focused on male subjects, despite mounting clinical and preclinical evidence that females demonstrate dissimilar progression to SUD and responsivity to stimulant drugs of abuse, such as cocaine. Here, we show that sex is a critical biological variable that defines drug-induced plasticity in the nucleus accumbens (NAc). Using quantitative mass spectrometry, we assessed the protein expression patterns induced by cocaine self-administration and demonstrated unique molecular profiles between males and females. We show that 1. Cocaine self-administration induces non-overlapping protein expression patterns in significantly regulated proteins in males and females and 2. Critically, cocaine-induced protein regulation differentially interacts with sex to eliminate basal sexual dimorphisms in the proteome. Finally, eliminating these baseline differences in the proteome is concomitant with the elimination of sex differences in behavior for non-drug rewards. Together, these data suggest that cocaine administration is capable of rewriting basal proteomic function and reward-associated behaviors.

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Bone-specific gene expression patterns and whole bone tissue of female mice are programmed by early life exposure to soy isoflavones and folic acid

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2015.04.013 ◽

2015 ◽

Vol 26 (10) ◽

pp. 1068-1076 ◽

Cited By ~ 12

Author(s):

Jovana Kaludjerovic ◽

Wendy E. Ward

Keyword(s):

Gene Expression ◽

Folic Acid ◽

Bone Tissue ◽

Early Life ◽

Expression Patterns ◽

Soy Isoflavones ◽

Gene Expression Patterns ◽

Specific Gene ◽

Female Mice ◽

Early Life Exposure

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Effects of early life exposure to traffic-related air pollution on brain development in juvenile Sprague-Dawley rats

Translational Psychiatry ◽

10.1038/s41398-020-0845-3 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Kelley T. Patten ◽

Eduardo A. González ◽

Anthony Valenzuela ◽

Elizabeth Berg ◽

Christopher Wallis ◽

...

Keyword(s):

Air Pollution ◽

Brain Development ◽

Early Life ◽

Sprague Dawley ◽

Early Life Exposure ◽

Sprague Dawley Rats

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Chemically Contaminated Eel Fed to Pregnant and Lactating Mouse Dams Causes Hyperactivity in Their Offspring

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000288 ◽

2016 ◽

Vol 86 (1-2) ◽

pp. 36-47 ◽

Cited By ~ 2

Author(s):

Imen Dridi ◽

Nidhal Soualeh ◽

Torsten Bohn ◽

Rachid Soulimani ◽

Jaouad Bouayed

Keyword(s):

Open Field ◽

Early Life ◽

Home Cage ◽

Anguilla Anguilla ◽

Acetylcholinesterase Activity ◽

Female Offspring ◽

Significant Inhibition ◽

Standard Diet ◽

Early Life Exposure ◽

Cage Test

Abstract.This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 – 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 – 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.

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