John C. Heath

Applications of Animal Biosensors: A Review

Odorous compounds perceived by humans or animal species produce a response in chemical- or electronic-based analytical detection systems (chemical sensors, electronic noses, gas chromatography, mass spectrometers, and so on). Animal noses can also produce a recognizable behavioral response in the animal, when exposed to those compounds. Recently, much attention has been paid to the use of animals for scent detection based on their behavioral responses, referred to as animal biosensors. So far, behavioral odor detection by animals has been applicable in some fields, such as forensic sciences, homeland security, or, more recently, cancer diagnostics. The major advantage of animal biosensors is that the animals can be conditioned rapidly and cost-effectively, offering benefits in terms of noninvasive detection and early diagnosis. Here, we review the applications of living biosensors as whole animal biosensors and discuss the main issues, approaches, and challenges.

Response inhibition is impaired by developmental methylmercury exposure: Acquisition of low-rate lever-pressing ☆

Developmental methylmercury (MeHg) exposure produces response perseveration on discrimination reversal procedures, disrupts sensitivity to reinforcement, and enhances sensitivity to dopamine agonists - a profile suggesting a deficit in behavioral inhibition. To examine inhibition, we examined MeHgs effects on the acquisition and persistence of low-rate lever-pressing following a history of high-rate responding. Additionally, we examined whether chronic exposure to selenium protects against MeHgs developmental neurotoxicity. Female rats were exposed in utero via maternal exposure to drinking water containing 0ppm, 0.5ppm or 5ppm of Hg as MeHg, producing approximately 0μg/kg/day, 40μg/kg/day, or 400μg/kg/day of Hg. The mothers (during gestation) and the offspring (throughout life) consumed a purified diet containing 0.06ppm or 0.6ppm of Se (as sodium selenite), forming a 2 (lifespan diet)×3 (developmental MeHg) factorial design. Adult offspring lever-pressed under two schedules of reinforcement. A differential reinforcement of high-rate (DRH) schedule imposed rigid response requirements that remained constant through the study. A high-rate percentile schedule (PCNT-H) incorporated a flexible criterion that reinforced short interresponse times using an adjusting criterion that was sensitive to recent performance. After high-rate responding stabilized, the PCNT-H schedule was abruptly inverted by reinforcing long interresponse times. Acquisition of low-rate responding was impaired in the MeHg-exposed rats because of intrusions of high-rate response bursts. DRH response rates did not change. Dietary selenium did not influence MeHgs effects. High-rate operant behavior perseverated, suggesting that gestational MeHg exposure impairs response inhibition - an effect that extends results previously reported using choice procedures or spatial and visual discrimination reversals.

The Effects of Chronic Ingestion of Mercuric Chloride on Fertility and Testosterone Levels in Male Sprague Dawley Rats

Although male infertility is well researched, the effects of inorganic mercury on male reproduction and fertility are less well known. Studies pertaining to mercury and male fertility identified reduced concentration of testosterone in the serum of male workers, a toxic influence on fertility of organic mercury compounds within concentrations at the workplace, and increased days to pregnancy. We evaluated the effect of chronic mercuric chloride (HgCl2) exposure in male rats on reproductive endpoints. Thirty-day old male Sprague Dawley rats (n = 31) were exposed to 0.0, 1.0, or 2.0 mg/kg/day of HgCl2 via gavage. After 60 days exposure, they were housed with nonexposed females for 21 days. A survivor analysis revealed the exposed animals took longer to impregnate the females and had a lower rate of impregnation. Further statistical analysis revealed a lower correlation between testicular testosterone levels and days to impregnate, and also lower sperm counts in the epididymis head and body of the exposed males. The results indicate that HgCl2 exposure had significant adverse effects on male rat reproduction endpoints including fertility at a dose that was not clinically toxic.

The effects of chronic mercuric chloride ingestion in female Sprague-Dawley rats on fertility and reproduction.

Thirty-days-old female rats were chronically exposed, for 60 days, to 1or 2mg/kg/day of mercuric chloride or an equivalent volume of water, via gavage. At 90 days of age they were mated with unexposed males. At approximately day 13 of gestation necropsies were performed on the females. Data were collected on the number of implantations and non-viable implantations in the uterus. No physical signs of Hg intoxication were seen except in weight gain. There were significantly fewer implantations in the high HgCl2 group, with significantly more non-viable implantations in the low and high HgCl2 groups, compared to controls. Lower levels of progesterone and higher levels of pituitary luteinizing hormone (LH) were found in the high HgCl2 group compared to controls, whereas pituitary follicle stimulating hormone levels (FSH), while not significant, showed a dose-response relationship to HgCl2 levels. No difference was found in the number of corpora lutea. The experiment indicated low level chronic ingestion of mercuric chloride, in female rats, while not effecting ovulation, produced disruption of implantation and fetal viability. Lower progesterone levels, higher LH, and possibly FSH levels, indicate that mercuric chloride may have a disruptive effect in the corpora lutea which manifests itself after ovulation.

Genetically induced estrogen receptor α mRNA (Esr1) overexpression does not adversely affect fertility or penile development in male mice.

Previously, we reported that estrogen receptor α mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and maldeveloped penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < .05) lower as compared with controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, genetically induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except for limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles.

Exogenous glucagon-like peptide-1 reduces body weight and cholecystokinin-8 enhances this reduction in diet-induced obese male rats

The sites of action regulating meal size (MS) and intermeal interval (IMI) length by glucagon like peptide-1 (7-36) (GLP-1 (7-36)) and cholecystokinin-8 (CCK-8) reside in the areas supplied by the two major branches of the abdominal aorta, celiac and cranial mesenteric arteries. We hypothesized that infusing GLP-1 near those sites reduces body weight (BW) and adding CCK-8 to this infusion enhances the reduction. Here, we measured BW in diet-induced obese (DIO) male rats maintained and tested on normal rat chow and infused with saline, GLP-1 (0.5nmol/kg) and GLP-1+CCK-8 (0.5nmol/kg each) in the aorta once daily for 21days. We found that GLP-1 and GLP-1+CCK-8 decrease BW relative to saline vehicle and GLP-1+CCK-8 reduced it more than GLP-1 alone. Reduction of BW by GLP-1 alone was accompanied by decreased 24-h food intake, first MS, duration of first meal and number of meals, and an increase in latency to first meal. Reduction of BW by the combination of the peptides was accompanied by decrease 24-h food intake, first MS, duration of first meal and number of meals, and increase in the IMI length, satiety ratio and latency to first meal. In conclusion, GLP-1 reduces BW and CCK-8 enhances this reduction if the peptides are given near their sites of action.

Combined gastrin releasing peptide-29 and glucagon like peptide-1 reduce body weight more than each individual peptide in diet-induced obese male rats

To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than each of the peptides given individually, we infused the two peptides (0.5nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25days and measured BW. We found that GRP-29 and GLP-1 reduce BW, GRP-29 reduced it more than GLP-1 and GRP-29+GLP-1 reduce BW more than each peptide given alone. This reduction was accompanied by decrease 24-hour food intake (normal rat chow), meal size (MS), duration of first meal and number of meals, and increase latency to the first meal, intermeal interval (IMI) and satiety ratio (IMI/MS, amount of food consumed per a unit of time). Furthermore, the peptides and their combination decreased 24-hour glucose levels. In conclusion, GRP-29+GLP-1 reduce BW more than each of the peptides given individually.