Although beneficial effects have been attributed to PUFA supplementation in high-yielding dairy cows, diets rich in PUFA may also increase oxidative stress in tissues such as the liver. To fully exploit the health benefits of PUFA, we believe that the addition of natural antioxidants could help in preventing oxidative damage. Using an in vitro precision-cut liver slices (PCLS) tissue culture system, we investigated the effects of different linoleic acid (LA, n-6):α-linolenic acid (ALA, n-3) ratios (LA:ALA ratio of 4, LA:ALA ratio of 15 and LA:ALA ratio of 25) in the presence or absence of the antioxidant enterolactone (ENL) on (1) the mRNA abundance of genes with key roles in hepatic lipid metabolism, oxidative stress response and inflammatory processes, (2) oxidative damages to lipids and proteins and (3) superoxide dismutase activity in early-lactating dairy cows. The addition of LA and ALA to PCLS culture media increased oxidative damage to lipids as suggested by higher concentrations of thiobarbituric acid reactive substances and increased the expression of nuclear factor erythroid 2-related factor 2 target genes. The addition of ENL was effective in preventing lipid peroxidation caused by LA and ALA. Transcript abundance of sterol regulatory element-binding transcription factor 1 and its lipogenic target genes acetyl-CoA carboxylase α, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) was decreased with LA and ALA, whereas ENL decreased FASN and SCD gene expression. Our results show that addition of LA and ALA to PCLS culture media lowers hepatic lipogenic gene expression and increases oxidative damages to lipids. On the other hand, addition of ENL prevents oxidative damages provoked by these PUFA.
Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically foodrestricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.
Drug addiction is a chronic disorder that is characterized by compulsive drug seeking and involves cycling between periods of compulsive drug use, abstinence, and relapse.In both human addicts and animal models of addiction, chronic food restriction has been shown to increase rates of relapse. Previously, our laboratory has demonstrated a robust increase in drug seeking following a period of withdrawal in chronically foodrestricted rats compared with sated rats. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug seeking have not been elucidated. However, the paraventricular nucleus of the thalamus (PVT) appears to be a promising target to investigate. The objective of the current study was to examine the role of the PVT in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 days. Rats were then removed from the training chambers and experienced a 14-day withdrawal period with either unrestricted (sated) or mildly restricted (FDR) access to food. On day 14, rats underwent a 1-hour heroin-seeking test under extinction conditions, during which neural activity in the PVT was either inhibited or increased using pharmacological or chemogenetic approaches. Unexpectedly, inhibition of the PVT did not alter heroin seeking in food-restricted or sated rats, while enhancing neural activity in the PVT-attenuated heroin seeking in food-restricted rats. These results indicate that PVT activity can modulate heroin seeking induced by chronic food restriction.
Potential links between measures of udder morphology obtained in live pregnant gilts and mammary gland development and composition measured in mammary tissue collected at slaughter were studied. Thirty-three gilts were used. In vivo measures of gland morphology using a tape or ultrasound imaging (parenchymal area measured by ultrasound [AREA]) were obtained on d 108 ± 1 of gestation. Gilts were then slaughtered on d 110 ± 1 of gestation to collect mammary glands for dissection and compositional analyses. The various tape measures were the distance between each teat on one side of the udder (DIST-TEAT), the distance between each teat pair (DIST-PAIR), the length of the udder (sum of all DIST-TEAT), the distance between the base of the teat and the ventral midline section of the udder (MID), and the distance between the base of the teat and the exterior junction of the udder with the abdomen (EXT). The variables MID, DIST-TEAT, DIST-PAIR, and length had very poor correlations with parenchymal weight, extraparenchymal weight, or any of the measured compositional variables. On the other hand, both AREA and EXT were correlated ( < 0.01) with the weight of parenchymal tissue, total parenchymal protein, total DNA, and total RNA. The ultrasound measure AREA and the tape measure EXT were also correlated with each other ( < 0.05). These measures could, therefore, be helpful to estimate mammary development in studies where animals cannot be slaughtered. The tape measure EXT seemed to better reflect the volume of the gland than MID, and it provided as reliable an estimate of parenchymal weight as the measure of parenchymal area using ultrasound while being much easier and cheaper to obtain.
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