Maternal Flavonoids Intake Reverts Depression-Like Behaviour in Rat Female Offspring.

Maternal hypercaloric exposure during pregnancy and lactation is a risk factor for developing diseases associated with inflammation such as obesity, diabetes and, neurological diseases in the offspring. Neuroinflammation might modulate neuronal activation and flavonoids are dietary compounds that have been proven to exert anti-inflammatory properties. Thus, the aim of the present study is to evaluate the effect of maternal supplementation with flavonoids (kaempferol-3-O-glucoside and narirutin) on the prevention of depression-like behaviour in the female offspring of dams fed with an obesogenic diet during the perinatal period. Maternal programming was induced by high fat (HFD), high sugar (HSD), or cafeteria diets exposure and depressive like-behaviour, referred to as swimming, climbing, and immobility events, was evaluated around postnatal day 56⁻60 before and after 30 mg/kg i.p. imipramine administration in the female offspring groups. Central inflammation was analyzed by measuring the TANK binding kinase 1 (TBK1) expression. We found that the offspring of mothers exposed to HSD programming failed to show the expected antidepressant effect of imipramine. Also, imipramine injection, to the offspring of mothers exposed to cafeteria diet, displayed a pro-depressive like-behaviour phenotype. However, dietary supplementation with flavonoids reverted the depression-like behaviour in the female offspring. Finally, we found that HSD programming increases the TBK1 inflammatory protein marker in the hippocampus. Our data suggest that maternal HSD programming disrupts the antidepressant effect of imipramine whereas cafeteria diet exposure leads to depressive-like behaviour in female offspring, which is reverted by maternal flavonoid supplementation.

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring.

BACKGROUND: Maternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning. METHODS: We exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192. RESULTS: Maternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca2+ overload into mitochondria matrix leading to mitochondrial dysfunction. CONCLUSIONS: We concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux.

Obesogenic diet intake during pregnancy programs aberrant synaptic plasticity and addiction-like behavior to a palatable food in offspring.

Contextual food conditioned behaviors require plasticity of glutamatergic neurotransmission in the reward system, involving changes in the expression of including a-amino-3-hydroxy-5-methylisoxazole 4-propionate receptors (AMPA), N-methyl-d-aspartic acid (NMDA) and metabotropic glutamate 2,3 (mGlur 2,3). However, the role of changes in glutamatergic synaptic markers on energy-dense palatable food preference during development has not been described. Here, we determine the effect of nutritional programing during gestation on fat food choices using a conditioned place preference (CPP) test and an operant training response and its effect on glutamatergic markers in the nucleus accumbens (Nac) shell and prefrontal cortex (PFC). Our data showed that rats displayed preference for palatable fat food and an increase in caloric intake when compared to a chow diet. Notably, 74% of rats showing a preference for fat food intake correlate with a positive HFD-paired score whereas 26% failed to get HFD-conditioned. Also, male rats trained under an operant training response schedule (FR1, FR5 and PR) showed high and low responder groups to work for food. Notably, hypercaloric nutritional programing of female rats leads to exacerbation for reinforcers in female offspring compared to offspring from chow diet. Finally, we found that an operant training response to palatable reinforcers correlates with upregulation of mGlur 2,3 in the NAc shell and PFC of male rats and female offspring. Also, we found selective Nr1 upregulation in NAc shell and the PFC of female offspring. Our data suggest that nutritional programing by hypercaloric intake leads to incentive motivation to work for food and synaptic plasticity alteration in the mesolimbic system.

Noninvasive measurement of blood pressure variability: accuracy of the Finometer monitor and comparison with the Finapres device.

To assess the accuracy of spectral indices of arterial pressure variability and baroreflex sensitivity obtained from beat-by-beat noninvasive blood pressure recordings by the Finometer device, we compared these measures with those obtained from intra-arterial recordings. The performance of the Finometer was also compared to the traditional Finapres device. In 19 cardiac disease patients, including myocardial infarction, heart failure and cardiac transplant, we estimated the power of systolic and diastolic pressures in the VLF (0.01-0.04 Hz), LF (0.04-0.15 Hz) and HF (0.15-0.45 Hz) bands and computed absolute and percentage errors relative to intra-arterial brachial pressure. We also computed the characteristic frequency of each band (i.e. the barycentric frequency of spectral components identified in the band). The variability of systolic pressure in the VLF and LF bands was markedly overestimated by both the Finometer and Finapres (p < 0.01), with percentage median errors of respectively 130% and 103% (Finometer), and 134% and 78% (Finapres). The HF power was substantially unchanged using the Finometer and reduced using the Finapres (-28%, p < 0.05). The limits of agreement between noninvasive and invasive spectral measurements were wide. Linear system analysis showed that most (>80%) of the power of noninvasive signals was linearly related to the power of the invasive signal. The characteristic frequency of each band was substantially preserved in both noninvasive signals. The results for diastolic pressure were similar, but the Finapres errors in the VLF and LF bands were lower. Baroreflex sensitivity was significantly underestimated by both devices (Finometer: -31%, Finapres: -24%). Despite previous studies having shown that brachial artery waveform reconstruction performed by the Finometer has improved the accuracy of blood pressure measurement compared to the Finapres device, measurement of blood pressure variability in cardiac disease patients provides worse results in most spectral parameters and a better accuracy only in the HF band of systolic pressure.

RESP-24: a computer program for the investigation of 24-h breathing abnormalities in heart failure patients.

In this paper, we describe a computer program (RESP-24) specifically devised to assess the prevalence and characteristics of breathing disorders in ambulant chronic heart failure patients during the overall 24 h period. The system works on a single channel respiratory signal (RS) recorded through a Holter-like portable device. In the pre-processing stage RESP-24 removes noise, baseline drift and motion artefacts from the RS using a non-linear filter, enhances respiratory frequency components through high-pass filtering and derives an instantaneous tidal volume (ITV) signal. The core processing is devoted to the identification and classification of the breathing pattern into periodic breathing (PB), normal breathing or non-classifiable breathing using a 60 s segmentation, and to the identification and estimation of apnea and hypopnea events. Sustained episodes of PB are detected by cross analysis of both the spectral content and time behavior of the ITV signal. User-friendly interactive facilities allow all the results of the automatic analysis procedure to be edited. The final report provides a set of standard and non-standard parameters quantifying breathing abnormalities during the 24 h period, the night-time and the day-time, including the apnea/hypopnea index, the apnea index, the total time spent in apnea or in hypopnea and the prevalence of non-apneic and apneic PB. The accuracy of these measurements was appraised on a data set of 14 recordings, by comparing them with those provided by a trained analyst. The mean and standard deviation of the error of the automatic procedure were below respectively 6 and 8% of the reference value for all parameters considered and the mean total classification accuracy was 92%. In most cases, the individual error was <12%. We conclude that measurements provided automatically by the RESP-24 software are suitable for screening purposes and clinical trials, although a preventive check of signal quality should be recommended.