Differential Effect of Fat Intake on Blood Pressure in Healthy Japanese Women with and without the Variant of Fat Mass and Obesity-Associated Gene.

A high-fat diet is believed to be a risk factor for hypertension through inducing obesity. It has been reported that variants of the fat mass and obesity-associated (FTO) and beta-3 adrenergic receptor (B3AR) genes are associated with obesity and blood pressure. The purpose of this study was to investigate the effect of dietary fat on blood pressure with or without the variant of the FTO and B3AR genes. A total of 227 healthy Japanese women aged 18 to 64 years were recruited for measurement of nutrient intake and blood pressure. The single nucleotide polymorphism rs9939609 of the FTO gene and rs4994 of the B3AR gene were genotyped. Spearman's rank correlation coefficient was applied to investigate the relationship between fat intake and blood pressure. A hierarchical multiple regression analysis was performed to determine whether the genotype interacts with fat intake to affect blood pressure. No significant correlations were found between fat intake and either systolic or diastolic blood pressure. A significant negative correlation was found between fat intake and both blood pressures in the FTO-gene-variant group, but not in the normal-FTO-gene group. In hierarchical multiple regression analysis, the interaction of fat intake and the gene variant showed significance, and the change in coefficient of determination (R 2) was significantly increased with increases of the interaction variable. These results indicate that the effect of fat intake on blood pressure may be modified by the variant of the FTO gene such that a high-fat diet intake may be associated with a decrease of systolic and diastolic blood pressure in healthy Japanese women with the FTO variant. Our results did not support the hypothesis that a high-fat diet increases blood pressure.

Supplementation with trans fatty acid at 1% energy did not increase serum cholesterol irrespective of the obesity-related genotypes in healthy adult Japanese.

BACKGROUND AND OBJECTIVES: The excessive intake of trans fatty acids increases serum low-density lipoproteincholesterol and reduces high-density lipoprotein-cholesterol. We studied the effects of 1% energy trans fatty acid supplementation on serum lipid concentrations in healthy adult Japanese with different obesity-related gene polymorphisms. METHODS AND STUDY DESIGN: A randomized, double-blind, parallel trial was conducted in 53 healthy adults. The volunteers consumed one cookie containing either 1% energy or <0.01% energy (control) of trans fatty acids every day for 4 weeks, and a blood sample was then obtained after overnight fasting. The single nucleotide polymorphisms of the fat mass- and obesity-associated gene rs9939609 and beta-3 adrenergic receptor rs4994 were genotyped. RESULTS: The mean trans fatty acid intake of the control and trans fatty acid groups corresponded to 0.28% and 1.31 % energy, respectively. There were no significant differences in serum cholesterol (total, low-density lipoprotein and high-density lipoprotein) or triacylglycerol between the control and trans fatty acid groups. The responses of serum cholesterol, triacylglycerol, glucose, insulin and hemoglobinA1c were also independent of the fat mass- and obesity-associated gene and beta-3 adrenergic receptor gene variants. CONCLUSIONS: Our findings indicate that supplementation with 1% energy trans fatty acids has little effect on serum cholesterol in healthy adult Japanese, regardless of genotype of fat mass- and obesity-associated gene or beta-3 adrenergic receptor. More systematic studies, with respect to dietary trans fatty acid intakes above those used here, may be warranted to determine the tolerable upper level of dietary trans fatty acid.

Little Effect of Supplementation with 0.6% Energy Trans Fatty Acids on Serum Cholesterol Levels in Adult Japanese Women.

The excessive intake of trans fatty acids (TFAs) increases serum LDL-cholesterol and reduces HDL-cholesterol. Limited data exist regarding the low-level intake of TFAs, and the tolerable upper-limit level remains to be fully elucidated. A randomized, double-blind, parallel trial was conducted to assess the effects of a low level of TFA supplementation on serum cholesterol levels in healthy adult Japanese women. The volunteers who participated in this examination took in approximately 0.4% of energy (%E) TFAs from daily meals. Fifty-one volunteers consumed one cookie containing 0.6%E (TFA) or 0.04%E (control) of TFAs every day for 4 wk, and blood was harvested after overnight fasting. The mean TFA intakes of the control and TFA groups during the experimental period were 0.4%E and 1.1%E, respectively. There were no significant differences in serum total, LDL- or HDL-cholesterol levels between the control and TFA groups. The serum glucose and insulin levels were not influenced by TFA supplementation. These results confirm that dietary supplementation with 0.6%E TFAs (a total TFA intake of approximately 1%E) would have little effect on serum cholesterol levels in healthy adult Japanese women.

Trans fatty acid intake and serum cholesterol levels in young Japanese women.

There are very limited data concerning the influence of low-level trans fatty acid (TFA) intake on blood lipid levels. In this study, correlation of total and diene TFA intake with serum cholesterol levels was studied in young Japanese women. The mean intakes of total and diene TFAs were 0.36% and 0.05% of energy, respectively. There was a significant correlation between total fat intake and TFA intake. TFA intake was significantly correlated with erythrocyte TFA content. Total TFA intake was not correlated with total, LDL- or HDL-cholesterol levels. No correlatuon was found between diene TFA intake and cholesterol level. Total and diene TFA intake were not correlated with hemoglobin A1c or C-reactive protein levels. These results suggest that the average TFA intake of young Japanese women does not adversely affect serum cholesterol levels.

Effect of a 0.6% energy trans fatty acid intake on serum cholesterol concentrations in healthy young Japanese subjects.

A randomized crossover study in healthy young Japanese showed no significant effects of a 0.6% energy trans fatty acid (TFA) intake on the serum cholesterol concentrations and parameters of glucose metabolism. The results indicate that TFAs at this dietary level may have no adverse metabolic effects on healthy young Japanese.

Task-dependent and independent synchronous activity of monkey hippocampal neurons in real and virtual translocation.

Previous neurophysiological and behavioral studies relate hippocampal functions to place learning and memory, and encoding of task (or context)-specific information. Encoding of both task-specific information and own location is essential for episodic memory and for animals to navigate to reward-related places. It is suggested that different neural circuits with different assemblies of different hippocampal neurons are created in different environments or behavioral contexts for the hippocampal formation (HF) to encode and retrieve episodic memory. To investigate whether synchronous activity of hippocampal neurons, suggesting functional connectivity between those neurons, is task and position dependent, multiple single unit activities were recorded during performance of real and virtual translocation (VT) tasks. The monkey moved to one of four reward areas by driving a cab (real translocation) or by moving a pointer on a monitor. Of 163 neuron pairs, significant peaks in cross-correlograms (CCGs) were observed in 98 pairs. Most CCGs had positive peaks within 50 ms. Task-dependent cross-correlations (CCRs) were observed in 44% of the neuron pairs, and similarly observed in both the real and VT tasks. These CCRs were frequently observed in pyramidal vs. pyramidal neuron pairs with positive peak and peak shift. However, no consistent patterns of peak polarity, peak shift, and neuronal types were seen in task-independent CCRs. There was no significant difference in frequency of CCG peaks between real and VT tasks. These results suggest that the task-dependent information may be encoded by interaction among pyramidal neurons, and the common information across tasks may be encoded by interaction among pyramidal neurons and interneurons in the HF. These neuronal populations could provide a neural basis for episodic memory to disambiguously guide animals to places associated with reward in different situations.

Anticipatory reward signals in ventral striatal neurons of behaving rats.

It has been proposed that the striatum plays a crucial role in learning to select appropriate actions, optimizing rewards according to the principles of 'Actor-Critic' models of trial-and-error learning. The ventral striatum (VS), as Critic, would employ a temporal difference (TD) learning algorithm to predict rewards and drive dopaminergic neurons. This study examined this model's adequacy for VS responses to multiple rewards in rats. The respective arms of a plus-maze provided rewards of varying magnitudes; multiple rewards were provided at 1-s intervals while the rat stood still. Neurons discharged phasically prior to each reward, during both initial approach and immobile waiting, demonstrating that this signal is predictive and not simply motor-related. In different neurons, responses could be greater for early, middle or late droplets in the sequence. Strikingly, this activity often reappeared after the final reward, as if in anticipation of yet another. In contrast, previous TD learning models show decremental reward-prediction profiles during reward consumption due to a temporal-order signal introduced to reproduce accurate timing in dopaminergic reward-prediction error signals. To resolve this inconsistency in a biologically plausible manner, we adapted the TD learning model such that input information is nonhomogeneously distributed among different neurons. By suppressing reward temporal-order signals and varying richness of spatial and visual input information, the model reproduced the experimental data. This validates the feasibility of a TD-learning architecture where different groups of neurons participate in solving the task based on varied input information.

[Influence of malalignment and malocclusion on mental and physical health-consciousness in senior high school students].

OBJECTIVES: Dental examinations and a questionnaire survey were carried out simultaneously in senior high schools to investigate influence of tooth misalignment and malocclusion on mental and physical health-consciousness of the students. METHODS: The questionnaire survey concerning health-consciousness was collected after the dental examination. The students were divided into three groups by their findings: "within a normal range"; "mild-", and "severe- misalignment and malocclusion". The relationship between the severity of dental abnormality and mental and physical status in health by the questionnaire survey was studied. RESULTS: The severity of misalignment and malocclusion correlated with (1) degree of consciousness of irregular teeth, and (2) degree of negative evaluation of themselves for their health-consciousness. CONCLUSION: There is possibility that the severity of misalignment and malocclusion corresponds to a negative self evaluation and causes mental stress. It is suggested that it is very important to identify young people with such problems at an early stage, and then to consult and promote correct dental alignment and occlusion, providing not only sufficient mastication but also unhampered mental development.

Place-related neural responses in the monkey hippocampal formation in a virtual space.

Place cells in the rodent hippocampal formation (HF) are suggested to be the neural substrate for a spatial cognitive map. This specific spatial property of the place cells are regulated by both allothetic cues (i.e., intramaze local and distal cues) as well as idiothetic sensory inputs; the context signaled by the distal cues allows local and idiothetic cues to be employed for spatial tuning within the maze. To investigate the effects of distal cues on place-related activity of primate HF neurons, 228 neurons were recorded from the monkey HF during virtual navigation in a similar situation to a rodent water maze, in which distal cues were important to locate the animal's position. A subset of 72 neurons displayed place-related activity in one or more virtual spaces. Most place-related responses disappeared or changed their spatial tuning (i.e., remapping) when the arrangements of the distal cues were altered/moved in the virtual spaces. These specific features of the monkey HF might underlie neurophysiological bases of human episodic memory.

Neural correlates to action and rewards in the rat posterior cingulate cortex.

To investigate the involvement of the posterior cingulate cortex in reward-based learned actions, we examined its neuronal activities in rats that were trained in a delayed stimulus-response association task. Of the 344 neurons recorded, 178 responded during licking a spout to acquire rewards (a sucrose solution or intracranial self-stimulation). Of these 178 reward-responsive neurons, 80 responded exclusively during licking to acquire sucrose solution, and 20 during licking to acquire intracranial self-stimulation, with 37 of these 100 neurons displaying differential correlation to individual licking on the basis of the reward type. The present results and comparison with previous studies on the anterior cingulate cortex suggest that the posterior cingulate cortex is involved in the monitoring or storage of action-reward outcome association.

Effects of prenatal maternal stress by repeated cold environment on behavioral and emotional development in the rat offspring.

It has been reported that many types of stresses, which caused physiological and psychological alterations in dams as prenatal maternal stress, affected behavioral and emotional traits of their offspring. However, effects of environmental temperature changes, which induce various stress responses in both animals and humans, have not been assessed as prenatal maternal stress. Repeated cold stress (RCS) is a type of chronic cold stress in which environmental temperature changes rapidly and frequently several times within a day. In the present study, to investigate effects of chronic maternal stress by the RCS on behavioral and emotional development of the rat offspring (prenatal RCS rats), the RCS stress was loaded to pregnant rats between day 9 and 19 after fertilization. The prenatal RCS rats showed similar locomotor activity in an open field to control rats that were borne by non-stressed pregnant rats. On the other hand, the prenatal RCS rats showed significantly higher startle responses than the control rats in a light enhanced startle paradigm. However, treatment of diazepam decreased the startle responses in the prenatal RCS rats to the same degree as those in the control rats. The results indicated that prenatal RCS affected emotional development of the rat offspring, but not locomotor activity. Comparison of the present results with the previous studies suggests that there might be unknown common mechanisms among different prenatal maternal stresses that induce similar behavioral developmental alteration.

Neurons in hippocampal afferent zones of rat striatum parse routes into multi-pace segments during maze navigation.

Hippocampal 'place' neurons discharge when rats occupy specific regions within an environment. This finding is a cornerstone of the theory of the hippocampus as a cognitive map of space. But for navigation, representations of current position must be implemented by signals concerning where to go next, and how to get there. In recordings in hippocampal output structures associated with the motor system (nucleus accumbens and ventromedial caudate nucleus) in rats solving a plus-maze, neurons fired continuously from the moment the rat left one location until it arrived at the next goal site, or at an intermediate place, such as the maze centre. While other studies have shown discharges during reward approach behaviours, this is the first demonstration of activity corresponding to the parsing of complex routes into sequences of movements between landmarks, similar to the lists of instructions we often employ to communicate directions to follow between points on a map. As these cells fired during a series of several paces or re-orientation movements, perhaps this is homologous to 'chunking'. The temporal overlaps in the activity profiles of the individual neurons provide a possible substrate to successively trigger movements required to arrive at the goal. These hippocampally informed, and in some cases, spatially selective responses support the view of the ventral striatum as an interface between limbic and motor systems, permitting contextual representations to have an impact on fundamental action sequences for goal-directed behaviour.

Autonomic responses during inhalation of natural fragrance of Cedrol in humans.

It is well known that odors affect behaviors and autonomic functions. Previous studies reported that some compounds in cedar wood essence induced behavioral changes including sedative effects. In the present study, we analyzed cardiovascular and respiratory functions while subjects were inhaling fumes of pure compound (Cedrol) which was extracted from cedar wood oil. Vaporized Cedrol (14.2+/-1.7 microg/l, 5 l/min) and blank air (5 l/min) were presented to healthy human subjects (n=26) via a face mask, while ECGs, heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), and respiratory rates (RR) were monitored. Statistical analyses indicated that exposure to Cedrol significantly decreased HR, SBP, and DBP compared to blank air while it increased baroreceptor sensitivity. Furthermore, respiratory rate was reduced during exposure to Cedrol. These results, along with the previous studies reporting close relationship between respiratory and cardiovascular functions, suggest that these changes in respiratory functions were consistent with above cardiovascular alterations. Spectral analysis of HR variability indicated an increase in high frequency (HF) component (index of parasympathetic activity), and a decrease in ratio of low frequency to high frequency components (LF/HF) (index of sympathovagal balance) during Cedrol inhalation. Furthermore, Cedrol inhalation significantly decreased LF components of both SBP and DBP variability, which reflected vasomotor sympathetic activity. Taken together, these patterns of changes in the autonomic parameters indicated that Cedrol inhalation induced an increase in parasympathetic activity and a reduction in sympathetic activity, consistent with the idea of a relaxant effect of Cedrol.

Representation of place by monkey hippocampal neurons in real and virtual translocation.

The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place-selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place-selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place-selective responses, into geometric relationships in a two-dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map.

Gamma-band EEGs predict autonomic responses during mental arithmetic.

Relationship between gamma-band (20-80 Hz) EEGs and autonomic functions (heart rate, blood pressure, instantaneous lung flow) in a mental arithmetic task (MAT) were investigated. Subjects were instructed to add 2 integers after presentation of audio voices indicating the integers in the MAT, and to listen to the same voices without mental arithmetic in the control task. The gamma-EEGs and autonomic functions coherently changed in response to the voices before mental arithmetic in the MAT. Furthermore, an increase in gamma-EEGs went ahead of the autonomic fluctuation. The results suggest that the gamma-band activity modulates and adjusts peripheral autonomic functions in advance before actual mental activity. This is the first demonstration that cortical gamma-band activity triggers peripheral autonomic responses during mental activity.

Spatio-temporal dynamics of brain activated regions during drinking behavior in rats.

Spatio-temporal dynamics of activated brain areas induced by drinking were investigated and visualized in behaving rats using functional magnetic resonance imaging (fMRI). The rats were trained to drink in the magnet bore, and the images were taken during and after drinking glucose and distilled water. During glucose ingestion, the signal intensity was increased continuously and maximally in the lateral hypothalamic area (LHA) and the ventromedial hypothalamus (VMH). Somewhat less intense activation in the central nucleus of the amygdala (AMc), and transient activation in the piriform cortex and the mediodorsal nucleus of the thalamus were observed. The signal intensities of other regions measured were largely unchanged. During post-ingestive periods, the signals re-increased in the hypothalamic areas and AMc. When water was given, LHA and VMH were similarly activated, however, the signal intensity in the amygdala was not significantly increased. The results indicate that these brain regions are activated differentially during drinking behavior, and that LHA and VMH play a central role in the control of not only feeding but also drinking. The regional activities in LHA and VMH are not principally related to the gustatory sensation, and the reactivation after drinking may be related to satisfaction or post-ingestive nutritional information. Also, the responses of AMc are probably due to reward value difference. To the best of our knowledge, this is the first report of mapping of brain areas using fMRI in behaving rats. The improved method described in this study for collecting fMRI data in behaving animals will be useful for studying functional network during animal behavior.