Intake Of Sucrose Solution Research Articles

Sucrose Solution Ingestion Exacerbates Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats.

Allergic dermatitis is a skin disease with growing prevalence worldwide that has been associated with diets high in fats and sugars. Regular consumption of sucrose-containing beverages may increase the risk for several health problems, including allergic diseases and particularly asthma, but the association between sucrose consumption and allergic dermatitis is understudied. We investigated the effects of sucrose solution intake on allergic contact dermatitis in rats and found early exacerbation of 2,4-dinitrofluorobenzene (DNFB)-induced disease symptoms and altered composition of the gut microbiota after 14 d of intake. The levels of short-chain fatty acids-produced by fermentation by the intestinal microbiota-were not affected in the cecal contents and feces but decreased in the blood; this effect was especially notable for acetate. To restore blood acetate concentrations, triacetin was mixed with a 10% sucrose solution and fed to the rat model. This strategy prevented the early exacerbation of DNFB-induced symptoms. The decreased absorption of short-chain fatty acids from the intestinal lumen was not linked to the decreased expression of short-chain fatty acid transporters in the small intestine; instead, the mechanism involves a reduction in the sodium concentration in the intestinal lumen due to increased expression of sodium-glucose transporter 1 (SGLT1).

Traditional Japanese medicine Kamikihito ameliorates sucrose preference, chronic inflammation and obesity induced by a high fat diet in middle-aged mice.

The high prevalence of obesity has become a pressing global public health problem and there exists a strong association between increased BMI and mortality at a BMI of 25 kg/m2 or higher. The prevalence of obesity is higher among middle-aged adults than among younger groups and the combination of aging and obesity exacerbate systemic inflammation. Increased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha (TNFα) are hallmarks of obesity, and promote the secretion of hepatic C-reactive protein (CRP) which further induces systematic inflammation. The neuropeptide oxytocin has been shown to have anti-obesity and anti-inflammation effects, and also suppress sweet-tasting carbohydrate consumption in mammals. Previously, we have shown that the Japanese herbal medicine Kamikihito (KKT), which is used to treat neuropsychological stress disorders in Japan, functions as an oxytocin receptors agonist. In the present study, we further investigated the effect of KKT on body weight (BW), food intake, inflammation, and sweet preferences in middle-aged obese mice. KKT oral administration for 12 days decreased the expression of pro-inflammatory cytokines in the liver, and the plasma CRP and TNFα levels in obese mice. The effect of KKT administration was found to be different between male and female mice. In the absence of sucrose, KKT administration decreased food intake only in male mice. However, while having access to a 30% sucrose solution, both BW and food intake was decreased by KKT administration in male and female mice; but sucrose intake was decreased in female mice alone. In addition, KKT administration decreased sucrose intake in oxytocin deficient lean mice, but not in the WT lean mice. The present study demonstrates that KKT ameliorates chronic inflammation, which is strongly associated with aging and obesity, and decreases food intake in male mice as well as sucrose intake in female mice; in an oxytocin receptor dependent manner.

Reducing sugar intake through chronic swimming training: Exploring palatability changes and central vasopressin mechanisms

Excessive sugar intake has been associated with the onset of several non-communicable chronic diseases seen in humans. Physical activity could affect sweet taste perception which may affect sugar intake. Therefore, it was investigated the chronic effects of swimming training on sucrose intake/preference, reactivity to sucrose taste, self-care in neurobehavioral stress, and the possible involvement of the vasopressin type V1 receptor in sucrose solution intake. Male Wistar rats, of from different cohorts were used, subjected to a sedentary lifestyle (SED) or swimming training (TR - 1 h/day, 5×/week, for 8 weeks, with no added load). Weekly intake was verified in SED and TR rats after access to a sucrose solution 1×/week, 2 h/day, for eight weeks. Chronic effects of swimming and/or a sedentary lifestyle were carried out three days after the end of the physical exercise protocol. Swimming training reduced the intake of sucrose solution from the third week onwards in the two-bottle test measured once a week for 8 weeks. After the ending of the swimming protocol, sucrose intake was also reduced as per its preference. This reduced intake is probably correlated with the carbohydrate aspect of sucrose since saccharin intake was not affected. In addition, chronic swimming training was shown to reduce ingestive responses, increase neutral responses, without interfering with aversive, in the sucrose solution taste reactivity test. In addition, these results are not related to a depressive-like behavior, nor to neurobehavioral stress. Furthermore, treatment with vasopressin V1 receptor antagonist abolished the reduced sucrose intake in trained rats. The results suggest that swimming performed chronically is capable of reducing intake and preference for sucrose by decreasing the palatability of sucrose without causing depressive-type behavior or stress. In addition, the results also suggest that central V1 vasopressin receptors are part of the mechanisms activated to reduce sucrose intake in trained rats.

Effect of intranasal oxytocin on palatable food consumption and c-Fos immunoreactivity in relevant brain areas in rats

Peripheral and central injections of oxytocin (OT) in laboratory animals decrease eating for energy and palatability, but the hypophagic response is dependent on the administration route. Human studies rely on intranasal (IN) administration of the peptide, the route underutilized in OT animal feeding studies thus far. Therefore, we examined the effect of IN OT on various aspects of food consumption in rats: (a) overnight deprivation-induced standard chow intake, (b) episodic (2-h) consumption of calorie-dense and palatable high-fat high-sugar (HFHS) chow, (c) 2-h episodic intake of palatable and calorie-dilute sucrose and Intralipid solutions, and (d) 2-h sucrose solution intake in rats habituated to ingesting this solution daily for several weeks. Finally, we assessed c-Fos changes in response to the acute IN OT administration in rats habituated to daily sugar consumption. We found that IN 20μg OT decreased deprivation-induced intake of standard chow and HFHS chow in nondeprived rats without affecting water consumption. IN OT also reduced 2-hour episodic fluid consumption of sucrose, but not Intralipid. In the habitual sugar consumption paradigm, acute IN OT diminished sucrose solution intake in animals accustomed to the 2-hour/day sucrose meal regimen. In rats habitually consuming sucrose, IN OT altered c-Fos immunoreactivity in brain areas related to energy homeostasis and reward, including the central nucleus of the amygdala, the hypothalamic paraventricular and the arcuate nuclei. We conclude that IN OT is an effective appetite suppressant for carbohydrate/sugar diets in rats and its effects involve feeding-related brain circuits.

The Neonicotinoid Imidacloprid Impairs Learning, Locomotor Activity Levels, and Sucrose Solution Consumption in Bumblebees (Bombus terrestris).

Bumblebees carry out the complex task of foraging to provide for their colonies. They also conduct pollination, an ecosystem service of high importance to both wild plants and entomophilous crops. Insecticides can alter different aspects of bumblebee foraging behavior, including the motivation to leave the hive, finding the right flowers, handling flowers, and the ability to return to the colony. In the present study, we assessed how the neonicotinoid imidacloprid affects bumblebees' foraging behavior after exposure to four different treatment levels, including field-realistic concentrations (0 [control], 1, 10, and 100 μg/L), through sucrose solution over 9 days. We observed the behavior of several free-flying bumblebees simultaneously foraging on artificial flowers in a flight arena to register the bees' complex behavior postexposure. To conduct a detailed assessment of how insecticides affect bumblebee locomotor behavior, we used video cameras and analyzed the recordings using computer vision. We found that imidacloprid impaired learning and locomotor activity level when the bumblebees foraged on artificial flowers. We also found that imidacloprid exposure reduced sucrose solution intake and storage. By using automated analyses of video recordings of bumblebee behavior, we identified sublethal effects of imidacloprid exposure at field-realistic doses. Specifically, we observed negative impacts on consumption of sucrose solution as well as on learning and locomotor activity level. Our results highlight the need for more multimodal approaches when assessing the sublethal effects of insecticides and plant protection products in general. Environ Toxicol Chem 2023;42:1337-1345. © 2023 SETAC.

Intermittent sucrose solution intake and its schedule of access modulate energy intake and weight gain in response to chronic variable stress in mice

There is a strong relationship between stress and the intake of calorically-dense palatable food. Additionally, intake of sodas is an important contributory factor to obesity, and is often associated with palatable food consumption. We studied the effects of 2-h intermittent access to sucrose-sweetened water (SSW, 12.3%, soda-like) and its schedule of administration on the response to chronic variable stress in mice fed a high-fat, high-sugar diet. C57BL/6 mice (n = 64) had access to water or to both water and 2-h SSW during 5 weeks, in addition to their diet. After the first two weeks, half of the animals from each group were stressed daily using a chronic variable stress (CVS) paradigm, while the other half were kept undisturbed. During the CVS exposure period, 2-h SSW access was either scheduled randomly, right before the stressors or right after the stressors. The effects of SSW and its schedule of administration on dietary intake, stress hormones and adiposity were analyzed. Results showed a larger consumption of SSW and higher bodyweight gain in mice receiving SSW after the stressor. In addition, SSW consumption was shown to affect appetite regulation by reducing CCK sensitivity. The present study suggests that SSW leads to overconsumption and weight gain only if provided after exposure to stress. These findings may implicate a relation between exposure to stress, binge-drinking behaviors of sugar sweetened beverages that ensues, and weight gain in humans consuming a western diet.

Perturbation of amygdala/somatostatin-nucleus of the solitary tract projections reduces sensitivity to quinine in a brief-access test

Neural processing in the nucleus of the solitary tract (NST) is critical for concentration-dependent intake of normally preferred and avoided taste stimuli (e.g. affective responding); and is influenced by descending input from numerous forebrain regions. In one region, the central nucleus of the amygdala (CeA), a subpopulation of neurons that project to the NST express the neuropeptide somatostatin (Sst). The present study investigated whether this CeA/Sst-to-NST pathway contributes to concentration-dependent intake of sucrose and quinine hydrochloride (QHCl) solutions using brief-access lick trials (5 s). In both female and male mice, we used virus-based optogenetic tools and laser light illumination to manipulate the activity of CeA/Sst neurons that project to the NST. During light-induced inhibition of CeA/Sst-to-NST neurons, mice licked significantly more to our three highest concentrations of QHCl compared to control mice, while sucrose intake was unaffected. Interestingly, light-induced activation of this descending pathway did not influence licking of either sucrose or QHCl. These findings suggest that the CeA/Sst-to-NST pathway must be active for normal affective responding to an exemplary aversive taste stimulus.

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day.

Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin's effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored. This study examined the role of entrainment on intake patterns, oxytocin's effects on sucrose intakes and locomotor activity and whether oxytocin's effects were mediated by its actions at the oxytocin receptor. Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0mg/kg, 0.3mg/kg, 1mg/kg, 3mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access. Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear. Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we performed 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. Food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson’s disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particular the intake of fat.

Reduced caloric intake allows access-induced consumption differences to emerge with concentrated sucrose solutions

Rats given intermittent access to 4% (w/v) sucrose solution elevate their consumption of solution relative to rats with continuous access, a difference that does not appear at higher concentrations. Here, we examined the hypothesis that a limit on the intake of sucrose calories prevents rats from demonstrating access-induced differences in consumption of a more concentrated sucrose solution. Energy-replete rats were given every day (ED) or every third day (E3D) access to sucrose solutions adulterated with bitter quinine which reduced solution palatability and consumption levels while intake was measured. In experiment 1, previously collected data were compiled to examine the trajectory of consumption of continuously available 4% sucrose solution which was shown to stabilize by day 3 and then informed group assignment. In experiment 2, daily consumption levels were higher for rats with E3D access to 4% sucrose solution than rats with ED access to the same solution, whereas rats consumed similar amounts of 8% sucrose solution across access schedules. In the first hour of solution availability rats with E3D access showed elevated sucrose solution consumption, relative to rats with ED access, for both 4% and 8% sucrose solution. Upon the addition of quinine (0.005%) sucrose solution consumption decreased and the E3D access group consumed more daily sucrose solution than the ED access group for both 4% and 8% sucrose solution. In experiment 3, four groups of rats were given ED or E3D access to 8% sucrose solution adulterated with 0.0025%, 0.005%, 0.01%, or 0.02% quinine. Quinine adulteration reduced 8% sucrose solution consumption and allowed rats with E3D access to elevate their consumption levels relative to rats with ED access; this effect persisted when all groups were switched to 8% sucrose + 0.02% quinine solution. Thus, daily access-induced consumption differences develop but do not emerge because of a caloric limit on sucrose solution intake. This work underscores the interaction of availability and caloric intake as determinants of sugar consumption and highlights an important distinction between animal models of food addiction and binge eating.

The Differential Role of Cytokines on Stress Responses in a Menopause Rat Model.

Menopause is a risk factor of anxiety and depression. Also, psychoneurological symptoms are shown in almost all women in the perimenopausal period. The present study investigated if repeated stress modulates behavioral changes or the balance of pro- and anti-inflammatory cytokines in ovariectomized (OVX) rats. Albino SD female rats were randomly divided into four groups: the naïve normal group (NOR), a surgically ovariectomized group (OVX), the only stressed group (ST), and the OVX and stressed groups (OVX + ST). We performed a battery of tests such as the forced swimming test (FST), the sucrose intake, and social exploration. In the same animals, corticosterone (CORT) was assessed in the serum, and also, two representative cytokines (IL-1β and IL-4) were examined in different brain regions after all the behavior sessions for all the experimental groups. The OVX + ST group showed more immobility time in FST than the OVX group or the ST group. Also, the OVX + ST group tended to have a decreased active social exploration and sucrose solution intake compared to the OVX group or ST group. The serum concentration of CORT of the OVX + ST group was higher than the OVX group or ST group and also the level of CORT in OVX + ST was markedly increased compared to the NOR group. In the brain, the number of IL-1β immunoreactive neurons of the OVX + ST group was increased compared to the NOR group. The OVX + ST group tended to have an increase in IL-1β-positive neurons compared to the OVX or ST group. However, the number of IL-4 immunoreactive neurons of the OVX + ST group was markedly decreased compared with the NOR group. Also, the IL-4-positive neurons in the OVX + ST group was significantly decreased when compared to the ST group. These results indicate that ovariectomy and stress combine to increase the depressive-like behaviors and neuroinflammatory responses. Together, these data show neuroinflammation as a potential contributor to depressive-like symptoms during menopausal transition.

Exploring Anhedonia in Kennelled Dogs: Could Coping Styles Affect Hedonic Preferences for Sweet and Umami Flavours?

Simple SummaryKennelled dogs are susceptible to suffer chronic stress when social interactions with conspecifics and spatial needs are long-term restricted. Chronic stress may affect pleasure perception of food and solutions in dogs as observed in several animals, a phenomenon known as anhedonia. However, little information exists on how different coping styles could prevent the onset of anhedonia. Fourteen kennelled Beagle dogs were used to study the acceptability and preference for different dilute palatable sucrose and monosodium glutamate (MSG) solutions. Coping style of animals was previously evaluated through a modified human-approach test. This test consisted in assessing whether or not dogs approached an unfamiliar human when a feeding opportunity was presented, classifying them as close dogs (CD; proactive) or distant dogs (DD; reactive) respectively. It was observed that DD presented a lower intake of both sucrose and MSG dilute solutions compared with CD. Moreover, DD exhibited a higher consumption of MSG than CD at the highest concentrations, supporting that their intake depends on solution palatability. Finally, DD did not prefer sucrose or MSG solutions over water at any dilute solution offered. Together, these results suggest that dogs that are categorized as reactive animals could diminish their ability to perceive dilute palatable solutions reflecting depressive-like behaviours such as anhedonia.Kennelled dogs are at risk of suffering chronic stress due to long-term spatial, social and feeding restrictions. Chronic stress may decrease the dogs’ capacity to feel pleasure when facing hedonic experiences, modifying their perception for palatable ingredients. However, different abilities to cope with environmental stressors could prevent the onset of anhedonia. Fourteen kennelled Beagle dogs were used to study the acceptability and preference for different dilute sucrose and monosodium glutamate (MSG) solutions. Coping style of animals was previously evaluated through a human approach test (HAT) and classified as close dogs (CD; proactive) or distant dogs (DD; reactive) according to whether or not they approached an unfamiliar human when a feeding opportunity was presented. Consumption results were analysed taking into account the sucrose/MSG concentrations, HAT (CD or DD), age, and weight of the animals. DD presented a lower intake of sucrose (p = 0.041) and MSG (p = 0.069) solutions compared with CD. However, DD exhibited a higher consumption of MSG than CD at its highest concentrations, supporting that their intake depends on solution palatability. Finally, DD did not prefer sucrose or MSG solutions over water at any dilute solution offered. Together, these results suggest that dogs that are categorized as reactive animals could diminish their ability to perceive dilute palatable solutions, reflecting depressive-like behaviours as anhedonia.

Preference for vigorous exercise versus sedentary sucrose drinking: an animal model of anergia induced by dopamine receptor antagonism.

Motivation has activational and directional components. Mesolimbic dopamine is critical for the regulation of behavioral activation and effort-related processes in motivated behaviors. Impairing mesolimbic dopamine function leads to fatigue and anergia, but leaves intact other aspects of reinforce seeking behaviors, such as the consummatory or hedonic component. In male Swiss mice, we characterized the impact of dopamine antagonism on the selection of concurrently presented stimuli that have different vigor requirements. We analyzed running wheel activity versus sucrose solution intake, typically used as a measure of anhedonia. Results are compared with data from nonconcurrent presentation to those stimuli. In the concurrent presentation experiment, control mice preferred to spend time running compared to sucrose intake. Dopamine antagonism shifted relative reinforcer preference, reducing time spent on the running wheel, but actually increasing time-consuming sucrose. Mice increased frequency of bouts for both reinforcers, suggesting that there was fatigue in the running wheel rather than aversion. Moreover, satiation or habituation by preexposing animals to both reinforcers did not shift preferences. In the nonconcurrent experiments, haloperidol reduced running wheel but had no impact on sucrose consumption. Dopamine antagonism did not change preference for sucrose or total volume consumed. Additional correlational analyses indicated that baseline differences in sucrose consumption were independent of baseline running or novelty exploration. Thus, dopamine antagonism seems to have anergic rather than anhedonic effects, and the concurrent presentation in this setting could be useful for assessing preferences based on effort requirements.

Individual Differences in Behavioral Responses to Palatable Food or to Cholecystokinin Predict Subsequent Diet-Induced Obesity.

Objective:This study investigated whether individual differences in behavioral responses to palatable food and to the satiation signal cholecystokinin (CCK) in outbred chow-maintained Sprague Dawley rats enabled prediction of individual differences in weight gained after subsequent high-fat/high-sugar diet (HFHSD) maintenance.Methods:Meal size, meal number and early dark cycle intake during initial HFHSD exposure were measured as was early dark cycle sucrose solution and chow intake, chow meal size and meal number, the intake suppressive effect of 0.5μg/kg CCK injection, and CCK-induced c-Fos activation in the nucleus tractus solitarius (NTS). Subsequently, rats were maintained on HFHSD for five weeks and weight gain determined.Results:Rats that took larger and less frequent meals on the first day of HFHSD exposure, whose early dark cycle intake (HFHSD and sucrose) was larger during initial HFHSD exposure, gained more weight after HFHSD maintenance. Rats with lesser sucrose intake suppression in response to CCK gained more weight after HFHSD maintenance and also displayed reduced CCK-induced c-Fos activation in the NTS.Conclusions:Together, these data identify individual differences in behavioral responses to palatable food and to CCK as novel predictors of diet-induced obesity.

Amygdalar hyperactivation in response to safety signal in anxiety trait and generalised anxiety disorder

Although Parkinson's disease (PD) is characterized by progressive neurodegeneration of multiple neurotransmitter systems, 6-hydroxydopamine (6-OHDA) as a model substance is mainly used to selectively damage the nigrostriatal dopaminergic neurons and induce parkinsonian-like motor disturbances in rats. We hypothesized that high doses of this neurotoxin affecting other monoaminergic systems may also evoke the depressive-like behavior.The impact of 6-OHDA (8, 12, 16 μg/4 μl) administered unilaterally into the medial forebrain bundle on the sucrose solution intake (a measure of anhedonia) and on the tissue levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the striatum (STR), substantia nigra (SN), prefrontal cortex (PFC) and hippocampus (HIP) was examined in rats pretreated or non-pretreated with desipramine.The highest dose of 6-OHDA reduced the preference for 3% sucrose solution both in rats without and with desipramine pretreatment. All used doses of 6-OHDA dramatically decreased DA content in the studied brain structures on the ipsilateral side. NA levels were severely decreased in the ipsilateral STR, HIP and PFC of rats non-pretreated with desipramine and to a much lesser extent in those pretreated with desipramine. In the SN, moderate decreases in NA level were found both in rats pretreated and non-pretreated with desipramine. Higher doses of 6-OHDA reduced 5-HT content in the ipsilateral STR, HIP and PFC, but not in the SN, only in rats non-pretreated with desipramine.Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression.

Abdominal pumping involvement in the liquid feeding of honeybee

Honeybee drinking is facilitated by a “mop-like” tongue, which helps honeybees suck in the sucrose solution from the environment. However, the liquid-transport mechanism from the pharynx to the crop, especially the natural link between abdominal pumping and dipping behavior on the sucrose solution intake, remains obscure. A significant increase in abdominal pumping frequency is observed when honeybees drink the sucrose solution. Abdominal pumping exhibits a function other than respiration. This second function assists in driving the sucrose solution from the pharynx to the crop. We combine the experimental measurements using high-speed video and X-ray phase contrast imaging with theoretical modeling to investigate the effect of abdominal pumping in liquid feeding of honeybee. Experimental results show that a honeybee performs abdominal pumping in the abdomen at a faster rhythm during sucrose solution feeding than during other physiological activities. In addition, the period of abdominal pumping is in concordance with that of dipping cycles. Theoretical analysis demonstrates that the abdomen, which is comparable with a micro pump, changes its volume rhythmically. Such expansion reduces pressure in the abdomen, which also reduces pressure in the crop and helps propel the sucrose solution from the pharynx to the crop. Abdominal pumping can help honeybees improve their feeding efficiency and save foraging time. This research work reveals a specific feeding mechanism of insects fed on sucrose solution and opens a new way for the design of microfluidic pump.

Effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion in mice: the role of TGF-β1 in brain tissues

Objective To evaluate the effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion (I/R) in mice and the role of transforming growth factor-beta 1 (TGF-β1)in brain tissues. Methods Sixty healthy SPF male C57BL/6J mice, weighing 23-25 g, aged 8-10 weeks, were divided into 5 groups (n=12 each) using a random number table method: sham operation group (group Sham), I/R group, dexmedetomidine group (group D), dexmedetomidine plus IgG1 isotype control monoclonal antibody group (group DI) and dexmedetomidine plus TGF-β1 neutralizing monoclonal antibody group (group DA). Cerebral I/R was induced by occlusion of the middle cerebral artery followed by reperfusion.Dexmedetomidine 50 μg/kg was intraperitoneally injected every 24 h for 14 days starting from 14 days of reperfusion in group D. TGF-β1 neutralizing monoclonal antibody 20 μg and IgG1 isotype control monoclonal antibody 20 μg were intraperitoneally injected at 30 min prior to dexmedetomidine injection in group DA and group DI, respectively.5-bromodeoxyuridine (BrdU) 100 mg/kg was intraperitoneally injected and injected again at an 8-h interval on 27 days of reperfusion.Forced swimming test (FST), sucrose consumption test (SCT) and open field test (OFT) were performed at 16 h after the second administration of BrdU.After the end of behavior testing, the number of Ki67, BrdU and BrdU/DCX positive cells in the subventricular zone on ischemic side was measured by immunohistochemistry, and the expression of TGF-β1 protein and mRNA in brain tissues in ischemic area was detected using Western blot and real-time polymerase chain reaction, respectively. Results Compared with group Sham, the time spent floating in FST was significantly prolonged, the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased, the number of Ki67, BrdU and BrdU/DCX positive cells in the subventricular zone was increased, and the expression of TGF-β1 protein and mRNA was up-regulated in group I/R (P 0.05). Conclusion Dexmedetomidine can relieve depression and anxiety following cerebral I/R, thus promotes nerve regeneration and the mechanism is related to up-regulating the expression of TGF-β1 in brain tissues of mice. Key words: Dexmedetomidine; Reperfusion injury; Brain; Transforming growth factor beta1; Nerve regeneration

Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress

AimsOur previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. Main methodsThe rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Key findingsDesipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. SignificanceOur findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress.

Depressive-like neurochemical and behavioral markers of Parkinson's disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle.

Although Parkinson's disease (PD) is characterized by progressive neurodegeneration of multiple neurotransmitter systems, 6-hydroxydopamine (6-OHDA) as a model substance is mainly used to selectively damage the nigrostriatal dopaminergic neurons and induce parkinsonian-like motor disturbances in rats. We hypothesized that high doses of this neurotoxin affecting other monoaminergic systems may also evoke the depressive-like behavior. The impact of 6-OHDA (8, 12, 16μg/4μl) administered unilaterally into the medial forebrain bundle on the sucrose solution intake (a measure of anhedonia) and on the tissue levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the striatum (STR), substantia nigra (SN), prefrontal cortex (PFC) and hippocampus (HIP) was examined in rats pretreated or non-pretreated with desipramine. The highest dose of 6-OHDA reduced the preference for 3% sucrose solution both in rats without and with desipramine pretreatment. All used doses of 6-OHDA dramatically decreased DA content in the studied brain structures on the ipsilateral side. NA levels were severely decreased in the ipsilateral STR, HIP and PFC of rats non-pretreated with desipramine and to a much lesser extent in those pretreated with desipramine. In the SN, moderate decreases in NA level were found both in rats pretreated and non-pretreated with desipramine. Higher doses of 6-OHDA reduced 5-HT content in the ipsilateral STR, HIP and PFC, but not in the SN, only in rats non-pretreated with desipramine. Administration of the highest dose of 6-OHDA without desipramine pretreatment evoked neurochemical and behavioral changes resembling the advanced PD with coexisting depression.

A method for the assessment of facial hedonic reactions in newborns

ObjectiveThis study describes a quantitative and qualitative methodology to assess hedonic responses to sweet stimulus in healthy newborns. MethodsA descriptive, cross‐sectional, observational study, with healthy newborns (up to 24h of life), between 37 and 42 gestational weeks, vaginally born and breastfed previously to all tests. The evaluation of the newborns reactions was performed by hedonic facial expression analysis, characterized by facial expressions with rhythmic serial tongue protrusion after neutral or sweet solution intake. Initially, 1mL of water solution was provided to the newborn, followed by a 1‐minute recording. Afterwards, the same amount of 25% sucrose solution was provided, performing a second recording. The concordance between researchers was analyzed by the Bland–Altman statistical method. ResultsA total of 100 newborns (n=49 males, n=51 females; mean lifetime=15h 12min±6h 29min) were recorded for neutral and sucrose solution intake, totaling 197 videos (n=3 missing in the water treatment). These videos were double‐blind analyzed and the test revealed a 90% concordance between the two trained researchers, in relation to both solutions. The intraclass correlation coefficient was 0.99 for both solutions, with a significant increase in frequency of hedonic expressions evoked by sucrose solution intake. ConclusionsThese results confirm that the proposed method has an efficient power to detect significant differences between neutral and sucrose stimuli. In conclusion, this evaluation method of hedonic facial reactions in newborns reflects the response to a specific taste.