Sang Bae Yoo

Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats.

This study was conducted to define the regulatory mechanisms underlying stress-induced decreases in food intake and weight gain. Rats received a single or 4 daily injections of dexamethasone (0.1 or 1 mg/kg). Food intake and weight gain were recorded, and plasma leptin, brain contents of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxy-indole-acetic acid (5-HIAA) and the raphe expression of tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and 5-HT reuptake transporter (5-HTT) genes were examined. A single injection of dexamethasone did not acutely affect food intake, but cumulative food intake and weight gain were suppressed dose-dependently by daily injections of dexamethasone. Both a single and repeated injections of dexamethasone elevated plasma leptin in a dose dependent manner. 5-HT contents in the hypothalamus was decreased, but 5-HIAA increased, both by a single and repeated dexamethasone. A single injection of dexamethasone did not affect mRNA expressions of TPH, MAO-A and 5-HTT genes, but repeated dexamethasone increased them in the dorsal raphe nucleus. These results suggest that plasma leptin may play a role in dexamethasone-induced anorexia. Additionally, increased expression of MAO-A and 5-HTT genes by repeated dexamethasone appears to be implicated in decreases of the brain 5-HT contents.

Post-weaning isolation promotes food intake and body weight gain in rats that experienced neonatal maternal separation.

Neonatal maternal separation (MS) in rats has been reported to result in permanent dysfunctions of the hypothalamic-pituitary-adrenal axis and the development of anxiety- and depression-like behaviors later in life. In this study, we examined the effects of post-weaning social isolation stress on food intake and body weight gain of rats with MS experience. MS was performed daily for 180 min during the first 2 weeks of birth and nonhandled control (NH) pups were left undisturbed. Weanling male pups were caged either in a group of three or singly (social isolation), and then subjected to behavioral sessions for anxiety- or depression-like behaviors at 2 months of age. Social isolation following MS experience, but neither MS nor social isolation alone, significantly increased food intake and weight gain. MS pups showed increased immobility in forced swim test, compared to NH pups, regardless of their housing conditions. In elevated plus maze test, group-caged MS pups spent less time in the open arms and more time in the closed arms than group-caged NH pups, but social isolation did not further affect the arm stay of MS pups. However, statistical analyses revealed an interaction between MS and social isolation not only in the time spent in each arms, but also in defecation scores during the ambulatory activity test. These results suggest that post-weaning social isolation may promote hyperphagia and weight gain in young rats that experienced neonatal maternal separation, perhaps, in relation with its impact on the psycho-emotional behaviors of MS pups.

Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus axis and improves depression-like behaviors in female rats that experienced neonatal maternal separation.

This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females.

Hyperphagia and depression-like behavior by adolescence social isolation in female rats.

This study was conducted to examine the effects of adolescence social isolation on food intake and psycho‐emotional behaviors of female rats. Female littermates were either single‐caged (social isolation) or group‐caged (control) from postnatal day 28, and then subjected to behavioral sessions during postnatal day 50–53. Body weight gain of the isolates was accelerated during the experimental period and food intake was persistently greater than group‐caged controls from postnatal day 35. Isolated females showed a selective increase in cookie intake when they had additional cookie access to standard chow. The isolates exhibited hyperactivity with increased ambulatory counts and rearings during the activity test as compared with group‐caged controls. Behavioral scores of the elevated plus maze test did not differ between the isolates and group‐caged controls; however, immobility time during the forced swim test was significantly increased in the isolates. Basal levels of plasma corticosterone were elevated, but the corticosterone increase responding to an acute stress was blunted, in the isolates compared with group‐caged ones. Results suggest that adolescence social isolation induces hyperphagia and depression‐like behaviors in female rats and a tonic increase of plasma corticosterone may be implicated in its underlying mechanisms.

Capsaicin receptors are colocalized with sweet/bitter receptors in the taste sensing cells of circumvallate papillae.

We examined co-localization of vanilloid receptor (VR1) with sweet receptors T1R2, T1R3, or bitter receptor T2R6 in taste receptor cells of rat circumvallate papillae. Tissue sections of rat circumvallate papillae were doubly reacted with anti-VR1 antibodies and anti-T1R2, anti-T1R3 or anti-T2R6 antibodies, using double-immunofluorescence histochemistry technique. Localizations of VR1, T1Rs and T2R6 in the vallate taste cells containing α-gustducin were also examined. VR1 immunoreactivities (-ir) were observed in subsets of taste cells in the circumvallate papillae, and 96–99% of the vallate taste cells exhibiting T1R2-, T1R3- or T2R6-ir co-exhibited VR1-ir. Approximately half of T2R6-ir cells (~49%), and 50–58% of T1Rs-ir cells, co-exhibited α-gustducin-ir in the vallate taste buds. About 58% of VR1-ir cells in the vallate exhibited α-gustducin-ir as well. Results support the idea that capsaicin may interact with the transduction pathways of sweet and bitter taste stimuli, possibly in mediation of its receptor VR1 localized in taste receptor cells. Additionally, the partial co-localization of α-gustducin with VR1 suggests that a tentative modulatory function of capsaicin in sweet and bitter transductions in the rat circumvallate comprises of both α-gustducin-mediated and non-mediated transduction pathways.

Recombinant human nerve growth factor (rhNGF-β) gene transfer promotes regeneration of crush-injured mental nerve in rats

OBJECTIVE The aim of this study was to evaluate whether the recombinant human nerve growth factor (rhNGF-β) gene transfer at a crush-injured sensory nerve can enhance nerve regeneration. STUDY DESIGN A 4-mm crush injury was made on the mental nerve of mandible in rats, and rhNGF-β adenovirus (6 μL, concentration = 1.0 × 10(11) pfu/μL) was injected at the crushed site for the experimental group (NGF-Ad group, n = 15) and the same volume of PBS for the controls (PBS group, n = 15). A sham group of uninjured nerve was also used for the normal control (Sham group, n = 15). The effect of rhNGF-β adenovirus injection was evaluated by real-time reverse trascriptase polymerase chain reaction for the quantification of nerve growth factor (NGF), low-affinity NGF receptor (p75NTR), and its tyrosine receptor kinase A (trkA) mRNA expression at the trigeminal ganglion (TG) 5 days after injection. Nerve regeneration was evaluated with sensory test, retrograde axonal transport in the TG, and histomorphometric study for 4 weeks. RESULTS NGF, p75NTR, and trkA mRNA expression was significantly increased at the TG 5 days after injection of rhNGF-β adenovirus (P < .05). The NGF-Ad group showed improved sensory recovery (P < .05), and the number of retrograde-labeled sensory neurons and soma size of TG were larger compared with the PBS groups (P < .05). Histomorphometrically, the myelinated axon number, myelin thickness, and G-ratio in the NGF-Ad group was also significantly higher than the PBS groups (P < .05). CONCLUSIONS Recombinant human nerve growth factor gene transfer promoted regeneration of crush-injured mental nerve.

Intra-oral pre-treatment with capsaicin increases consumption of sweet solutions in rats.

Abstract Sprague-Dawley rats received preference tests for sucrose or saccharin daily following oral treatment with 0.02% capsaicin. Consumed sweet solutions and preference scores increased in capsaicin-treated rats, compared to control rats on the second to fifth exposure period for sucrose and all exposure periods for saccharin. Chow intake was not affected by repeated treatment with capsaicin. Real-time RT-PCR analysis revealed decreased expression of sweet receptors T1R2 and T1R3 as well as capsaicin receptor VR1 in the circumvallate after this repeated oral exposure to capsaicin. VR1 immunoreactivities were also localized in the vallate taste cells by fluorescence immunohistochemistry. Results suggest that decreased expression of sweet receptors in the circumvallate may be related to increased sweet consumption in capsaicin-treated rats; any causal relationship should be further studied. Also, these data suggest that capsaicin may interact with a sweet transduction pathway in the mediation of its receptor VR1 that are located in the vallate taste cells.

Increased Mesohippocampal Dopaminergic Activity and Improved Depression-Like Behaviors in Maternally Separated Rats Following Repeated Fasting/Refeeding Cycles

We have previously reported that rats that experienced 3 h of daily maternal separation during the first 2 weeks of birth (MS) showed binge-like eating behaviors with increased activity of the hypothalamic-pituitary-adrenal axis when they were subjected to fasting/refeeding cycles repeatedly. In this study, we have examined the psychoemotional behaviors of MS rats on the fasting/refeeding cycles, together with their brain dopamine levels. Fasting/refeeding cycles normalized the ambulatory activity of MS rats, which was decreased by MS experience. Depression-like behaviors, but not anxiety, by MS experience were improved after fasting/refeeding cycles. Fasting/refeeding cycles did not significantly affect the behavioral scores of nonhandled (NH) control rats. Fasting/refeeding cycles increased dopamine levels not only in the hippocampus but also in the midbrain dopaminergic neurons in MS rats, but not in NH controls. Results demonstrate that fasting/refeeding cycles increase the mesohippocampal dopaminergic activity and improve depression-like behaviors in rats that experienced MS. Together with our previous paper, it is suggested that increased dopamine neurotransmission in the hippocampus may be implicated in the underlying mechanisms by which the fasting/refeeding cycles induce binge-like eating and improve depression-like behaviors in MS rats.

Ingestion of non-caloric liquid diet is sufficient to restore plasma corticosterone level, but not to induce the hypothalamic c-Fos expression in food-deprived rats

Abstract Male Sprague-Dawley rats were subjected to four different conditions; free fed control (FC), 48 h of food deprivation (FD), 1 h of refeeding with chow (RF/CW) or with a non-caloric liquid diet following FD (RF/NC) and then sacrificed for c-Fos immunohistochemistry in the hypothalamic paraventricular nucleus (PVN) and the nucleus tractus of solitarius (NTS). Plasma corticosterone level and the postmortem weight of gastric contents were measured. Plasma level of corticosterone significantly increased during FD, and then decreased within 1 h after ad libitum access to chow or non-caloric liquid diet. c-Fos-ir in the brain regions was not changed by FD; however, significantly increased by chow refeeding, but not by non-caloric diet. Chow, but not the non-caloric, refeeding significantly increased gastric contents. Results suggest that caloric load and/or gastric distension may require for the postprandial activation of neurons in the PVN and NTS, but ingestion of non-caloric palatable mixture may be sufficient to normalize the fasting-induced increase of plasma corticosterone. In conclusion, feeding-related changes in the HPA axis activity may not be related with meal-induced c-Fos expression in the PVN and NTS.

Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves

Several studies have demonstrated that human umbilical cord blood-derived mesenchymal stem cells can promote neural regeneration following brain injury. However, the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells in guiding peripheral nerve regeneration remain poorly understood. This study was designed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells on neural regeneration using a rat sciatic nerve crush injury model. Human umbilical cord blood-derived mesenchymal stem cells (1 × 106) or a PBS control were injected into the crush-injured segment of the sciatic nerve. Four weeks after cell injection, brain-derived neurotrophic factor and tyrosine kinase receptor B mRNA expression at the lesion site was increased in comparison to control. Furthermore, sciatic function index, Fluoro Gold-labeled neuron counts and axon density were also significantly increased when compared with control. Our results indicate that human umbilical cord blood-derived mesenchymal stem cells promote the functional recovery of crush-injured sciatic nerves.