Developmental changes in the hypothalamic mRNA expression levels of brain-derived neurotrophic factor and serum leptin levels: Their responses to fasting in male and female rats

The actions and responses of hypothalamic appetite regulatory factors change markedly during the neonatal to pre-pubertal period in order to maintain appropriate metabolic and nutritional conditions. In this study, we examined the developmental changes in the hypothalamic mRNA levels of brain-derived neurotrophic factor (BDNF), which is a potent anorectic factor and the changes in the sensitivity of the hypothalamic expression of this factor to fasting during the neonatal to pre-pubertal period. Under fed conditions, hypothalamic BDNF mRNA expression decreased during development in both male and female rats. Similarly, the serum levels of leptin, which is a positive regulator of hypothalamic BDNF expression, also tended to fall during the developmental period. The serum leptin level and the hypothalamic BDNF mRNA level were found to be positively correlated in both sexes under the fed conditions. Hypothalamic BDNF mRNA expression was decreased by 24 h fasting (separating the rats from their mothers) in the early neonatal period (postnatal day 10) in both males and females, but no such changes were seen at postnatal day 20. Twenty-four hours’ fasting (food deprivation) did not affect hypothalamic BDNF mRNA expression in the pre-pubertal period (postnatal day 30). On the other hand, the rats’ serum leptin levels were decreased by 24 h fasting (separating the rats from their mothers at postnatal day 10 and 20, and food deprivation at postnatal day 30) throughout the early neonatal to pre-pubertal period. The correlation between serum leptin and hypothalamic BDNF mRNA levels was not significant under the fasted conditions. It can be speculated that leptin partially regulates hypothalamic BDNF mRNA levels, but only in fed conditions. Such changes in hypothalamic BDNF expression might play a role in maintaining appropriate metabolic and nutritional conditions and promoting normal physical development. In addition, because maternal separation induces a negative energy balance and short- and long-term stress responses, it is also possible that reductions in hypothalamic BDNF mRNA levels in the early neonatal period (postnatal day 10) may be partially induced by stress responses of the maternal deprivation.     

Changes in the responsiveness of serum leptin and hypothalamic neuropeptide Y mRNA levels to food deprivation in developing rats

Neuropeptide Y (NPY) is an important orexigenic peptide that acts in the brain. The increase in hypothalamic NPY mRNA expression induced by fasting is mainly caused by a decrease in the effects of leptin. We investigated the developmental changes in the sensitivities of leptin and hypothalamic neuropeptide Y to fasting. Hypothalamic NPY mRNA levels were increased by fasting in postnatal days 15 and 25 rats, but not in postnatal day 5 rats. Serum leptin levels were decreased by fasting in rats at all ages (days 5, 15, and 25). In addition, hypothalamic OB-Rb mRNA levels were decreased by fasting in postnatal day 25 rats, but not in postnatal day 5 or 15 rats. Although the percentage of fating-induced decrease in the serum leptin level was larger in the postnatal day 15 rats than in the postnatal day 25 rats, the percentage of increase in the hypothalamic NPY mRNA level in the postnatal day 15 rats was smaller than that in the postnatal day 25 rats. There was a strong inverse correlation between serum leptin levels and hypothalamic NPY mRNA levels in the postnatal day 25 rats, whereas no significant correlation was found between these parameters in the postnatal day 5 or 15 rats. These findings indicate that the sensitivity of hypothalamic NPY mRNA expression to food deprivation and hypoleptinemia has developed by postnatal day 25.     

The effect of carbamazepine treatment on serum leptin levels

Patients with epilepsy may manifest metabolic adverse effects throughout the course of their management with antiepileptic drugs. Leptin is a hormone that plays a major role in the regulation of feeding and energy expenditure. Leptin has been expected to form a link to weight gain in epilepsy with the use of some antiepileptic drugs. The aim of this study is to evaluate the effect of carbamazepine on body weight and serum leptin levels.This study was conducted in Izmir Tepecik Training and Research Hospital, Neurology Department. 56 epileptic patients who were on continuous carbamazepine monotherapy for at least 6 months before the study and 42 control subjects were included. Serum leptin and insulin levels were measured.Body mass index, leptin and insulin were not significantly elevated in carbamazepine group compared to control subjects (p > 0.05).Our study demonstrated that carbamazepine therapy does not affect significantly body mass index, leptin and insulin. Data regarding the effect of carbamazepine on serum leptin level is limited but the results of these recent studies are correlated with ours. It can be concluded that carbamazepine is a relatively low risky antiepileptic drug in terms of obesity and metabolic syndrome but further studies are needed.     

首发精神分裂症患者利培酮治疗前后血浆瘦素和白细胞介素-6的研究

目的探讨精神分裂症患者利培酮治疗前后血浆瘦素和白细胞介素-6(IL6)水平的变化及意义。方法患者组为65例首发的精神分裂症患者,利培酮治疗前和治疗8周后分别测量身高、体重以计算体质量指数,用放射免疫方法检测其空腹血浆瘦素和IL6。选取52名健康人作为对照组进行比较。结果治疗后患者组体质量指数、血浆瘦素水平均明显上升,与治疗前比较差异有显著性(P均小于0.05);患者组血浆IL6水平在治疗前与对照组相比明显增高,治疗后明显下降,与治疗前比较差异有显著性(P均小于0.05);治疗前后血浆瘦素的差值和IL6的差值呈负相关(r=-0.388,P<0.05)。结论首发精神分裂症患者血浆IL6水平高于对照组,服用利培酮治疗容易出现药源性肥胖,增高的IL6水平可能是瘦素抵抗的原因之一;过高的瘦素水平与IL6之间可能存在负反馈。     

The effects of prenatal undernutrition and postnatal high-fat diet on hypothalamic Kiss1 mRNA and serum leptin levels

Prenatal undernutrition and postnatal overnutrition increase the risk of some metabolic disorders in adulthood, and hypothalamic leptin resistance makes an important contribution to these effects. Leptin plays important roles in the maintenance of reproductive function, and its actions might be partially mediated by kisspeptin, which is a potent positive regulator of gonadotropin-releasing hormone. In this study, the effects of prenatal undernutrition and postnatal overnutrition on reproductive parameters and sexual maturation during the peripubertal period were evaluated. Rats subjected to prenatal undernutrition (IUGR) and fed a postnatal high-fat diet (HFD) (n = 7) exhibited 40% higher serum leptin levels and 30% lower hypothalamic Kiss1 (the gene encoding kisspeptin) mRNA levels than those subjected to prenatal undernutrition (IUGR) and fed a normal diet (n = 7). No such HFD-induced postnatal alterations were observed in the rats fed a normal diet during the prenatal period (control) (n = 7 per group). Although the consumption of the HFD did not affect the serum luteinizing hormone levels or body weight of the IUGR or control rats, it did promote vaginal opening in both groups (evaluated in 14 rats per group). These findings indicate that hypothalamic leptin resistance might occur in IUGR-HFD rats, but these changes do not influence downstream effectors of the reproductive endocrinological system. They also suggest that the relationships between nutritional conditions, body weight, reproductive factors, and sexual maturation are complex.     

缬沙坦胶囊对阿尔茨海默病患者血清脂联素、瘦素水平的影响

目的 探讨脂联素(APN)、瘦素(LEP)在阿尔茨海默病(AD)患者血清中的变化及缬沙坦胶囊治疗AD的可能机制.方法 选取AD患者为研究对象,分为缬沙坦组及对照组,通过认知能力筛查(CASI)-2量表评估AD患者认知损害程度,通过酶联免疫吸附法检测血清APN、LEP的变化.结果 治疗前,缬沙坦组CASI量表评分、血清APN、LEP水平与对照组比,差异无统计学意义(P＞0.05);治疗后,缬沙坦组患者CASI量表评分较对照组改善(P＜0.05);血清APN、LEP水平较对照组增高(P＜0.05).结论 缬沙坦胶囊可以在一定程度上延缓AD的进展,其作用可能通过升高血清APN及LEP的水平来实现.     

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.     

拉莫三嗪对成年癫患者血清中瘦素、抵抗素和脂联素水平的影响

目的探讨抗癫新药拉莫三嗪对成年癫患者血清瘦素、抵抗素、脂联素水平的影响。方法对30名女性健康查体人员和60例首发癫全面性强直-阵挛发作女性患者随机分为拉莫三嗪组和丙戊酸钠组,在治疗前和治疗后分别进行血清瘦素、抵抗素和脂联素水平测定,并测量腰臀比(帆)、体重指数(BMI)。结果拉莫三嗪治疗后、对照组BMI、WHR及血清瘦素、抵抗素、脂联素水平间均无明显差异,而丙戊酸钠治疗后血清瘦素、抵抗素水平明显升高,脂联素水平明显降低(P<0.01)。结论拉莫三嗪治疗不引起癫患者体重增加,瘦素、脂联素、抵抗素水平可能是肥胖发生的预测指标。     

Effects of sex and androgen treatment on dendritic dimensions of neurons in the sexually dimorphic preoptic/anterior hypothalamic area of male and female ferrets.

A sexually dimorphic group of cells at the dorsal border of the preoptic/anterior hypothalamic area (POA/AH) of ferrets has been previously identified in Nissl-stained tissue. In this study, Golgi-stained tissue was examined in order 1) to determine whether sex differences exist in dendritic dimensions of neurons from this region, and 2) to assess the effects of adult androgen treatment on dendritic morphology in ferrets of both sexes. Brains from adult ferrets given daily injections of testosterone propionate (5 mg/kg body weight) or oil vehicle for 5 weeks after gonadectomy were impregnated by Golgi-Cox procedures. After sectioning at 120 microns, 78 multipolar neurons were selected from the sexually dimorphic POA/AH of 12 ferrets and reconstructed in three dimensions with the aid of a computer-assisted neuron tracing system. Large sex differences were observed in somal area and most aspects of dendritic morphology, including total length, number of branches, and total dendritic surface area. Androgen also appeared to accentuate dendritic arborization in both sexes, but this effect was weaker than the sex effect, more apparent in males than females, and restricted to fewer variables. The most statistically significant effects of adult androgen treatment in males were found for total dendritic surface area and percentage of fourth order dendrites, and in females, average dendritic thickness. These data show that strong sex differences exist in dendritic structure of neurons in the POA/AH, and suggest that alterations in levels of gonadal steroids in adulthood may promote synaptic remodeling in a region of the brain involved in the control of sexually dimorphic behaviors.     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

Impact of CPAP treatment on leptin and adiponectin in adults with coronary artery disease and nonsleepy obstructive sleep apnoea in the RICCADSA trial

BackgroundIncreased leptin and decreased adiponectin levels are reported in coronary artery disease (CAD) as well as in obstructive sleep apnoea (OSA). Less is known regarding the impact of continuous positive airway pressure (CPAP) on these biomarkers. We aimed to determine variables associated with leptin and adiponectin in adults with CAD and nonsleepy OSA, and evaluate the effect of CPAP adjusted for confounding factors.MethodsThis was one of the secondary outcomes of the RICCADSA trial, conducted in Sweden between 2005 and 2013. From 244 revascularized CAD and OSA patients (apnoea–hypopnoea index >15/h) without excessive daytime sleepiness (Epworth Sleepiness Scale score <10), 196 with blood samples at baseline, after 3, and 12 months were included in the randomized controlled trial arm; of those, 98 were allocated to auto-titrating CPAP, and 98 to no-CPAP.ResultsNo significant changes in leptin and adiponectin levels were observed during follow-up, whereas Body-Mass-Index and waist circumference increased in both CPAP and no-CPAP groups with no significant between-group differences. Alterations in plasma leptin were determined by changes in waist circumference (beta coefficient 2.47; 95% confidence interval 0.77–4.40), whereas none of the analyzed parameters was predictive for changes in adiponectin levels. No association was found with CPAP adherence.ConclusionsCPAP had no significant effect on leptin and adiponectin in this cohort of nonsleepy OSA patients. An increase in waist circumference predicted an increase in plasma levels of leptin after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA regardless of CPAP treatment.     

Effects of lesions of a sexually dimorphic nucleus in the preoptic/anterior hypothalamic area on the expression of androgen- and estrogen-dependent sexual behaviors in male ferrets

The male nucleus of the preoptic/anterior hypothalamic area (MN-POA/AH) is a sexually dimorphic structure present in male, but not in female ferrets. Ovariectomized female ferrets given increasing dosages of estradiol benzoate (EB) normally run faster towards a stud male in an L-maze (i.e. become more proceptive). In two separate experiments, only gonadectomized males with bilateral damage to the MN-POA/AH following large or small electrolytic lesions approached stud males more quickly in response to EB. By contrast, males which received sham lesions, unilateral large POA/AH lesions, or bilateral lesions which missed the MN-POA/AH on at least one side failed to show EB-induced reductions in approach latencies in pre- or post-operative tests. Males with large POA/AH lesions also displayed significant post-operative decrements in masculine sexual behaviors during treatment with a high dose of testosterone propionate (TP). Less severe, but statistically significant deficits in masculine coital performance were also observed in males with small lesions which damaged the MN-POA/AH bilaterally; however, the ability of these males to achieve intromissions appeared normal. Together, these results suggest that the MN-POA/AH of the male ferret exerts an inhibitory influence on estrogen-dependent proceptive responsiveness, but play only a minor role in the control of masculine coital behavior.     

The effects of topiramate and valproate therapy on insulin,c-peptide,leptin, neuropeptide Y,adiponectin, visfatin,and resistin levels in children with epilepsy

PurposeAntiepileptic drugs may affect the endocrine system. We investigated the effects of valproic acid and topiramate on the levels of insulin, c-peptide and adipocytokines in pre-pubertal patients with idiopathic partial and generalized epilepsy.MethodsForty-one children with epilepsy were included. The patients were divided into two groups (valproic acid; n = 21, topiramate; n = 20). The weight, height, body mass index and homeostasis model assessment of insulin resistance (HOMA-IR) were recorded and insulin, c-peptide, leptin, neuropeptide Y, adiponectin, visfatin and resistin levels were determined at 0, 6 and 12 months of therapy.ResultsIn the valproate group, weight and height increased significantly. Seven of 21 patients were overweight at the end of one year. Leptin was higher in the overweight subgroup. Although insulin and HOMA-IR increased (p < 0.05), none of the patients showed hyperinsulinism or IR. Resistin had decreased at the 6th and 12th months (p < 0.05). In the topiramate group, some statistically nonsignificant changes were demonstrated.ConclusionThe mechanisms behind valproate and topiramate-related weight control are still unclear, especially in children. Valproate and topiramate affect the weight, BMI, and insulin, leptin and adipocytokine levels in prepubertal children. We suggest that further studies including more patients with a long follow-up period are necessary to draw a firm conclusion regarding an association between the treatment with these drugs and the levels of leptin, insulin and adipocytokines.     

Lack of effect of chronic morphine treatment and naloxone-precipitated withdrawal on tyrosine hydroxylase,galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus

Morphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days. Withdrawal was precipitated in half of the morphine-dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal weret evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropep tide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone-precipitated withdrawal. In contrast, mRNA levels for c fos were dramatically elevated in the LC following naloxone-precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing factor (CRF) in Barrington's nucleus. Although long-term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process. © 1995 Wiley-Liss, Inc.     

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 ± 2.0 ng/ml vs.11.9 ± 2.3 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 ± 2.3 ng/ml) compared to those with clozapine (10.2 ± 2.0 ng/ml, p < 0.001) and typical antipsychotics (10.0 ± 2.1 ng/ml, p < 0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta = − 0.37, t = − 3.15, p = 0.001) and BDNF levels (beta = − 0.26, t = − 2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7 ± 1.9 ng/ml for males vs.10.4 ± 2.1 ng/ml for female, p < 0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.     

Retrospective analysis of the correlation between serum vitamin D levels and blood amino acids levels in children with autism: Exploration of possible mechanisms of the effect of vitamin D on autism

Hypovitaminosis D has been recognized as a risk factor for autism spectrum disorder (ASD); however, its mechanism remains unclear. Amino acid metabolism is involved in the related factors of ASD, such as neurotransmitters, oxidative stress, and immune dysfunction. Vitamin D not only regulates the activity of the amino acid transport system, but is also closely related to amino acids in the regulation of immunity and oxidative stress. To investigate the possible mechanisms by which vitamin D may influence ASD, the correlation between blood amino acids and serum 25(OH)D levels of 506 children (411 males and 95 females) with ASD were retrospectively analyzed, and possible related pathways were determined via a literature review. According to the results, alanine, arginine, glycine, ornithine, glutamine and histidine were found to be significantly negatively correlated with serum 25(OH)D levels (P < 0.05). Glycine and ornithine were also found to be influenced by age, and glutamine levels were different in male and female children with ASD. In addition, there were differences in alanine levels in different BMI levels. However, after adjusting for the influences of these factors in the regression equation, it was found that 25(OH)D was associated with the identified 6 amino acids (P < 0.05). Therefore, vitamin D may influence ASD through the cross-pathways of these amino acids (i.e. glutamine-gamma aminobutyric acid balance, oxidative stress, and immune dysfunction). This conclusion may provide some ideas for further investigation of the effect of vitamin D on ASD.     

Roux-y乙状结肠新膀胱替代后肠黏膜组织学变化及对代谢的影响

背景：许多报道指出,尿流改道后会出现代谢紊乱和病理生理的变化,但是这些用肠道重建膀胱替代手术引起的代谢紊乱主要与肠管类型及长度相关。 目的： 观察Roux-y乙状结肠新膀胱替代后贮尿囊黏膜的变化及对代谢的影响。 设计、时间及地点：回顾性病例分析,于2000-06/2008-11在解放军第一八四医院泌尿外科完成。 对象：33例膀胱癌患者,男21例,女12例,平均年龄64岁。对照组为25例经胃肠镜活检无乙状结肠疾病史者。 方法：采用根治性膀胱全切、利用肛门括约肌控尿的Roux-y乙状结肠新膀胱术进行手术治疗膀胱癌患者,分析新膀胱引流管拔管前后血电解质、肌酐和尿素的变化,并对其中13例患者的贮尿囊黏膜于术前、术后36个月取材作病理学检查。对照组为25例无乙状结肠疾病史者乙状结肠黏膜。检测项目包括肠黏膜厚度及腺体数目。 主要观察指标：手术前、拔管前后电解质、肾功能和酸碱平衡、黏膜层厚度、腺体数目。 结果：30例患者术后血电解质、肌酐和尿素均保持在正常范围,拔管前后电解质、肌酐和尿素的变化差异无显著性意义,3例患者表现有轻度的酸中毒。对照组手术前后结肠黏膜镜下改变不明显,基本保持了正常的组织结构。手术组术后黏膜层厚度变薄[(577.6±169.4),(412.5±114.7) μm,P < 0.05],肠腺排列疏松,间质稀少,单位腺体数目减少[(26.4±3.5),(15.2±2.7)个/HP ,P < 0.05]。术后新膀胱内的肠绒毛逐渐萎缩,肠上皮细胞未见增生及恶性改变。 结论：Roux-y乙状结肠新膀胱替代后肠黏膜层厚度变薄,肠腺排列疏松,间质稀少,单位腺体数目减少,人体代谢无明显变化。     

Effects of a selective Y2R antagonist, JNJ-31020028, on nicotine abstinence-related social anxiety-like behavior, neuropeptide Y and corticotropin releasing factor mRNA levels in the novelty-seeking phenotype

An outbred rat model of novelty-seeking phenotype has predictive value for the expression of locomotor sensitization to nicotine. When experimentally naïve rats are exposed to a novel environment, some display high rates of locomotor reactivity (HRs, scores ranking at top 1/3rd of the population), whereas some display low rates (LRs, scores ranking at bottom 1/3rd of the population). Basally, HRs display lower anxiety-like behavior compared to LRs along with higher neuropeptide Y (NPY) mRNA in the amygdala and the hippocampus. Following an intermittent behavioral sensitization to nicotine regimen and 1 wk of abstinence, HRs show increased social anxiety-like behavior in the social interaction test and robust expression of locomotor sensitization to a low dose nicotine challenge. These effects are accompanied by a deficit in NPY mRNA levels in the medial nucleus of the amygdala and the CA3 field of the hippocampus, and increases in Y2R mRNA levels in the CA3 field and corticotropin releasing factor (CRF) mRNA levels in the central nucleus of the amygdala. Systemic and daily injections of a Y2R antagonist, JNJ-31020028, during abstinence fully reverse nicotine-induced social anxiety-like behavior, the expression of locomotor sensitization to nicotine challenge, the deficit in the NPY mRNA levels in the amygdala and the hippocampus, as well as result an increase in Y2R mRNA levels in the hippocampus and the CRF mRNA levels in the amygdala in HRs. These findings implicate central Y2R in neuropeptidergic regulation of social anxiety in a behavioral sensitization to nicotine regimen in the LRHR rats.     

Effect of methylphenidate treatment on appetite and levels of leptin,ghrelin, adiponectin,and brain-derived neurotrophic factor in children and adolescents with attention deficit and hyperactivity disorder

Objectives. We aimed to explore whether the use of methylphenidate relates leptin, ghrelin, adiponectin, and brain-derived neurotrophic factor (BDNF). In addition, the relationship between methylphenidate-related weight loss in attention deficit hyperactivity disorder (ADHD) patients and these biomolecules were evaluated. Methods. Thirty ADHD patients receiving methylphenidate and 20 healthy controls were included. Leptin, ghrelin, adiponectin, and BDNF levels were measured at baseline and after two-month treatment in both groups. Results. At baseline, leptin, ghrelin, adiponectin, and BDNF levels were similar in the ADHD and control groups. The most common adverse events occurring in the ADHD group after a 2-month treatment period included loss of appetite (70%) and weight loss (66.7%). A significant difference was found in body weight, BMI, and CGI scores of the ADHD patients after the treatment. While post-treatment ghrelin and adiponectin levels were significantly higher in the ADHD group, BDNF level was significantly lower. Post-treatment decrease in leptin levels was not significant. Conclusions. Leptin and BDNF were not associated with poor appetite and/or weight loss due to methylphenidate treatment. However, ghrelin and adiponectin might be biomolecules that play a role in underlying neurobiological mechanisms of methylphenidate-related appetite or weight loss.