ANSTO :: Browsing by Author "Huang, XF"

Browsing by Author "Huang, XF"

Now showing 1 - 20 of 23

Activation of signal pathways and the resistance to anti-EGFR treatment in colorectal cancer
(Wiley-Blackwell, 2010-12-01) Chen, JZ; Huang, XF; Katsifis, A
Colorectal cancer is the third most common cancer with a 5-year survival rate of less than 10%. It is caused by alterations of multiple signal pathways which are affected by both genetic and environmental factors. In some cases, EGFR is important in the carcinogenesis of colorectal cancer suggesting anti-EGFR therapy may be a potential treatment option. However, in other cases it is not effective, which may be related to its down-stream targeted gene mutations. KRAS is highly emphasized in the literature but other mutations like Src, PIK3CA, and BRAF may also be important. Furthermore, obesity may decrease the effectiveness of anti-EGFR treatment as it increases the risk factors for colorectal cancer. Using next-generation sequencing technology, it may be possible to identify all gene mutations in an individual with colorectal cancer. Therefore, gene mutations affecting anti-EGFR therapy in colorectal cancer patients can be identified. © 2010, Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia
(Elsevier, 2007-01-30) Newell, KA; Zavitsanou, K; Jew, SK; Huang, XF
The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia. Therefore, in the present study we used quantitative autoradiography to investigate the binding of [3H]pirenzepine, [3H]AF-DX 384 and [3H]muscimol, which respectively label M1/4 and M2/4 muscarinic and GABAA receptors, in the PCC of schizophrenia and control subjects matched for age and post-mortem interval. The present study found that [3H]pirenzepine binding was significantly decreased in the superficial (− 24%, p = 0.002) and deep (− 35%, p < 0.001) layers of the PCC in the schizophrenia group as compared with the control group. In contrast, a dramatic increase in [3H]muscimol binding was observed in the superficial (+ 112%, p = 0.001) and deep layers (+ 100%, p = 0.017) of the PCC in the schizophrenia group. No difference was observed for [3H]AF-DX 384 binding between the schizophrenia and control groups. The authors found a significant inverse correlation between [3H]pirenzepine binding in the deep cortical layers and [3H]muscimol binding in the superficial layers (rho = − 0.732, p = 0.003). In addition, negative correlations were also found between age and [3H]pirenzepine binding in both superficial and deep cortical layers (rho = − 0.669 p = 0.049 and rho = − 0.778, p = 0.014), and between age of schizophrenia onset and [3H]AF-DX 384 binding (rho = − 0.798, p = 0.018). These results for the first time demonstrated the status of M1/M4, M2/M4 and GABAA receptors in the PCC in schizophrenia. Whilst the exact mechanism causing these alterations is not yet known, a possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia is suggested. © 2007, Elsevier
Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice
(Elsevier, 2015-09-05) Cheng, LC; Yu, YH; Zhang, QS; Szabo, A; Wang, HQ; Huang, XF
Epidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids (PUFA) is associated with the development of leptin resistance and obesity. We aim to examine the central effect of n-6 PUFA, arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose and lipid metabolism. We found that intracerebroventricular injection of ARA (25 nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro-inflammatory response in the hypothalamus. ARA also attenuated the effect of central leptin on hepatic glucose and lipid metabolism by reversing the mRNA expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG-CoA reductase). These results indicate that an increased exposure to central n-6 PUFA induces central cellular leptin resistance with concomitant defective JAK2-STAT3 and PI3K-Akt signaling. © 2015, Elsevier Ireland Ltd.
Bardoxolone methyl prevents fat deposition and inflammation in brown adipose tissue and enhances sympathetic activity in mice fed a high-fat diet
(MDPI, 2015-06-09) Dinh, CHL; Szabo, A; Yu, YH; Camer, D; Zhang, QS; Wang, HQ; Huang, XF
Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity. © 2015 by the authors; licensee MDPI, Basel, Switzerland
Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory
(Elsevier, 2015-06-03) Camer, D; Yu, YH; Fernandez, F; Dinh, CHL; Huang, XF; Szabo, A
High fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood–brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF diet-induced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus.© 2015, Elsevier Inc.
Bardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat diet
(Elsevier, 2015-09-05) Camer, D; Yu, YH; Szabo, A; Dinh, CHL; Wang, HQ; Cheng, LC; Huang, XF
High-fat (HF) diet-induced obesity is a major risk factor for the development of insulin resistance and hepatic steatosis. We examined the hypothesis that bardoxolone methyl (BM) would prevent the development of insulin resistance and hepatic steatosis in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC), HF (40% fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Glucose metabolism was assessed using a glucose tolerance test (GTT) and insulin sensitivity test (IST). Signalling molecules involved in insulin resistance, inflammation, and lipid metabolism were examined in liver tissue via western blotting and RT-PCR. BM prevented HF diet-induced insulin resistance and alterations in the protein levels of protein tyrosine phosphatase 1B (PTP1B), forkhead box protein O1 (FOXO1) and BDNF, and expression of the insulin receptor (IR), IRS-1 and glucose-6-phosphatase (G6Pase) genes. Furthermore, BM prevented fat accumulation in the liver and decreases in the β-oxidation gene, peroxisomal acyl-coenzyme A oxidase 1 (ACOX) in mice fed a HF diet. In the livers of HF fed mice, BM administration prevented HF diet-induced macrophage infiltration, inflammation as indicated by reduced IL-6 and signal transducer and activator of transcription 3 (STAT3) protein levels and TNFα mRNA expression, and increased nuclear factor-like 2 (Nrf2) mRNA expression and nuclear protein levels. These findings suggest that BM prevents HF diet induced insulin resistance and the development of hepatic steatosis in mice fed a chronic HF diet through modulation of molecules involved in insulin signalling, lipid metabolism and inflammation in the liver.© 2015, Elsevier Ireland Ltd.
Bardoxolone methyl prevents mesenteric fat deposition and inflammation in high-fat diet mice
(Hindawi, 2015-10-18) Dinh, CHL; Szabo, A; Camer, D; Yu, YH; Wang, HQ; Huang, XF
Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue. © 2015 Chi H. L. Dinh et al.
Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet
(Public Library of Science, 2014-03-27) Wu, YZ; Yu, YH; Szabo, A; Han, M; Huang, XF
A low-grade pro-inflammatory state is at the pathogenic core of obesity and type 2 diabetes. We tested the hypothesis that the plant terpenoid compound ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate obesity, obesity-associated inflammation and glucose intolerance in the high-fat diet-induced obese mouse model. Furthermore, we examined the effect of Rb1 treatment on central leptin sensitivity and the leptin signaling pathway in the hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily) for 21 days significantly reduced body weight gain, fat mass accumulation, and improved glucose tolerance in obese mice on a HF diet compared to vehicle treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB pathway molecules (p-IKK and p-IκBα) in adipose tissue and liver. In the hypothalamus, Rb1 treatment decreased the expression of inflammatory markers (IL-6, IL-1β and p-IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore, Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has potential for use as an anti-obesity therapeutic agent that modulates obesity-induced inflammation and improves central leptin sensitivity in HF diet-induced obesity. © 2014 Wu et al.
DHA prevents altered 5-HT1A, 5-HT2A, CB1 and GABAA receptor binding densities in the brain of male rats fed a high-saturated-fat diet
(Elsevier, 2013-07-01) Yu, YH; Wu, YZ; Patch, C; Wu, ZX; Szabo, A; Li, D; Huang, XF
Low levels of docosahexaenoic acid (DHA) have been linked to a number of mental illnesses such as memory loss, depression and schizophrenia. While supplementation of DHA is beneficial in improving memory and cognition, the influence of dietary fats on the neurotransmitters and receptors involved in cognitive function is still not known. The aim of this study was to investigate serotonin receptor (5-HT(1A) and 5-HT2A), cannabinoid receptor (CB1) and gamma-aminobutyric acid type A (GABA(A)) receptor binding densities in the brain of male rats fed a high-saturated-fat (HF) diet, as well as the effect of DHA supplementation on HF diet. Alterations of these receptors in the post-mortem rat brain were detected by [(3)H]-WAY-100635, [(3)H]-ketanserin, [(3)H]-CP-55,940 and [(3)H]-muscimol binding autoradiography, respectively. In the hippocampus, the 5-HT(1A), CB1 and GABA(A) receptor binding densities significantly increased in response to an HF diet, while in the hypothalamus, 5-HT(1A) and CB1 binding densities significantly increased in HF-fed rats. Importantly, DHA supplementation prevented the HF-induced increase of receptors binding density in the hippocampus and hypothalamus. Furthermore, DHA supplementation attenuated 5-HT2A receptor binding density in the caudate putamen, anterior cingulate cortex and medial mammillary nucleus, which was also increased in HF group. This study showed that an HF diet increased 5-HT(1A), 5-HT2A, CB1 and GABA(A) receptor binding densities in the brain regions involved in cognitive function and that dietary DHA can attenuate such alterations. These findings provide insight into the mechanism by which DHA supplementation ameliorates reduced cognitive function associated with an HF diet. © 2013 Elsevier Inc.
Dopamine transporter and D2 receptor binding densities in mice prone or resistant to chronic high fat diet-induced obesity
(Elsevier Science BV, 2006-12-15) Huang, XF; Zavitsanou, K; Huang, X; Yu, YH; Wang, HQ; Chen, F; Lawrence, AJ; Deng, C
This study examined the density of dopamine transporter (DAT) and D2 receptors in the brains of chronic high-fat diet-induced obese (cDIO), obese-resistant (cDR) and low-fat-fed (LF) control mice. Significantly decreased DAT densities were observed in cDR mice compared to cDIO and LF mice, primarily in the nucleus accumbens, striatal and hypothalamic regions. D2 receptor density was significantly lower in the rostral part of caudate putamen in cDIO mice compared to cDR and LF mice. © 2006, Elsevier Ltd.
Effects of typical and atypical antipsychotic drugs on rat brain muscarinic receptors
(Kluwer Academic Publishers-Plenum Publishers, 2007-02-01) Zavitsanou, K; Nguyen, VH; Han, M; Huang, XF
Quantitative in vitro autoradiography was used to examine changes in muscarinic M1/M4 and M2/M4 receptors (targeted with [3H]pirenzepine and [3H]AF-DX384 respectively), in rats treated with the typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic medications for a period of 36 days. Rats were sacrificed at either 2 h or 48 h after the last drug administration to examine immediate effects as well as the effects at 48 h after drug withdrawal. Haloperidol significantly increased [3H]pirenzepine binding in the dentate gyrus (37%) and in the CA1 region of the hippocampus (34%) in animals sacrificed 2 h after the last drug administration compared to controls. Similarly, clozapine significantly increased [3H]pirenzepine binding in dentate gyrus (29%) in rats sacrificed 2 h after the last drug administration compared to controls. Haloperidol decreased [3H]AF-DX384 binding in the basolateral nucleus of the amygdala (20%) in the rats sacrificed 48 h after the last drug administration compared to controls. These findings suggest that muscarinic receptors and limbic brain regions such as hippocampus and amygdala might represent common targets that mediate beneficial clinical effects of antipsychotic drugs. © 2007 Springer Science+Business Media, LLC
Immunohistochemical localisation of the NK1 receptor in the human amygdala: Preliminary investigation in schizophrenia
(Elsevier, 2006-09-30) Weidenhofer, J; Yip, J; Zavitsanou, K; Huang, XF; Chahl, LA; Tooney, PA
The amygdala has a role in the modulation of moods and emotion, processes that are known to be affected in people wi th psychiatric disorders such as schizophrenia and depression. The tachykinin NK1 receptor is known to be expressed in the amygdala. However to date, there is limited knowledge of the distribution of the NK1 receptor in this region. This study used immunohistochemistry to analyse the distribution of the NK1 receptor in fixed human amygdala tissue in control subjects with no history of psychiatric illness and matched subjects with a diagnosis of schizophrenia (n = 4 pairs). The NK1 receptor was observed sparsely distributed in cell bodies in all amygdaloid nuclei with the basolateral and lateral having a greater relative density of NK1 receptor-immunoreactive cell bodies than the other nuclei. Double labelling with antibodies to microtubule associated protein and the NK1 receptor revealed that the NK1 receptor is expressed by large pyramidal, small stellate and large bipolar neurons. Interestingly, the basal nucleus of Meynert, which is just dorsal to the amygdala, was observed to have a significantly higher relative density of NK1 receptor-immunoreactive cell bodies compared to any of the amygdaloid nuclei. Preliminary analysis of the density of NK1 receptor-immunoreactive cell bodies in the major amygdaloid nuclei and the basal nucleus of Meynert revealed no significant differences between schizophrenia and control subjects. Real-time PCR showed that the mRNA for both the short and long isoforms of the NK1 receptor was expressed at low levels in fresh frozen human amygdala tissue from control subjects and that this was not different in matched subjects with schizophrenia (n = 11 pairs). In conclusion, this study has demonstrated that the NK1 receptor is widely distributed in the amygdala, and has shown for the first time a high relative density of NK1 receptor-immunoreactive cell bodies in the basal nucleus of Meynert. © 2006, Elsevier Ltd.
Insulin decreases therapeutic efficacy in colon cancer cell line HT29 via the activation of the PI3K/Akt pathway
(Bentham Science Publishers Ltd, 2011-06-01) Chen, JZ; Katsifis, A; Hu, CH; Huang, XF
Obesity has been associated with both the carcinogenesis and poor prognosis of colon cancer, one of the leading causes of cancer-related death. Increased blood levels of insulin in obese subjects have been demonstrated to play a key role in carcinogenesis. It is also possible that insulin affects treatment efficacy, leading to poor prognosis. In this study, we demonstrated that insulin can increase HT29 colon cancer cell line resistance to cycloheximide and 5- fluorouracil induced cytotoxicity. This effect can be inhibited by the PI3K/Akt inhibitor Ly294002, indicating the important role of this pathway in the insulin-induced inefficacy of chemotherapy. The insulin-induced resistance to cycloheximide and 5-fluorouracil can be used in drug screening to overcome the inefficacy of chemotherapy in obesity-associated colon cancer. © 2011 Bentham Science Publishers
The molecular mechanisms underpinning the therapeutic properties of oleanolic acid, its isomer and derivatives for type 2 diabetes and associated complications
(Wiley, 2014-04-17) Camer, D; Yu, YH; Szabo, A; Huang, XF
Recent research has uncovered the molecular mechanisms responsible for the therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and derivatives. In particular, recent reports have highlighted the benefits of these compounds in the prevention and treatment of type 2 diabetes and associated life-threatening complications, such as nonalcoholic fatty liver disease, nephropathy, retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major concern since it is reaching global epidemic levels. Treatments targeting the signaling pathways altered in type 2 diabetes are being actively investigated, and OA and UA in natural and derivative forms are potential candidates to modulate these pathways. We will explore the findings from in vitro and in vivo studies showing that these compounds: (i) improve insulin signaling and reduce hyperglycemia; (ii) reduce oxidative stress by upregulating anti-oxidants and; (iii) reduce inflammation by inhibiting proinflammatory signaling. We will discuss the molecular mechanisms underpinning these therapeutic properties in this review in order to provide a rationale for the future use of OA, UA, and their derivatives for the prevention and treatment of type 2 diabetes and associated comorbidities. © 1999-2020 John Wiley & Sons, Inc.
Neuropeptide Y mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats
(Elseiver, 2006-06-03) Huang, XF; Deng, C; Zavitsanou, K
Using quantitative in situ hybridization, this study examined regional changes in rat brain mRNA levels encoding neuropeptide Y (NPY) following olanzapine, clozapine and haloperidol administration (1.2, 1.5 and 2.0 mg/kg, oral) for 36 days. The NPY mRNA expression levels and patterns were examined after the last drug administration at both time points enabling the measurement of immediate effect at 2 h and the effects after 48 h of drug administration. It was found that all these drugs had an immediate effect on NPY mRNA expression, while virtually all these changes normalized 48 h after the drug treatments. A similarity in altered NPY mRNA expression patterns was seen between the olanzapine and clozapine groups; however, haloperidol was very different. Olanzapine and clozapine administration decreased NPY mRNA levels in the nucleus accumbens, striatum and anterior cingulate cortex (from −60% to −77%, p < 0.05). Haloperidol decreased NPY mRNA expression in the amygdala and hippocampus (−69%, −64%, p < 0.05). In the lateral septal nucleus, NPY mRNA levels significantly decreased in the olanzapine group (−66%, p < 0.05), a trend toward a decrease was observed in the clozapine group, and no change was found in the haloperidol treated group. These results suggest that the different effects of atypical and typical antipsychotics on NPY systems may reflect the neural chemical mechanisms responsible for the differences between these drugs in their effects in treating positive and negative symptoms of schizophrenia. The immediate decrease of NPY mRNA levels suggests an immediate reduction of NPY biosynthesis in response to these drugs. © 2006, Elsevier Ltd.
Olanzapine differentially affects 5-HT2A (and 2C) receptor mRNA expression in the rat brain
(Elsevier Science BV, 2006-08-10) Huang, XF; Han, M; Huang, X; Zavitsanou, K; Deng, C
This study examined regional changes in rat brain mRNA levels encoding 5-HT2A and 5-HT2C receptors following chronic olanzapine treatment. The immediate effect (2 h after the last treatment) was a down-regulation of 5-HT2A receptor mRNA expression, predominantly in the hypothalamus, limbic system and striatum, while a rebound effect was observed 48 h later. 5-HT2C receptor mRNA expressions were decreased in the substantia nigra. Correlations between 5-HT2A receptor mRNA expression and total food intake, weight gain and energy efficiency were observed. © 2006, Elsevier Ltd.
Opposing short- and long-term effects on muscarinic M1/4 receptor binding following chronic phencyclidine treatment
(Wiley-Liss, 2007-05-01) Newell, KA; Zavitsanou, K; Huang, XF
Phencyclidine (PCP) is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Several studies have demonstrated that chronic NMDA receptor antagonist treatment in humans and animals can cause long-term behavioral changes that are reminiscent of negative and cognitive schizophrenia-like symptoms. The muscarinic cholinergic system, which is associated with cognitive functions, has been hypothesized to contribute to PCP's mechanism of action. No study, however, has examined the status of M1/4 receptors in the PCP model of schizophrenia. The aim of the present study was to investigate the effects of chronic (14 day) PCP treatment on mouse brain M1/4 receptors in the short term (1 hr and 24 hr) and long term (14 days) after last PCP administration. [3H]pirenzepine was used to target M1/4 receptors. In the short term following chronic PCP treatment, M1/4 binding was significantly increased in regions of the limbic system, caudate-putamen, cortex, and thalamus (ranging from 56% to 368%), compared with saline-treated mice. There were no differences in binding between mice treated with PCP for 14 days and sacrificed 1 hr or 24 hr after the final PCP treatment. In the long term following chronic PCP treatment, M1/4 binding was significantly decreased in all of the above-mentioned brain regions (ranging from 31% to 72%), except in the thalamus, which showed no change. These findings in the long-term group are similar to those reported in post-mortem studies of patients suffering from schizophrenia. © 2007, John Wiley & Sons, Inc.
Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice
(Elsevier, 2015-05-01) Cheng, LC; Yu, YH; Szabo, A; Wu, YZ; Wang, HQ; Camer, D; Huang, XF
The consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icv) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules and hepatic energy metabolism in C57BL/6 J male mice. We found that the icv administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling (JAK2-STAT3, PKB/Akt-FOXO1) and a pro-inflammatory response (TNF-α, IL1-β, IL-6 and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icv PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2) and lipogenesis (FAS and SCD1) in the liver of mice. Therefore, elevated central PA concentrations can induce pro-inflammatory responses and leptin resistance, which are associated with disorders of energy homeostasis in the liver as a result of diet-induced obesity. © 2015, Elsevier Inc.
Rapid cortico-limbic alterations in AMPA receptor densities after administration of PCP: implications for schizophrenia
(Elsevier, 2008-10) Zavitsanou, K; Nguyen, VH; Newell, KA; Ballantyne, P; Huang, XF
Phencyclidine (PCP), a non-competitive NMDA/glutamate receptor antagonist, is a psychotomimetic drug that produces a syndrome in normal humans that resembles schizophrenia. The present study investigated the mechanisms of PCP actions by examining the density of glutamate and muscarinic receptors in the rat brain 4 h after a single injection of PCP. We used receptor autoradiography and [H-3]MK801, [H-3]AMPA, [H-3]pirenzepine and [H-3]AFDX384 to target glutamate NMDA, glutamate AMPA and muscarinic M1 and M2 receptors, respectively. The major outcome from the present study was an overall decrease in levels of the glutamate AMPA receptor density (F= 14.5, d.f. = 1, p < 0.001) in the PCP treated rats. More specifically, PCP-treated animals displayed decreased AMPA receptor density in hippocampus CA1 (-16%), hippocampus CA2 (-25%), dentate gyrus (-27%), parietal cortex layers III-VI (-19%), central nucleus of the amygdala (-40%), and basolateral amygdala (-19%). Other brain regions examined were unaffected. PCP administration did not significantly affect glutamate NMDA, muscarinic M1 and M2 receptor density. The present study demonstrates the limbic system as the anatomical locus of alterations in AMPA receptor density after acute administration of PCP and may have implications for models of schizophrenia that focus on glutamatergic dysfunction in limbic cortical regions. © 2008, Elsevier Ltd.
Reduction of histamine H1 receptor binding induced by high-fat diet can be prevented by DHA and dietary fiber in specific brain areas of male rats
(Elsevier B.V., 2013-08-01) Wu, ZX; Yu, YH; Wu, YZ; Patch, C; Szabo, A; Huang, XF
High-fat (HF) diet and obesity are risk factors for a number of mental health problems including depression, cognitive dysfunction, dementia, and neurodegenerative diseases. Histamine H1 receptors (H1Rs) are involved in many of these conditions. This study examined H1R receptor binding density in the brain of male rats fed a high-saturated fat (HF) diet, as well as the effect of docosahexaenoic acid (DHA), galacto-oligosaccharide (GOS) and resistant starch (RS) supplementation of HF diet. Alterations of H1R expression in the post-mortem rat brain were detected by [3H]-pyrilamine binding autoradiography. We found that HF diet significantly decreased H1R binding densities in the substantia nigra (SN), caudate putamen (CPu), hypothalamic arcuate nucleus (Arc), ventral tegmental area (VTA), piriform cortex (Pir) and primary motor cortex (M1), compared with low-fat fed rats, and the suppression of receptor binding density ranged from 31% to 48%. Interestingly, supplementing the HF diet with 0.5% n-3 polyunsaturated docosahexaenoic acid (DHA) prevented reduction of H1R binding densities in the SN and CPu. Addition of galacto-oligosaccharide (GOS) and resistant starch (RS) to the diet blunted HF induced reduction of H1R ligand binding in the SN and Pir, respectively. In conclusion this study showed that HF diet can alter H1R binding densities in various brain regions, and many of these changes can be prevented by adding DHA, GOS or RS to the diet. © 2013 Elsevier Inc.

Browsing by Author "Huang, XF"

Results Per Page

Sort Options