Chronic exposure to high fat diet triggers myelin disruption and interleukin-33 upregulation in hypothalamus.

BACKGROUND: Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3-6 months to induce chronic obesity. RESULTS: The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1+-microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein. CONCLUSIONS: Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption.

Probing the Serotonin Transporter Availability Among Male Cigarette Smokers: A SPECT Study With [123I] ADAM.

OBJECTIVE: Genetic studies have suggested that the serotonin transporter (SERT) could be associated with cigarette smoking. However, evidence from neuroimaging is scarce. The aim of the present study was to examine the SERT availability among cigarette smokers by using single-photon emission computed tomography (SPECT). METHODS: Sixteen male smokers and 32 controls were enrolled. The SERT availability was measured by SPECT with a radiotracer, [I] ADAM, which is highly sensitive and specific to SERT. RESULTS: No significant difference in SERT availability was found between 2 groups in the midbrain (smokers: 2.12 ±â€Š0.70, nonsmokers: 2.13 ±â€Š0.63; P = 0.86), basal ganglia (smokers: 0.83 ±â€Š0.30, nonsmokers:0.90 ±â€Š0.39; P = 0.95), or thalamus (smokers: 1.14 ±â€Š0.41, nonsmokers: 1.20 ±â€Š0.38; P = 0.88). No significant association was found between the SERT availability, and either the breath carbon monoxide level or the score of the Fagerström Test for Nicotine Dependence. CONCLUSIONS: Whether the SERT availability in the brain is altered in smokers remains unclear.

Holistic Consideration of Patients with Schizophrenia to Improve Medication Adherence and Outcomes.

Although several algorithms have been applied to treat patients with schizophrenia, their clinical use remains still limited, because most emphasize the prescription of antipsychotics. A new algorithm with a more holistic approach to treating patients with schizophrenia, to be used before applying traditional prescribing guidelines, was thus proposed by an expert team of Taiwanese psychiatrists. In this algorithm, several important treatment tasks/modalities are proposed, including long-acting injection antipsychotics, shared decision-making, a case management system, compulsory treatment by law, community rehabilitation programs, the patients' feeling about their health care professionals (patients' behaviors) and their attitude/knowledge of their conditions/ illness. This study proposes that evaluating the medication adherence of patients can be determined by two key domains, namely patients' behaviors and attitudes. Based on different levels of their behaviors (X-axis) and attitude/knowledge (Y-axis), it is possible to categorize patients with schizophrenia into six subgroups, for which various different interventions, including the use of antipsychotics, could be applied and integrated. Further research is needed to assess the applicability of this treatment algorithm in clinical settings.

Tea-drinking habit among new university students: associated factors.

The habit of drinking tea is highly prevalent in Asian countries. The aim of this study was to investigate the prevalence of tea drinking and to explore the correlated factors on tea drinking among young new students in the university, using a validated self-reported questionnaire. This study was carried out with 5936 new students in a university in Taiwan. It comprised a self-administered structured questionnaire, including items related to personal and medical history, and lifestyle habits, using the Pittsburgh Sleep Quality Index (PSQI) and the 12-item Chinese Health Questionnaire (CHQ-12). Anthropometric measurements and laboratory tests were also performed. In total, 2065 (36.1%) students were in the tea-drinking group. Multiple logistic regression analysis showed the following factors were significant predictors of tea drinking: postgraduate students (p < 0.001), coffee drinking (p < 0.001), alcohol drinking (p < 0.001), minor mental morbidity (p = 0.009), poorer sleepers (p = 0.037), higher body mass index (p = 0.004), and sugar-sweetened beverage consumption (p < 0.001). Our data showed that the tea-drinking habit was correlated with higher body mass index, which was contrary to the findings of a previous study. In clinical practice, perhaps we could consider more tea-drinking-related factors when we suggest tea consumption.

Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X4 receptor expression in activated microglia.

Peripheral injection with a high dose of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, into animals with mild or moderate spinal cord injury (SCI) for 1 week can reduce spinal cord tissue loss and promote hindlimb locomotor recovery. A purinergic adenosine triphosphate (ATP) receptor subtype, P2X4 receptor (P2X4 R), has been considered as a potential target to diminish SCI-associated inflammatory responses. In this study, using a minipump-based infusion system, we found that intraspinal infusion with VPA for 3 days into injured spinal cord significantly improved hindlimb locomotion of rats with severe SCI induced by a 10-g NYU impactor dropping from the height of 50 mm onto the spinal T9/10 segment. The neuronal fibers in the injured spinal cord tissues were significantly preserved in VPA-treated rats compared with those observed in vehicle-treated animals. Moreover, the accumulation of microglia/macrophages and astrocytes in the injured spinal cord was attenuated in the animal group receiving VPA infusion. VPA also significantly reduced P2X4 R expression post-SCI. Furthermore, in vitro study indicated that VPA, but not the other HDAC inhibitors, sodium butyrate and trichostatin A (TSA), caused downregulation of P2X4 R in microglia activated with lipopolysaccharide (LPS). Moreover, p38 mitogen-activated protein kinase (MAPK)-triggered signaling was involved in the effect of VPA on the inhibition of P2X4 R gene expression. In addition to the findings from others, our results also provide important evidence to show the inhibitory effect of VPA on P2X4 R expression in activated microglia, which may contribute to reduction of SCI-induced gliosis and subsequently preservation of spinal cord tissues. © 2013 Wiley Periodicals, Inc.

The role of mitochondria-mediated intrinsic death pathway in gingerdione derivative I6-induced neuronal apoptosis.

Neuronal death induced by I6 displayed apoptotic characteristics but the precise mechanism has not been fully elucidated. In the present studies, I6 at 24 h after intraperitoneal administration significantly decreased the density of surviving neurons and increased caspase-3 activity in frontal cortex, suggesting that peripherally administered I6 may cross BBB to induce CNS toxicity. In rat embryonic primary cortical cells, I6-induced reduction of mitochondrial viability and neuronal apoptosis was inhibited by vitamin E. In addition, I6-induced reactive oxygen species (ROS) caused the disruption of mitochondria membrane potential (MMP), the release of cytochrome c, the activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP), resulting in activation of mitochondrial-mediated intrinsic death pathway. Pre-treatment with antioxidant vitamin E or N-acetylcysteine (NAC) completely abolished the I6-induced generation of ROS, loss of MMP, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), a mitochondrial uncoupler, significantly reduced I6-induced neuronal death as well as caspase-3 activation and PARP cleavage. These results suggest that I6 induces neuronal death by promoting intracellular ROS production to cause a loss of MMP that result in release of cytochrome c and activation of mitochondria-mediated intrinsic death pathway.

Loudness dependence of auditory evoked potentials (LDAEP) correlates with the availability of dopamine transporters and serotonin transporters in healthy volunteers-a two isotopes SPECT study.

RATIONALE AND OBJECTIVE: Although loudness dependence of auditory evoked potentials (LDAEPs) had been suggested as a noninvasive measure of central serotonin functions, recent studies suggest that LDAEP may be modulated by multiple neuromodulatory systems, such as dopamine. Here, we explore the relationship between LDAEP and dopamine and serotonin in the level of monoamine transporter availability. METHODS: Forty-nine healthy volunteers received LDAEP and single-photon emission computed tomography (SPECT) using [(99m)Tc] TRODAT and [(123)I] ADAM to approximate the availability of dopamine transporters (DATs) and serotonin transporters (SERTs). RESULTS: LDAEP was found to be positively associated with DAT, after adjusting for age and gender, and the log-transformed slope of loudness dependence at Cz was negatively associated with SERT. CONCLUSION: Our findings provide further evidence for the possible involvement of dopamine and serotonins in the genesis of LDAEP.

The functionality and economic costs of outpatients with schizophrenia in Taiwan.

The aims of this study were to investigate the economic costs of outpatients with schizophrenia in Taiwan, and to survey factors that influence the costs. The direct costs were defined as the costs associated with psychiatric services and other medical treatment. The indirect costs were estimated using the Human Capital Method. Patients' characteristics, including sex, age, duration of education, duration of illness, frequency of hospitalization, type of antipsychotic medication, severity of extrapyramidal side effects caused by antipsychotic medication, and global functions, were used to estimate the costs. The average annual total cost was approximately US$16,576 per patient. The direct and indirect costs were 13% and 87% of the total costs, respectively. Among the direct costs, folk therapy ranked third, just behind prescription drugs and acute ward hospitalization. The productivity loss of both the patients and their caregivers was the major component of the indirect costs. The patient's age and global functions had a significantly negative relationship with the direct costs. The severity of extrapyramidal side effects, type of antipsychotic medication, and the patient's illness duration correlated positively with the indirect costs, while the patient's global function correlated negatively with the indirect costs. Overall, the indirect costs of treating schizophrenia were higher than the direct costs. Improving patients' functionality and decreasing caregivers' burden are essential to reducing costs.