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- ArticleDucharme G, Lowe GC, Goutagny R, Williams S.PLoS One. 2012;7(1):e29754.Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic-polyribocytidilic acid (poly I:C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease.
- ArticleChen BC, Chou CF, Lin WW.J Biol Chem. 1998 Nov 06;273(45):29754-63.We have shown that, in murine J774 macrophages, binding of UTP to pyrimidinoceptors stimulates phosphoinositide (PI) breakdown and an increase in [Ca2+]i. In this study, UTP modulation of the expression of inducible nitric-oxide synthase (iNOS) was investigated. Although UTP alone had no effect, stimulation of J774 cells with a combination of UTP (10-300 microM) and LPS (0.1-3 microgram/ml) resulted in a potentiated increase in nitrite levels. In parallel, the amount of iNOS protein induced by LPS was also potentiated by UTP treatment. The UTP potentiating effect was attenuated by U73122, suggesting involvement of the downstream signaling pathways of phosphatidylinositide turnover. The tyrosine kinase inhibitor genistein inhibited both the LPS-induced nitrite response and the UTP potentiation. Conversely, two protein kinase C inhibitors, Ro 31-8220 and Go 6976, and a phosphatidylcholine-specific phospholipase C inhibitor, D609, inhibited LPS-stimulated nitrite induction, but did not affect the potentiating effect of UTP, which was also unaffected by pretreatment with phorbol 12-myristate 13-acetate for 8 h. Furthermore, the UTP-induced potentiation was abolished by BAPTA/AM or KN-93 (a selective inhibitor of Ca2+/calmodulin-dependent protein kinase (CaMK)). Nitrite potentiation and iNOS induction were prominent when UTP was added simultaneously with LPS, with the potentiating effect being lost when UTP was added 3 h after treatment with LPS. Pyrrolidinedithiocarbamate (3-30 microM), an inhibitor of NF-kappaB, caused a concentration-dependent reduction in the nitrite response to LPS and UTP. In electrophoretic mobility shift assays, LPS produced marked activation of NF-kappaB and AP-1, which was potentiated by UTP. LPS-induced degradation of IkappaB-alpha as well as the phosphorylation of IkappaB-alpha were also increased by UTP. Moreover, the UTP-potentiated activation of NF-kappaB and AP-1 and the degradation and phosphorylation of IkappaB-alpha were inhibited by KN-93. Taken together, these data demonstrate that nucleotides, especially UTP, can potentiate the LPS-induced activation of NF-kappaB and AP-1 and of iNOS induction via a CaMK -dependent pathway and suggest that the UTP-dependent up-regulation of iNOS may constitute a novel element in the inflammatory process.
- ArticleHe B, Wang L, Xu B, Zhang Y, Alzheimer’s Disease Neuroimaging Initiative.Neurosci Lett. 2021 05 29;754:135765.Whether the cerebrospinal fluid (CSF) biomarkers of amyloid-positive and amyloid-negative patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) are significantly different is still unknown. The purpose of this study is to compare the differences in CSF total tau, P-tau and Aβ42 in patients with amyloid-positive positron emission tomography (PET) and amyloid-negative PET, and to explore related risk factors in cognitive normal (CN), early MCI (EMCI), late MCI (LMCI) and AD. 558 participants (140 CN; 233 EMCI; 125 LMCI; 60 AD) were recruited in this study from the AD Neuroimaging Initiative (ADNI) database. The associations between CSF biomarkers were assessed by partial correlation analysis. The relations between significant variables were determined by multinomial logistic regression. Compared with amyloid-positive PET patients, patients with amyloid-negative PET had higher CSF Aβ42 and lower P-tau in the whole samples. The concentration of Aβ42 in the positive amyloid PET was significantly different in different groups, but not the negative amyloid PET (CN vs. LMCI; CN vs. AD; EMCI vs. AD, all P < 0.05). When amyloid PET was positive, a weak correlation was found between the levels of Aβ42 and P-tau only in CN group. However, a moderate degree of correlation between Aβ42 and P-tau was found in EMCI and LMCI when amyloid PET was negative. After covariates adjustment, CSF Aβ42 was significantly associated with EMCI [adjusted odds ratio (OR) = 0.99, 95 % confidence interval (CI) = 0.99-1.00, P = 0.02) and LMCI (adjusted OR = 0.99, 95 % CI = 0.99-1.00, P = 0.007)] in patients with negative amyloid PET, not in patients with positive amyloid PET. Our findings highlight that Aβ42 had strong correlations with other biomarkers and might help reduce risk of EMCI or LMCI in patients with amyloid negativity.
- ArticleBai X, Liu X, Li X, Li W, Xie A.Neurosci Lett. 2021 05 29;754:135879.OBJECTIVE: We aimed to estimate the role of vacuolar protein sorting 13C (VPS13C) gene single nucleotide polymorphism (SNP) rs2414739 variant in the risk of PD by meta-analysis.
METHODS: Five eligible case-control studies including 2796 PD cases and 4138 health controls involved in this meta-analysis. The fixed or random effect model was selected based on the heterogeneity of the included studies which detected by I2 and Q tests. The association between rs2414739 polymorphism and the risk of PD was evaluated using the pooled odds ratios (OR) and 95 % confidence interval (95 %CI). Sensitivity analysis was used to test the stability of the results. Funnel plot and Begg's test were employed to verified publication bias.
RESULTS: The results of our meta-analysis showed a significant correlation between VPS13C rs2424739 gene polymorphism and PD susceptibility in Allele model (A versus vs. G: OR = 1.14, 95 %CI = 1.05-1.23, p = 0.002), dominant model (GG + AG vs. AA: OR = 0.86, 95 %CI = 0.78-0.95, p = 0.004), heterozygote model (AG vs. AA: OR = 0.87, 95 %CI = 0.77-0.99, p = 0.04), homozygote model (GG vs. AA: OR = 0.76, 95 %CI = 0.60-0.96, p = 0.02). Surprisingly, we did not find a significant statistical difference between VPS13C rs2414739 polymorphism and PD risk in Chinese cohort in the regional stratified analysis.
CONCLUSIONS: This meta-analysis suggests that VPS13C rs2414739 polymorphism might act as a genetic predisposition factor for PD, whereas does not include Chinese population. - ArticleVaidya S, Shantanu PA, Tiwari V.Neurosci Lett. 2021 05 29;754:135751.BACKGROUND AND PURPOSE: Ongoing neuropathic pain is one of the most challenging clinical problems which have detrimental effects on a patient's life quality. Conventional therapies for chronic neuropathic pain majorly includes centrally acting analgesics. Unfortunately, the unceasing use of these drugs results in adverse effects, such as CNS in-coordination, respiratory depression and substance use disorder. DALDA ([D-Arg2, Lys4]-Dermorphin-(1-4)-amide), a peripherally acting opioid have been shown to possess potent analgesic activity without causing CNS toxicities in nerve-injured rats. However, the mechanism(s) underpinning DALDA induced-attenuation of ongoing neuropathic pain is yet to identify [1].
EXPERIMENTAL DESIGN: In this study, we have measured the in-silico ligand-receptor binding affinity of DALDA against potential inflammatory targets by utilizing glide module of schrödinger software. Effect of DALDA on oxido-inflammatory stress was evaluated in LPS-induced C6 glial cells. In-vitro studies were followed by the behavioral assessments, where effect of DALDA was measured in chronic constriction injured rats. To examine the effect of DALDA on dopaminergic neurotransmission, cerebrospinal fluid of nerve-injured rats was assessed using LC-MS/QToF (Liquid Chromatography-Mass spectrometry/ Quadrapole time of flight Analyzer).
RESULTS: DALDA has shown a good binding affinity with chemokine receptor type-2 (CCR2), chemokine CX3C receptor 1 (CX3CR1) and purinergic receptor (P2×4), major receptor subtypes involved in pain and inflammation. Findings from the in-vitro studies suggest that DALDA possesses potent anti-oxidant activity leading to inhibition of p38-MAPK pathway [1]. Moreover, the subcutaneous administration of DALDA leads to dose-dependent attenuation of thermal and mechanical hypersensitivity along with inhibition of neuroinflammatory mediators in serum and spinal cord of nerve-injured rats. Most importantly, DALDA treated neuropathic rats showed a preference for the DALDA-treated chamber, which was attenuated on pre-treatment with dopaminergic receptor antagonist, flupenthixol. LC-MS analysis further confirms the enhanced dopaminergic transmission in the brain of DALDA-treated neuropathic rats.
CONCLUSION: Our findings suggest that DALDA mediated attenuation of ongoing neuropathic pain may be associated with a decrease in spinal neuroinflammatory signalling and subsequent increase in the brain dopamine level; may serve a potential therapeutic for the treatment of ongoing neuropathic pain. - ArticleZhou J.Neurosci Lett. 2021 05 29;754:135899.The volitional movement of skeletal is controlled by the motor neuron at the site of neuromuscular junction (NMJ) where the retrograde signals are also passed back from muscle to the motor neuron. As the normal function of muscle largely depends on mitochondria that determine the fate of a skeletal muscle myofiber, there must exist a fine-controlled functional coupling between NMJ and mitochondria in myofibers. This mini-review discusses recent publications that reveal how spatiotemporal profiles of intracellular free Ca2+ could couple mitochondrial function with the activity of NMJ in skeletal muscle myofibers.
- ArticleGkanatsiou E, Sahlin C, Portelius E, Johannesson M, Söderberg L, Fälting J, Basun H, Möller C, Odergren T, Zetterberg H, Blennow K, Lannfelt L, Brinkmalm G.Neurosci Lett. 2021 05 29;754:135894.The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (Aβ) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Our aim was to investigate the Aβ peptide pattern in DS and AD brains to investigate differences in their amyloid deposition and aggregation, respectively. Cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (water soluble) and formic acid (water insoluble) fractions. Immunoprecipitation (IP) was performed using a variety of antibodies targeting different Aβ species including oligomeric Aβ. Mass spectrometry was then used to evaluate the presence of Aβ species in the different patient groups. A large number of Aβ peptides were identified including Aβ1-X, 2-X, 3-X, 4-X, 5-X, 11-X, and Aβ peptides extended N terminally of the BACE1 cleavage site and ending at amino 15 in the Aβ sequence APP/Aβ(-X to 15), as well as peptides post-translationally modified by pyroglutamate formation. Most Aβ peptides had higher abundance in AD and DS compared to controls, except the APP/Aβ(-X to 15) peptides which were most abundant in DS followed by controls and AD. Furthermore, the abundancies of AβX-40 and AβX-34 were increased in DS compared with AD. Aβ1-40, Aβ1-42, and Aβ4-42 were identified as the main constitutes of protofibrils (IP'd using mAb158) and higher relative Aβ1-42 signals were obtained compared with samples IP'd with 6E10 + 4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at amino acid 42. All Aβ peptides found in AD were also present in DS indicating similar pathways of Aβ peptide production, degradation and accumulation, except for APP/Aβ(-X to 15). Likewise, the Aβ peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility that treatment with clinical benefit in sporadic AD might also be beneficial for subjects with DS.
- ArticleConsonni M, Dalla Bella E, Bersano E, Lauria G.Neurosci Lett. 2021 05 29;754:135898.Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease marked by progressive loss of motor abilities. Approximately half of patents with ALS experience cognitive (ALSci) or behavioural impairment (ALSbi) during the course of the disease, with a small percentage developing overt frontotemporal dementia (FTD). ALSci and/or ALSbi can occur simultaneously with motor neuron degeneration or develop in advanced stages of the disease, but it can even precede motor involvement in some cases, namely in ALS patients meeting criteria for FTD. Despite clear evidence that cognitive/behavioural impairment may appear early in the course of ALS, no prominent deterioration seems to occur with disease progression. Longitudinal studies have failed to reach conclusive results on the progression of cognitive and behavioural involvement in ALS. This may be due to some structural limitations of the studies, such as attrition rate, practice effect, short-time interval between neuropsychological assessments, but it can also be due to the heterogeneity of ALS phenotypes. The objective of this review is to provide a comprehensive and critical analysis of results of longitudinal studies highlighting cognitive and behavioural domains mainly affected by neurodegeneration pointing out the determinants that might be associate with the development and worsening of frontotemporal symptoms in ALS. At this regard, older age, rapidly progressing ALS, bulbar-onset, advanced disease stages are among factors mainly associated with cognitive and behavioural involvement. Moreover, the progression of cognitive and behavioural deficits seems to be not directly related to the slope of motor disability, thus suggesting the independence of neuropsychological and motor functional decline in ALS. Cognitive and motor involvement may indeed present with distinct trajectories suggesting a differential vulnerability of motor and non-motor cortical networks. In this scenario, determining the progression of extra-motor involvement in ALS may help refine understanding of the clinical implications of cognitive and behavioural abnormalities, and provide clues to the aetiology of the disease.
- ArticleCui S, Lin H, Cui Y, Wen W, Cui X, Shen C, Mo H, Yang L, Bai S, Shi Y, Zhang R.Neurosci Lett. 2021 05 29;754:135851.Psychological stress is a common etiology among patients with lung cancer and serves as a potential indication of poor prognosis and advanced cancer clinical stage. Evidence indicates that depression is positively correlated with the evolvement of lung carcinoma. Nevertheless, the mechanisms underlying the effects of mental disorder on lung cancer have not been considerably and systemically explored. We hypothesized that mental disorder may affect the adjustment of the tumor microenvironment and immune cells. We used the chronic unpredictable mild stress (CUMS) procedure to induce depressed mice models and established tumor-bearing models of C57BL/6 J mice. Results revealed that the worsening of lung cancer was notably hastened in the CUMS + tumor group. Notably, the expression of PD-L1 in tumor issues increased in the tumor microenvironment, accompanied with a decline in the levels of CD8. On the basis of the date of tumor migration, our results indicated that MMPs and VEGF significantly increased after CUMS + tumor treatment. Thus, we demonstrated that modulation of the tumor microenvironment is pivotal for depression-promoted lung cancer migration.
- ArticleHan J, Liu Y, Song S, Wang Y, Zhang X, Chen H.Neurosci Lett. 2021 05 29;754:135853.Executive functions are thought to affect problematic eating behaviors in restrained eaters. While neurophysiological features of inhibitory control among restrained eaters in particular have been extensively investigated, considerably less is known about its influence on cognitive flexibility. The present study investigated the behavioral and neural correlates of food-related cognitive flexibility with event-related potentials (ERPs) associated in a task-switching paradigm among successful restrained eaters (SREs, n = 30) and unsuccessful restrained eaters (UREs, n = 32). Behavioral results revealed smaller switch reaction times among SREs than among UREs in both food-stimuli and neutral-stimuli tasks. ERP analyses indicated that neutral-switch trials, especially in UREs, displayed larger N2 amplitudes. In addition, SREs displayed larger P3 amplitudes in frontal, frontal-central, and central than UREs. P3 amplitude increased significantly during food-stimuli tasks compared to that during neutral-stimuli tasks. These results indicate that SREs possess better efficiency in enhanced cognitive transformation during the processing of target monitoring and conflict resolution. This is the first study to provide evidence for differences between SREs and UREs during task switching using ERP measures and reliance on different food-related processing strategies among SREs compared to UREs.
- ArticleSil S, Thangaraj A, Chivero ET, Niu F, Kannan M, Liao K, Silverstein PS, Periyasamy P, Buch S.Neurosci Lett. 2021 05 29;754:135863.Various research studies that have investigated the association between HIV infection and addiction underpin the role of various drugs of abuse in impairing immunological and non-immunological pathways of the host system, ultimately leading to augmentation of HIV infection and disease progression. These studies have included both in vitro and in vivo animal models wherein investigators have assessed the effects of various drugs on several disease parameters to decipher the impact of drugs on both HIV infection and progression of HIV-associated neurocognitive disorders (HAND). However, given the inherent limitations in the existing animal models of HAND, these investigations only recapitulated specific aspects of the disease but not the complex human syndrome. Despite the inability of HIV to infect rodents over the last 30 years, multiple strategies have been employed to develop several rodent models of HAND. While none of these models can accurately mimic the overall pathophysiology of HAND, they serve the purpose of modeling some unique aspects of HAND. This review provides an overview of various animal models used in the field and a careful evaluation of methodological strengths and limitations inherent in both the model systems and study designs to understand better how the various animal models complement one another.
- ArticleGao H, Fan S, Xie L, Hu S, Zhang Y.Neurosci Lett. 2021 05 29;754:135775.Astrocytes are activated after central nervous system (CNS) injury, such as spinal cord injury (SCI). Activated astrocytes can form glial scar to block nerve regeneration. Dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family, has been reported to contribute to the proliferation and migration of different types of tumor cells, including glioma. However, the functions of DSPP in reactive astrocytes after CNS injury remain unknown. In this study, starvation-serum stimulation model in astrocytes was conducted to explore this issue. Our results showed that DSPP expression was increased in reactive astrocytes comparing to normal ones. Meanwhile, up-regulation of DSPP was accompanied with PCNA and GFAP. To explore the role of DSPP in astrocytes, we overexpressed DSPP with recombinant GFP-DSPP plasmid and the results showed that overexpression of DSPP could promote the proliferation and migration of the cells, the important characteristics of reactive astrocytes. In addition, overexpression of DSPP obviously increased the activation of Akt/mTOR pathway in astrocytes. Taken together, we demonstrated that DSPP may play a key role in the proliferation and migration of astrocytes, suggesting that targeting DSPP might be a promising therapeutic strategy for treating CNS injury which characterized by glia scar formation.
- ArticleFukumoto Y, Todo M, Bizen H, Kimura D, Suzuki T.Neurosci Lett. 2021 05 29;754:135843.This study presents a novel approach for identifying neural substrates underlying the beneficial effects of motor imagery. For motor imagery, participants were instructed to imagine contraction of the left thenar muscle at 50 % maximal voluntary contraction (MVC). The participants then performed isometric contractions of the thumb and index finger at 50 % MVC as accurately as possible after motor imagery and without motor imagery. F-waves and oxygen-hemoglobin levels were examined with and without motor imagery relative to the resting condition. These data were analyzed using structural equation modeling. The degree of changes in the excitability of spinal motor neurons using F-waves during motor imagery may be modulated by inputs from the supplementary motor area. F-waves were analyzed with respect to persistence and the F-wave/maximum M-wave amplitude ratio. We found an association between precision pinch force control after motor imagery and spinal motor neuron excitability during motor imagery. The excitability of the supplementary motor area was not directly associated with precision pinch force control. However, spinal motor neuron excitability was adjusted by the supplementary motor area. Thus, the ability to perform precision pinch force control may be influenced by the supplementary motor area through the excitability of spinal motor neurons.
- ArticleGuo YZ, Ma YM, Zhang XP, Dong LD, Jing L, Zhang JZ.Neurosci Lett. 2021 05 29;754:135885.Brain edema is a major cause of death in patients who suffer an ischemic stroke. Diabetes has been shown to aggravate brain edema after cerebral ischemia-reperfusion, but few studies have focused on the heterogeneity of this response across different brain regions. Aquaporin 4 plays an important role in the formation and regression of brain edema. Here, we report that hyperglycemia mainly affects the continuity of aquaporin 4 distribution around blood vessels in the cortical penumbra after ischemia-reperfusion; however, in the striatal penumbra, in addition to affecting the continuity of distribution, it also substantially affects the fluorescence intensity and the polarity distribution in astrocytes. Accordingly, hyperglycemia induces a more significant increase in the number of swelling cells in the striatal penumbra than in the cortical penumbra. These results can improve our understanding of the mechanism underlying the effects of diabetes in cerebral ischemic injury and provide a theoretical foundation for identification of appropriate therapeutic modalities.
- ArticleDaini E, Secco V, Liao W, Zoli M, Vilella A.Neurosci Lett. 2021 05 29;754:135869.Intracellular Aβ (iAβ) expression, extracellular Aβ (eAβ) plaque formation and microglial reactivity are characteristic neuropathological events of Alzheimer's disease (AD) and have been detected in several transgenic mouse models of this disease. In this work we decided to investigate the early (2-7 months of age) development of these phenomena at both regional and cellular levels in 5XFAD mice, a severe transgenic mouse model of AD. We demonstrated that 1) Aβ pathology develops in many but not all brain regions, 2) iAβ is transient and almost always followed by eAβ in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aβ pathology and in several white matter regions, eAβ plaques can appear where no iAβ-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Aβ pathology development that is more prominent in females. Early iAβ is associated to the activation of microglia, while subsequent formation of eAβ plaques is associated with markedly increased density of microglial cells that acquire a characteristic clustered phenotype. Present analysis is relevant to set a reference for pathophysiological studies and to define specific targets for the test of therapeutic interventions in this widely used AD transgenic model.
- ArticleSalas-Leal AC, Salas-Pacheco SM, Gavilán-Ceniceros JAP, Castellanos-Juárez FX, Méndez-Hernández EM, La Llave-León O, Camacho-Luis A, Quiñones-Canales G, Romero-Gutiérrez E, Arias-Carrión O, Salas-Pacheco JM, Sandoval-Carrillo AA.Neurosci Lett. 2021 05 29;754:135901.Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.
- ArticleCygan A, Lisak D, Morzyński P, Bober M, Zawada M, Pazderski E, Ciuryło R.Opt Express. 2013 Dec 02;21(24):29744-54.We explore a cavity-enhanced spectroscopic technique based on determination of the absorbtion coefficient from direct measurement of spectral width of the mode of the optical cavity filled with absorbing medium. This technique called here the cavity mode-width spectroscopy (CMWS) is complementary to the cavity ring-down spectroscopy (CRDS). While both these techniques use information on interaction time of the light with the cavity to determine absorption coefficient, the CMWS does not require to measure very fast signals at high absorption conditions. Instead the CMWS method require a very narrow line width laser with precise frequency control. As an example a spectral line shape of P7 Q6 O₂ line from the B-band was measured with use of an ultra narrow laser system based on two phase-locked external cavity diode lasers (ECDL) having tunability of ± 20 GHz at wavelength range of 687 to 693 nm.
- ArticleGrober J, Zaghini I, Fujii H, Jones SA, Kliewer SA, Willson TM, Ono T, Besnard P.J Biol Chem. 1999 Oct 15;274(42):29749-54.Intestinal bile acid-binding protein (I-BABP) is a cytosolic protein that binds bile acids (BAs) with a high affinity. In the small intestine, its expression is restricted to the ileum where it is involved in the enterohepatic circulation of BAs. Using the human enterocyte-like Caco-2 cell line, we have recently shown that BAs increased I-BABP gene expression. To determine whether this regulation occurs in vivo, the effect of BA depletion or supplementation was studied in mice. A dramatic drop in I-BABP mRNA levels was observed in mice treated with the BA-binding resin cholestyramine, whereas an increase was found in animals fed with taurocholic acid. BAs are physiological ligands for the nuclear farnesoid X receptor (FXR). Both FXR and I-BABP are co-expressed along the small intestine and in Caco-2 cells. To determine the role of FXR in the regulation of I-BABP expression, the promoter of the human I-BABP gene was cloned. In Caco-2 cells, cotransfection of FXR and RXRalpha is required to obtain the full transactivation of the I-BABP promoter by BAs. Deletion and mutation analyses demonstrate that the FXR/RXRalpha heterodimer activates transcription through an inverted repeat bile acid responsive element located in position -160/-148 of the human I-BABP promoter. In conclusion, we show that FXR is a physiological BA sensor that is likely to play an essential role in BA homeostasis through the regulation of genes involved in their enterohepatic circulation.
- ArticleHashimoto S, Drevon CA, Weinstein DB, Bernett JS, Dayton S, Steinberg D.Biochim Biophys Acta. 1983 Nov 29;754(2):126-33.The influence of membrane cholesterol on the activities of acyl-CoA: cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase was examined in three microsomal subfractions (RNA-rich, RNA-poor, and smooth) that had been enriched with cholesterol by incubation with mixed lipoproteins from hypercholesterolemic rabbit serum. Acyl-CoA: cholesterol acyltransferase activity was significantly stimulated in the three subfractions, particularly in the RNA-rich microsomal component. 3-Hydroxy-3-methylglutaryl-CoA reductase, on the other hand, was suppressed (30%) in only one (RNA-poor) of the three microsomal subfractions, despite a 1.4-fold increase in the concentration of membrane cholesterol. An attempt was made to distinguish between an effect based exclusively on an increase in available cholesterol substrate and an activation of acyl-CoA: cholesterol acyltransferase in RNA-rich microsomes enriched with cholesterol. An experimental design was devised so that substrate cholesterol was provided in the form of heated smooth microsomes and acyl-CoA: cholesterol acyltransferase was provided as a separate preparation in the form of RNA-rich microsomes. Appropriate controls were carried out to test for transfer of cholesteryl ester between the two sets of particles. The results suggested that cholesterol enhanced acyl-CoA: cholesterol acyltransferase activity by serving both as a substrate and as a non-substrate modulator.
- ArticleNg VL, Herndon VL, Mendelson CR, Snyder JM.Biochim Biophys Acta. 1983 Nov 29;754(2):218-26.In the present study, the apolipoproteins associated with a purified surfactant fraction isolated from lung lavage of adult rabbits were characterized. Surfactant purity was assessed by the glycerophospholipid composition and by electron microscopic examination. The purified surfactant was delipidated and the apolipoproteins were analyzed by two-dimensional polyacrylamide gel electrophoresis. By use of this technique at least eight proteins or families of proteins were found to be associated with surfactant. Four of these apolipoproteins were families of proteins of 55-70, 29-36, 26-28 and 22-23 kilodaltons (kDa). All of these apolipoprotein families had acidic isoelectric points (pI less than or equal to 5.6), and were specifically bound to a Con A-Sepharose matrix, indicative that these apolipoprotein families are modified by oligosaccharide side-chains. The finding that neuraminidase treatment degraded the 29-36 kDa family is suggestive that this apolipoprotein family contains sialic acid residues. Three major proteins of 66, 43-45 and 35 kDa and a minor protein of 86 kDa were also observed. These proteins had isoelectric points in the more neutral range (pI 6.0-6.5). The 66 kDa protein (pI 6.4) had the same apparent molecular weight and isoelectric point as the major protein of delipidated rabbit serum and as purified rabbit albumin, which suggests that this protein is albumin. These findings are indicative that the apolipoproteins of surfactant are more numerous and complex than previously reported.