Tau Content Research Articles

Comparative chemical, taste, and functional components in different tissues of giant grouper (Epinephelus lanceolatus)

ABSTRACTThe chemical composition, nutrition, and flavor components of various giant grouper tissues were determined. The muscle protein content was about 20%, and the muscle fat content was in the range of 3.9–6.4%, which is higher than that of most other groupers. The bone had the highest fat value (12.5–14.2%). The major nucleotide-related compound in the tissues was inosine monophosphate (IMP); whereas in the skin, adenosine monophosphate (AMP) was predominant. The predominant free amino acid (FAA) in the tissues was taurine (Tau), followed by arginine (Arg), lysine (Lys), and glycine (Gly). Tau content was higher in chin meat, and lower in bone. The total peptide content was in the range of 660–1,390 mg/100 g, which was much higher than that observed in other fish species. Muscle was rich in C16:0, C18:0, C18:1, and omega-3 highly unsaturated fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Taurine (Tau) restores β-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs β cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin.

Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggest that impaired insulin signaling is the major contributor in the development of Alzheimer’s dementia (AD), which is the most common type of senile dementia. In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days). Six groups of adult male Wistar rats were used: normal, D-gal, Met (500 mg/kg/day, p.o), and Saxa (1 mg/kg/day, p.o) control groups, as well as D-gal/Met and D-gal/Sax treated groups. Impaired learning and memory function was observed in rats treated with D-gal using Morris water maze test. Biochemical and histopathological findings also revealed some characteristic changes of AD in the brain that include the increased content of acetylcholine, glutamate, and phosphorelated tau, as well as deposition of amyloid plaques and neurofibrillary tangles. Induction of insulin resistance in experimentally aged rats was evidenced by increased blood glycated hemoglobin, brain contents of insulin and receptors for advanced glycated end-products, as well as decreased brain insulin receptor level. Elevation of oxidative stress markers and TNF-α brain content was also demonstrated. Met and Saxa, with a preference to Met, restored the normal memory and learning functions in rats, improved D-gal-induced state of insulin resistance, oxidative stress and inflammation, and ameliorated the AD biochemical and histopathological alterations in brain tissues. Our findings suggest that D-gal model of aging results in a diminishing of learning and memory function by producing a state of impaired insulin signaling that causes a cascade of deleterious events like oxidative stress, inflammation, and tau hyper-phosphorylation. Reversing of these harmful effects by the use of insulin-sensitizing drugs like Met and Saxa suggests their involvement in alleviation insulin resistance as the underlying pathology of AD and hence their potential use as anti-dementia drugs.

α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects.

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice.

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Influence of physical exercise on β-amyloid, α-synuclein and tau accumulation: an in vitro model of oxidative stress in human red blood cells.

A common pathological feature of neurodegenerative disorders (NDs), such as Alzheimer's (AD) and Parkinson's (PD) diseases, is the abnormal accumulation and misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ) and tau, in brain and in peripheral tissues too. Oxidative stress has been proved to be involved in NDs at various levels and, in particular, in such protein alterations, on the contrary physical activity is emerging as a counteracting factor in NDs. In the present work, the content of Aβ, α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) were compared before and after in vitrooxidative stress treatment. Total Aβ, α-syn and tau were quantified in RBCs (isolated from the subjects) by immunoenzymatic assays. Oxidative stress was induced by in vitro H₂O₂ administration to RBCs. H₂O₂ treatment was confirmed to significantly enhance ROS accumulation in RBCs. Total Aβ content in RBCs was lower in the ATHL subgroup with respect to the SED one. In the SED subgroup, but not in the ATHL one, total Aβ levels were increased by oxidative stress. Total α-syn content was lower in the ATHL subgroup with respect to the SED one and α-syn levels were increased by oxidative stress in both subgroups, with the percentage of increase higher in SED. Total tau content was comparable in both ATHL and SED and it was not affected by oxidative stress. Our data confirm previous findings evidencing that both oxidative stress and sedentary style contribute to aberrant folding and accumulation of NDs-related proteins, pointing to the importance of both anti-oxidant therapies and exercising in the prevention and treating of such diseases.

Ultrasonic characteristics and clinical significance of umbilical cord blood flow in acute fetal distress

ObjectiveTo study ultrasonic characteristics of umbilical cord blood flow in acute fetal distress and its correlation with umbilical artery blood gas parameters, oxidative stress parameters, neonatal brain injury and myocardial injury. MethodsThe pregnant women delivered in Department of Obstetrics of our hospital were chosen during the period from May 2012 to August 2015. The pregnant women with acute fetal distress were included in the distress group, and the healthy pregnant women with no acute fetal distress were included in the control group. The resistance index (RI), pulsatility index (PI) and systolic/diastolic (S/D) ratio of umbilical artery were measured at 24–30 weeks, 31–36 weeks and 37–41 weeks of pregnancy. After delivery, umbilical artery blood was taken for analysis of blood gas and determination of oxidative stress parameters. The venous blood of newborns was taken to measure the myocardial injury and brain injury parameters. ResultsAt 24–30 weeks, 31–36 weeks and 37–41 weeks of pregnancy, RI, S/D and PI in pregnant women of distress group were significantly higher than those in control group. The pH, contents of arterial partial pressure of oxygen, vitamin C, vitamin E, superoxide dismutase and glutathione peroxidase in umbilical artery blood in pregnant women of distress group was significantly lower than those in control group and negatively correlated with the umbilical artery RI, PI and S/D. The contents of partial pressure of carbon dioxide in artery, lactic acid and malondialdehyde in pregnant women of distress group were significantly higher than those in control group and positively correlated with the umbilical artery RI, PI and S/D. The contents of lactate dehydrogenase, hydroxybutyrate dehydrogenase, creatine kinase, creatine kinase-MB, S100B, neuron-specific enolase, creatine kinase-BB and Tau in newborns' venous blood in distress group were significantly higher than those in control group and positively correlated with the umbilical artery RI, PI and S/D. ConclusionsThe ultrasonic characteristics of umbilical cord blood flow in patients with acute fetal distress are increase of the resistance, reduction of blood flow, and significant reduction of ultrasonic parameters of RI, PI and S/D. The degree of hypoxia, oxidative stress, myocardial injury and brain injury can also be evaluated.

RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease.

To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3β silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.

Association Between Angiotensin Receptor Blockers and Longitudinal Decline in Tau in Mild Cognitive Impairment

We have previously shown that angiotensin receptor blockers (ARB) use is associated with improved cognitive function in those with mild cognitive impairment (MCI) and with lower amyloid and Tau content on autopsy studies.1,2 The impact of ARBs on cerebrospinal fluid (CSF) amyloid and tau biomarkers is unknown. We analyzed data from the longitudinal Alzheimer’s disease Neuroimaging Initiative (ADNI) to assess the impact of ARB use on CSF amyloid and Tau markers.

Structural Determinants of Tau Aggregation Inhibitor Potency

Small-molecule Tau aggregation inhibitors are under investigation as potential therapeutic agents against Alzheimer disease. Many such inhibitors have been identified in vitro, but their potency-driving features, and their molecular targets in the Tau aggregation pathway, have resisted identification. Previously we proposed ligand polarizability, a measure of electron delocalization, as a candidate descriptor of inhibitor potency. Here we tested this hypothesis by correlating the ground state polarizabilities of cyanine, phenothiazine, and arylmethine derivatives calculated using ab initio quantum methods with inhibitory potency values determined in the presence of octadecyl sulfate inducer under reducing conditions. A series of rhodanine analogs was analyzed as well using potency values disclosed in the literature. Results showed that polarizability and inhibitory potency directly correlated within all four series. To identify putative binding targets, representative members of the four chemotypes were added to aggregation reactions, where they were found to stabilize soluble, but SDS-resistant Tau species at the expense of filamentous aggregates. Using SDS resistance as a secondary assay, and a library of Tau deletion and missense mutants as targets, interaction with cyanine was localized to the microtubule binding repeat region. Moreover, the SDS-resistant phenotype was completely dependent on the presence of octadecyl sulfate inducer, but not intact PHF6/PH6* hexapeptide motifs, indicating that cyanine interacted with a species in the aggregation pathway prior to nucleus formation. Together the data suggest that flat, highly polarizable ligands inhibit Tau aggregation by interacting with folded species in the aggregation pathway and driving their assembly into soluble but highly stable Tau oligomers.

Changes in the hippocampal extracellular amino acid neurotransmitter of kindled rats by kainic acid

Objective To establish and evaluate the animal model for temporal lobe epilepsy kindled by kainic acid (KA)in rats,to observe the changes in glutamic amino acid (Glu),taurine amino acid (Tau),and γ-aminobatyric amino acid (GABA) of the extracellular fluid in the hippocampus of kindled rats,and to analyze the role of neurotransmitters in epileptogenesis.Methods In order to establish an animal model for temporal lobe epilepsy in rats,the characteristics of praxiological changes,electrophysiological changes,and ultrastructural examinations were observed.The contents of Glu,Tau,and GABA were detected in the hypppocampus by microdialysis combined with high performance liquid chromatography (HPLC).Results Typical seizures were observed in the models.Epileptic discharges,such as spike,slow,spike-slow,and sharp waves appeared in the electroencephalogram (EEG).Electron microscopic analysis of the hippocampal tissues revealed an increase of excitatory amino acid levels.The levels of Glu,Tau,and GABA were higher than groups that were injected with normal sodium (P ＜ 0.05).Conclusion Excitatory amino acids and inhibitory amino acids in the presence of epilepsy play important roles and is one of the main causes of seizure. Key words: Epilepsy; Kainic acid; Glutamic amino acid; γ-aminobutyric amino acid ; Taurine amino acid

2, 6-Diisopropylphenol Protects Against The Impairment of Learning-memory and Reduces The Hyperphosphorylation of Protein Tau Induced by Electroconvulsive Shock in The Depression Model Rats Whose Olfactory Bulbs Were Removed*

Protein Tau is a very unequal phosphoric microtubule associated protein,which affect the transport of substances in the axons of the neurons,whose phosphorylation is one of the key methods to regulate neuronal function.The hyperphosphorylation of protein Tau can damage the learning and memory of rats.The impairment of learning-memory induced by electroconvulsive shock in depressed rats is relevant to the function failure of glutamic acid signal system.The phosphorylation of protein Tau can be up-regulated by the individual stress level through the excitatory neurotransmission system.The mechanisms of 2,6-diisopropylphenol effect on the central nerve system relate to inhibiting the release of glutamic acid and the activity of NMDAR.And the 2,6-diisopropylphenol can protects against the impairment of learning-memory induced by electroconvulsive shock in depressed rats though inhibiting the excitotoxicty of glutamate.The rise of glutamic acid which induced by electroconvulsive shock in depressed rats can lead to the impairment of learning-memory through up-regulating the hyperphosphorylation of protein Tau? The 2,6-diisopropylphenol can protect against this process? This study explore the reversion of the 2,6-diisopropylphenol against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by electroconvulsive shock in depressed rats,in order to provide experimental evidence for neuropsychological mechanisms on improving learning and memory and the clinical intervention treatment.According to the design of factorial analysis,two intervention factors were set up: the electroconvulsive shock(two levels: no disposition;a course of electroconvulsive shock) and the 2,6-diisopropylphenol(two levels: 5 ml Saline was injected peritoneally;5 ml 2,6-diisopropylphenol was injected peritoneally by dosage of 100 mg/kg).Thirty-two adult depression model rats whose olfactory bulbs were removed were randomly divided into four experimental groups(n=8,in each group): group Ⅰ(5 ml 2,6-diisopropylphenol was injected peritoneally in the Sprague-Dawley rats by dosage of 100 mg/kg);group Ⅱ(5 ml 2,6-diisopropylphenol was injected peritoneally in the Sprague-Dawley rats by dosage of 100 mg/kg and giving a course of electroconvulsive shock);group Ⅲ(5ml Saline was injected peritoneally in the Sprague-Dawley rats);group Ⅳ(5 ml saline was injected peritoneally in the Sprague-Dawley rats and giving a course of electroconvulsive shock).The Morris water maze test started within 1 day after the course of electroconvulsive shock finished in order to evaluate learning-memory.The hippocampus was removed from rats within 1 day after the Morris water maze test finished.The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography.The content of Protein Tau which includes Tau-5(Total protein Tau),p-PHF1Ser396/404,p-AT8Ser199/202,p-12E8Ser262,GSK-3β1H8 and PP-2A in the hippocampus of rats was detected with Western blotting.The electroconvulsive shock and the 2,6-diisopropylphenol can induce the impairment of learning-memory in depressed rats,extending the evasive latency time and shortening the space exploration time.And both influences present subtract effect.The electroconvulsive shock can significantly up-regulate the content of glutamate in the hippocampus of depressed rats which was reduced by 2,6-diisopropylphenol.And both influences present subtract effect.The electroconvulsive shock and the 2,6-diisopropylphenol does not affect the total protein Tau and protein PP-2A in the hippocampus of rats.The electroconvulsive shock can up-regulate the hyperphosphorylation of protein Tau and the expression of GSK-3β1H8 in the hippocampus of depressed rats,which is reduced by 2,6-diisopropylphenol.And both influences present subtract effect.Our results indicate that the electroconvulsive shock up-regulates the content of glutamate in the hippocampus of depressed rats,which up-regulates the hyperphosphorylation of protein Tau through up-regulating the expression of GSK-3β1H8,and further induce the impairment of learning-memory in depressed rats.Wheareas,the 2,6-diisopropylphenol protects against the impairment of learning-memory and reduce the hyperphosphorylation of protein Tau induced by electroconvulsive shock in depressed rats through reducing the expression of GSK-3β1H8 and the content of glutamate in the hippocampus.

Expression pattern of Tau in the rat brain during pregnancy and the beginning of lactation

Pregnancy involves changes in brain function that implicate a re-organization in neuronal cytoskeleton. We analyzed the content of the microtubule associated protein Tau (65kDa isoform) and its phosphorylated form (PhosphoTau) in several rat brain regions throughout pregnancy and on day 2 of lactation by Western blot. In hypothalamus the content of Tau increased on days 2 and 18 of gestation compared with days 14, 21 and in lactation. PhosphoTau content increased throughout pregnancy. In preoptic area Tau content did not show significant changes throughout pregnancy or lactation, however, the content of PhosphoTau presented a decrease on day 21 of gestation. In hippocampus Tau content decreased on day 14 until day 21 compared with day 2 of gestation, however, in lactation day 2 the content of Tau increased meanwhile PhosphoTau content progressively increased throughout pregnancy. In frontal cortex Tau content decreased on day 21 of gestation compared with days 2, 14 and 18, with an increase in lactation, whereas PhosphoTau did not show significant changes. In cerebellum Tau protein decreased on days 14, 18 and 21 of pregnancy with an increase in lactation. PhosphoTau content increased throughout pregnancy and on day 2 of lactation. PhosphoTau/Tau ratio changes in each brain area along pregnancy and in lactation. Our data suggest that Tau expression and its phosphorylation pattern change in a tissue-dependent manner throughout pregnancy and the beginning of lactation in the rat brain.

O1‐07‐05: Paired helical filaments from Alzheimer's disease brains induce the intracellular accumulation of tau in aggresomes: Novel therapeutic approaches to prevent the propagation and spreading of tau pathology

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer's disease (AD) and tauopathies. The specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated, it propagates between neighboring neuronal cells, possibly spreading along axonal networks. In other words, misfolded aggregated tau protein released by degenerating neurons can mediate and spread toxicity to neighboring cells. We studied whether PHFs could be taken up by cells and promote the spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green-fluorescent protein tagged tau (GFP-Tau) were treated with isolated fractions of human AD-derived PHFs for 24 hours. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was made particularly evident by the perinuclear localization of aggregates and the re-distribution of vimentin intermediate filament networks and retrograde motor protein dynein. Furthermore, the content of Sarcosylinsoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. Exosome related mechanisms did not appear to be involved in the release of GFP-Tau from untreated cells. Paired helical filaments can mediate the spreading of pathological tau aggregation. Paired helical filament-mediated formation of aggresome-like bodies may be important in neurodegeneration. The evidence that cells can internalize PHFs leading to the formation of aggresome-like bodies opens new therapeutic avenues to prevent the propagation and spreading of tau pathology.

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology.

Differential Impact of REM Sleep Deprivation on Cytoskeletal Proteins of Brain Regions Involved in Sleep Regulation

Rapid eye movement (REM) sleep is involved in memory consolidation, which implies synaptic plasticity. This process requires protein synthesis and the reorganization of the neural cytoskeleton. REM sleep deprivation (REMSD) has an impact on some neuronal proteins involved in synaptic plasticity, such as glutamate receptors and postsynaptic density protein 95, but its effects on cytoskeletal proteins is unknown. In this study, the effects of REMSD on the content of the cytoskeletal proteins MAP2 and TAU were analyzed. Adult female rats were submitted to selective REMSD by using the multiple platform technique. After 24, 48 or 72 h of REMSD, rats were decapitated and the following brain areas were dissected: pons, preoptic area, hippocampus and frontal cortex. Protein extraction and Western blot were performed. Results showed an increase in TAU content in the pons, preoptic area and hippocampus after 24 h of REMSD, while in the frontal cortex a significant increase in TAU content was observed after 72 h of REMSD. A TAU content decrease was observed in the hippocampus after 48 h of REMSD. Interestingly, a marked increase in TAU content was observed after 72 h of REMSD. MAP2 content only increased in the preoptic area at 24 h, and in the frontal cortex after 24 and 72 h of REMSD, without significant changes in the pons and hippocampus. These results support the idea that REM sleep plays an important role in the organization of neural cytoskeleton, and that this effect is tissue-specific.

Short- and long-term treatment with estradiol or progesterone modifies the expression of GFAP, MAP2 and Tau in prefrontal cortex and hippocampus

AimsWe analyzed the effects of the short- and long-term administration of estradiol (E2) or progesterone (P4) after ovariectomy on the expression of MAP2, Tau and GFAP in prefrontal cortex and hippocampus. Main methodsSprague Dawley rats were ovariectomized and immediately treated with E2 or P4 for 2 or 18weeks. At the end of treatments, hippocampus and prefrontal cortex were excised, proteins were extracted and MAP2, Tau and GFAP were analyzed by Western blot. Key findingsMAP2 and Tau content was not modified by E2 in the prefrontal cortex. On the contrary, P4 decreased MAP2 content after a short-term treatment, while it increased that of MAP2 and TAU in this brain region after a long-term treatment. E2 increased MAP2 content in hippocampus. In this region, short-term administration of P4 increased that of MAP2. GFAP content was diminished after a long-term administration of P4 in hippocampus. SignificanceCurrent data emphasize the importance of short- and long-term sex steroid treatment on neuronal and glial cytoskeletal proteins expression.

Quantification of taurine and amino acids in mice single fibrosarcoma cell by microchip electrophoresis coupled with chemiluminescence detection

A method based on MCE coupled with chemiluminescence (CL) detection was developed for the determination of taurine (Tau) and amino acids including alanine (Ala), glycine (Gly), tryptophan (Trp), glutamic acid (Glu) and aspartic acid (Asp) present in mice single fibrosarcoma (S180) cells. Cell injection, loading, cytolysis, electrophoretic separation and CL detection were integrated onto a simple double-T microfluidic chip. The intracellular constituents were electrophoretically separated within 150 s. The CL detection was based on the enhancement effects of Tau and amino acids on the CL reaction of luminol with H(2)O(2) and Cu(2+). The average amounts of Tau, Trp, Gly, Ala, Glu and Asp in per S180 cell from a cell population were 4.73, 1.23, 2.65, 1.94, 1.61 and 1.99 fmol. Ten S180 cells were analyzed, and the contents of Tau, Trp, Gly, Ala, Glu and Asp in mice single S180 cells were found to be in the range of 1.78-8.84, 0.95-2.31, 1.08-6.87, 1.03-4.05, 0.84-2.61 and 0.82-3.68 fmol, respectively. This work demonstrates that MCE coupled with CL detection is a useful analytical tool that is simple, quick and highly sensitive for single-cell analysis.

Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases

BackgroundPhospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Sträussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals.MethodsThe profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3β and CDK5 in the brains were tested.ResultsThe contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3β transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events.ConclusionThese data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3β and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.

Dynamic changes of glycine and taurine in corpus striatum of rats with ischemia-reperfusion injury and effects of electroacupuncture

To investigate the dynamic changes of glycine (Gly) and taurine (Tau) in corpus striatum of rats with ischemia-reperfusion injury (IRI), and the regulation effect of electroacupuncture on them. Thirty SD rats were randomly divided into sham surgery group, model group, and treatment group. Rats in the sham surgery group were operated without ischemia. Rats in the model group and treatment group were operated to make model of cerebral IRI. The ischemia status lasts 1.5 h, and reperfusion was performed for 3.75 h. Rats in the treatment group were treated with electroacupuncture at Fengchi (GB 20). Neurologic deficit score (NDS) was used to evaluate the rats functions. Microdialysis and High Performance Liquid Chromatography technique were used to detect the changes of Gly and Tau in corpus striatum of rats. Contents of Gly and Tau increased at 1.5 h after ischemia. Them decreased to level as same as those rats in the sham surgery group after reperfusion. The content of Gly in the model and treatment group increased again at 2–2.5 h after reperfusion, and then decreased to the same level of the sham surgery group. There was a third increase of Gly content in the treatment group at 2.75 h after reperfusion. Electroacupuncture treatment could delay the decrease of Tau content after reperfusion, and make it increase at 1.5, 2 and 2.75 h after reperfusion. The peak appeared in the last time. NDS in the model and treatment group were more than that in the sham surgery group, and lowered at 5.25 h after surgery. Effects in treatment group was better than that in the model group (P<0.05). IRI makes contents of Gly and Tau in corpus striatum increase at a special time. Electroacupuncture treatment could increase contents of Gly and Tau at a special time after reperfusion, which maybe an important mechanism of protecting effects of electroacupuncture on the brain.