Event-related synchronization and desynchronization of EEG during appraisal of threatening and pleasant visual stimuli in high anxious subjects

The 62-channel EEG was recorded while low (LA, n = 18) and high (HA, n = 18) trait-anxious subjects viewed sequentially presented neutral, threatening and pleasant IAPS stimuli. Event-related desynchronization (ERD) and synchronization (ERS) were studied in the delta, theta1, theta2, alpha1, alpha2, beta1, beta2, beta3, and gamma frequency bands. Between-group differences, related to stimulus emotionality, were linked to theta1 and theta2 bands. In the low theta at prefrontal sites in the test period of 100-700 ms after stimulus onset HA exhibited relative predominance of the left hemisphere in response to both threatening and pleasant stimuli, whereas LA yielded larger right than left hemisphere activity in response to all the three stimulus categories. In the upper theta band between group differences were associated with posterior cortical regions and the test period of 0-1000 ms after stimulus onset: HA exhibited the largest ERS to threatening, whereas LA prompted the largest ERS to pleasant stimuli. Finally, according to the ERD data, in the alpha1 band HA participants in comparison with LA revealed enhanced left hemisphere activation in response to all the stimulus categories. It is suggested that as it is indexed by theta-ERS relative predominance of the left hemisphere at prefrontal sites along with the largest bilateral activity of posterior cortical regions (i.e., enhanced higher order visual processing) to threatening stimuli could form the basis for general bias towards threatening information in HA at the very early stages of emotional processing.     

Reflection of the emotion manifestation in effects of evoked EEG synchronization and desynchronization

Event-related desynchronization (ERD) and synchronization (ERS) in response to neutral, positive and negative emotional IAPS stimuli were measured in narrow theta, alpha-1, alpha-2 and alpha-3 frequency bands in 22 healthy Ss. A high resolution 62-channel EEG was recorded while subjects viewed a sequence of pictures. The effects of valence discrimination related to hemispheric asymmetries are associated with increased theta and alpha-3 synchronization. Theta ERS revealed a significant valence by hemisphere interaction for anterior temporal leads in the time window of 100-700 ms after stimulus onset indicating a relatively greater right hemisphere ERS for negative and a left hemisphere ERS for positive stimuli in comparison to neutral those. In the alpha-3 band, negative stimuli induced a left hemisphere ERS increase (F7 site) in the time window of 800-1200 ms not observed for neutral and positive stimuli. The results obtained along with the earlier observations on EEG correlates of affective processing challenge the notion that effective anterior hemispheric asymmetries are reflected mainly in the wide alpha frequency band.     

Effect of alexithymia on the event-related theta-synchronization of human EEG during reception of emotional visual stimuli

The 62-channel EEG was recorded while control non-alexithymic (n = 21) and alexithymic (n = 20) participants viewed sequentially presented neutral, pleasant and unpleasant pictures and subjectively rated them after each presentation. The event-related synchronization (ERS) to these stimuli was assessed in the theta-1 (4-6 Hr) and theta-2 (6-8 Hz) frequency bands. The obtained findings indicate that alexithymia influences perception of only emotional stimuli. In the upper theta over anterior cortical regions alexithymia vs control individuals in response to both pleasant and unpleasant stimuli manifested decreased left hemisphere ERS in the early test period of 0-200 ms along with enhanced ERS in response to negative vs positive and neutral stimuli in the right hemisphere at 200-600 ms after stimulus onset. The findings provide the first EEG evidence that alexithymia construct, associated with a cognitive deficit in initial evaluation of emotion, is indexed by disrupted early frontal synchronization in the upper theta band that can be best interpreted to reflect disregulation during appraisal of emotional stimuli.     

Focus: Sex and Gender Health: Tobacco Smoking and the Resting Maternal Brain: A Preliminary Study of Frontal EEG

Tobacco smoking has been attributed to a wide range of detrimental health consequences for both women and their children. In addition to its known physical health effects, smoking may also impact maternal neural responses and subsequent caregiving behavior. To begin investigating this issue, we employed electroencephalography (EEG) to examine resting neural oscillations of tobacco-smoking mothers (n = 35) and non-smoking mothers (n = 35). We examined seven EEG frequency bands recorded from frontal electrode sites (delta, theta, alpha, alpha₁, alpha₂, beta, and gamma). While no between-group differences were present in high-frequency bands (alpha₂, beta, gamma), smokers showed greater spectral power in low-frequency bands (delta, theta, alpha, alpha₁) compared to non-smokers. This increased power in low-frequency bands of tobacco-smoking mothers is consistent with a less aroused state and may be one mechanism through which smoking might affect the maternal brain and caregiving behavior.     

Pre-stimulus spectral EEG patterns and the visual evoked response

The relationship between the latencies and amplitudes of the N1 and P2 components of the visual evoked potential (VEP) and the psychophysiological state of the brain immediately preceding the time of the stimulus has been investigated in 7 male subjects. Power spectral measures in the delta, theta, alpha and beta bands of the 1 sec pre-stimulus EEG were used to assess the brain state, and low intensity flashes, delivered randomly between 2 and 6 whole seconds, were used as the stimuli. Trials were ranked separately according to the relative amounts of pre-stimulus power in each EEG band and were partitioned into groups by an equal pre-stimulus spectral power criterion. Averaged EPs were computed from these groups and multiple regression analysis was used to relate pre-stimulus spectral power values to EP features. Five of the 7 subjects displayed consistent increases in N1-P2 amplitude as a function of increasing pre-stimulus relative alpha power. The between-subjects effect of pre-stimulus EEG on N1 latency was small, but was moderate for P2 latency (both significant). Both N1 and P2 latency were found to decrease with increasing amounts of pre-stimulus relative delta and theta power.     

Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors

The family of gamma-aminobutyric acid type A receptors (GABA(A)Rs) mediates two types of inhibition in the mammalian brain. Phasic inhibition is mediated by synaptic GABA(A)Rs that are mainly comprised of alpha(1), beta(2), and gamma(2) subunits, whereas tonic inhibition is mediated by extrasynaptic GABA(A)Rs comprised of alpha(4/6), beta(2), and delta subunits. We investigated the activation properties of recombinant alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs in response to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one (THIP) using electrophysiological recordings from outside-out membrane patches. Rapid agonist application experiments indicated that THIP produced faster opening rates at alpha(4)beta(2)delta GABA(A)Rs (beta approximately 1600 s(-1)) than at alpha(1)beta(2)gamma(2S) GABA(A)Rs (beta approximately 460 s(-1)), whereas GABA activated alpha(1)beta(2)gamma(2S) GABA(A)Rs more rapidly (beta approximately 1800 s(-1)) than alpha(4)beta(2)delta GABA(A)Rs (beta < 440 s(-1)). Single channel recordings of alpha(1)beta(2)gamma(2S) and alpha(4)beta(2)delta GABA(A)Rs showed that both channels open to a main conductance state of approximately 25 pS at -70 mV when activated by GABA and low concentrations of THIP, whereas saturating concentrations of THIP elicited approximately 36 pS openings at both channels. Saturating concentrations of GABA elicited brief (<10 ms) openings with low intraburst open probability (P(O) approximately 0.3) at alpha(4)beta(2)delta GABA(A)Rs and at least two "modes" of single channel bursting activity, lasting approximately 100 ms at alpha(1)beta(2)gamma(2S) GABA(A)Rs. The most prevalent bursting mode had a P(O) of approximately 0.7 and was described by a reaction scheme with three open and three shut states, whereas the "high" P(O) mode ( approximately 0.9) was characterized by two shut and three open states. Single channel activity elicited by THIP in alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs occurred as a single population of bursts (P(O) approximately 0.4-0.5) of moderate duration (approximately 33 ms) that could be described by schemes containing two shut and two open states for both GABA(A)Rs. Our data identify kinetic properties that are receptor-subtype specific and others that are agonist specific, including unitary conductance.     

急性高原低氧环境对不同情绪状态脑电功率的影响*

目的: 探讨急性高原低氧环境对不同情绪状态脑电功率的影响。方法:本研究为双因素多水平试验设计(氧气环境2个水平×情绪类型4个水平)。通过编写情绪图片诱导12名年龄在20～25岁之间的男性被试产生四类不同情绪:低效价低唤醒(LVLA)、高效价低唤醒(HVLA)、低效价高唤醒(LVHA)、高效价高唤醒(HVHA) ,分别近似于沮丧、轻松、恐惧、快乐四类情绪,并使用Brain Products 32导脑电采集设备采集不同情绪状态下的脑电信号;次日,采用常压低氧舱模拟4 300 m的高原低氧环境,同一批被试在低氧10 h 后使用相同试验范式采集脑电信号。对采集来的脑电信号进行功率谱分析(FFT),同时对额叶(F3\Fz\F4)脑电的五个频段(delta、theta、alpha、beta、gamma)进行两因素重复测量方差分析。结果:功率谱分析发现:急性低氧前后,四类情绪状态下alpha波的全脑分布差异主要集中在额叶、顶叶及部分颞叶;HVLA情绪状态下alpha波全脑分布差异最小。两因素重复测量方差分析结果发现:①delta、beta频段功率受氧气环境影响显著(P＜0.05),低氧环境下功率增强。②theta、alpha频段功率指标上,氧气环境和情绪类型交互作用显著(P＜0.05),低氧环境下除HVLA情绪状态外,theta、alpha频段功率皆出现了显著增强。③两因素对gamma频段影响都不显著(P＞0.05)。结论:在四类情绪状态下,氧气环境的变化对大脑活动的影响差异区域主要集中在额叶、顶叶及部分颞叶;低氧环境对沮丧、恐惧、快乐情绪状态有明显影响,低氧与情绪类型对于theta及alpha频段功率的改变具有协同作用。     

Background activity of the brain in healthy mental aging

The EEG mapping study tested age-related changes in power of EEG rhythms from delta to gamma ranges under healthy cognitive aging associated with preserved cognitive abilities and involvement in complex professional activity. 32 subjects of higher age group (HAG, mean age 65.1 +/- 1.18, 14 men and 18 women) and 33 subjects of lower age group (LAG mean age 22.1 +/- 0.38, 18 men and 15 women) participated in the study. Mean power of slow (delta, theta and alpha2) activity decreased and of fast activity (beta, gamma) increased as subject age increased. Compared to subjects of LAG subjects of HAG displayed a reduction in heterogeneity of EEG activity across recording sites. Centro-temporal gradients of power for frequency ranges from delta to beta2 and frontoparietal gradients and hemispheric asymmetry for alpha and beta1 rhythms were smoothed in subjects of HAG. These results suggest that observed age-related changes in baseline EEG may be the prerequisite for compensatory neural recruitment that may be associated as with allocation of more resources in cognitive processes so with reorganization of cortical networks including areas susceptible to physiological changes with aging.     

Event-related EEG changes preceding saccadic eye movements before and after dry immersion

Objectives of this work were to quantify antisaccade characteristics, presaccadic slow negative EEG-potentials, and event-related EEG frequency band power (theta, alpha1, alpha2, beta1, beta2 and beta3) changes (ERD) in healthy volunteers before and after 6-day simulated weightlessness (dry immersion).     

完全睡眠剥夺对大脑注意网络冲突效应和脑电样本熵的影响*

目的: 本研究分析睡眠剥夺对个体选择性注意网络冲突效应和脑电样本熵的影响,探讨睡眠剥夺对大脑注意网络的影响。方法: 25名健康受试者参与36 h完全睡眠剥夺试验。试验于当天9:00开始,于次日21:00结束,试验采用自身前后对照设计。受试者在睡眠剥夺前后分别完成注意网络任务,同步采集受试者的脑电图。用脑电样本熵算法分析脑电图的delta、theta、alpha、beta和gamma频率段的脑电复杂度并对比各频段脑电样本熵在睡眠剥夺前、后的变化。结果: 同睡眠剥夺前比较,睡眠剥夺后与受试者的注意网络冲突效应密切相关的反应时显著下降(P＜0.01),正确率显著增加(P＜0.01)。脑电样本熵分析发现在beta频率段,与注意网络冲突控制相关的脑电样本熵值在睡眠剥夺后明显增大(P＜0.01)。其余脑电频率段脑电样本熵未发现显著差异。结论: 表明完全睡眠剥夺后大脑的注意网络冲突效应降低,表明睡眠剥夺后执行冲突控制能力的下降。     

Does EEG activity during painful stimulation mirror more closely the noxious stimulus intensity or the subjective pain sensation?

Abstract

Background: Many researchers have tried to investigate pain by studying brain responses. One method used to investigate pain-related brain responses is continuous electroencephalography (EEG). The objective of the current study is to add on to our understanding of EEG responses during pain, by differentiation between EEG patterns indicative of (i) the noxious stimulus intensity and (ii) the subjective pain sensation.

Methods: EEG was recorded during the administration of tonic experimental pain, consisting of six minutes of contact heat applied to the leg via a thermode. Two stimuli above pain threshold, one at pain threshold and two non-painful stimuli were administered. Thirty-six healthy participants provided a subjective pain rating during thermal stimulation. Relative EEG power was calculated for the frequency bands alpha1, alpha2, beta1, beta2, delta, and theta.

Results: Whereas EEG activity could not be predicted by stimulus intensity (except in one frequency band), subjective pain sensation could significantly predict differences in EEG activity in several frequency bands. An increase in the subjective pain sensation was associated with a decrease in alpha2, beta1, beta2 as well as in theta activity across the midline electrodes.

Conclusion: The subjective experience of pain seems to capture unique variance in EEG activity above and beyond what is captured by noxious stimulus intensity.     

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background

EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.

Methodology

In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects.

Principal Findings

We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects.

Conclusions

We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.     

Coupling factor 1 from Escherichia coli lacking subunits delta and epsilon: preparation and specific binding to depleted membranes, mediated by subunits delta or epsilon

A procedure for the preparation of coupling factor 1 (F1) from Escherichia coli lacking subunits delta and epsilon is described. Using chloroform and dimethyl sulfoxide, we can isolate F1 containing only subunits alpha, beta, and gamma [F1(alpha beta gamma)] directly from membrane vesicles in 10-mg quantities. Pure and active subunits delta and epsilon were prepared from five-subunit F1 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After addition of these subunits, F1(alpha beta gamma) is as active in reconstituting ATP-dependent transhydrogenase as five-subunit F1. The ATPase activity of F1 (alpha beta gamma) is inhibited by subunit epsilon in a 1:1 stoichiometry to the same extent (approximately equal to 90%) and with the same affinity (Ki = 0.2-0.8 nM) as reported earlier [Dunn, S.D. (1982) J. Biol. Chem. 257, 7354-7359]. In the presence of either delta or epsilon, F1(alpha beta gamma) binds to F1-depleted membrane vesicles and to liposomes containing the membrane sector (F0) of the ATP synthase to an extent commensurate with the F0 content. The binding ratios epsilon/F1 (alpha beta gamma) and probably also delta/F1 (alpha beta gamma) are close to unity. The specific, delta- or epsilon-deficient F1.F0 complexes presumably formed show ATPase activities sensitive to subunit epsilon but not to dicyclohexylcarbodiimide, and no energy-transfer capabilities. Binding studies at different pH values suggest that F1-F0 interactions in the presence of both subunits delta and epsilon are similar to a combination of those mediated by delta or epsilon alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency component selection for an ECoG-based brain-computer interface.

The aim of the present study was to investigate the most significant frequency components in electrocorticogram (ECoG) recordings in order to operate a brain computer interface (BCI). For this purpose the time-frequency ERD/ERS map and the distinction sensitive learning vector quantization (DSLVQ) are applied to ECoG from three subjects, recorded during a self-paced finger movement. The results show that the ERD/ERS pattern found in ECoG generally matches the ERD/ERS pattern found in EEG recordings, but has an increased prevalence of frequency components in the beta range.     

Reduced Motor Cortex Deactivation in Individuals Who Suffer from Writer's Cramp

This study investigated the neuromagnetic activities of self-paced finger lifting task and electrical median nerve stimulation in ten writer''s cramp patients and fourteen control subjects. The event-related de/synchronizations (ERD/ERS) of beta-band activity levels were evaluated and the somatosensory cortical activity levels were analyzed using equivalent-current dipole modeling. No significant difference between the patients and control subjects was found in the electrical stimulation-induced beta ERS and electrical evoked somatosensory cortical responses. Movement-related beta ERD did not differ between controls and patients. Notably, the amplitude of the beta ERS after termination of finger movement was significantly lower in the patients than in the control subjects. The reduced movement-related beta ERS might reflect an impairment of motor cortex deactivation. In conclusion, a motor dependent dysregulation of the sensorimotor network seems to be involved in the functional impairment of patients with writer''s cramp.     

Molecular organization and pigment composition of R-phycoerythrin from the red alga Callithamnion rubosum

p3phycoerythrin is the major phycobiliprotein of Rhodophyta and endows these algae with the characteristic color. R-phycoerythrin purified from red alga Calithamnion rubosom is composed of four dissimilar polypeptide subunits, alpha, beta, gamma, and delta. In calibrated SDS gel electrophoresis their molecular weights are 21 000, 21 600, 31 000 and 33 000 daltons, respectively. The stoichiometry of the subunits in the native protein is 9 alpha: 9 beta: 2 gamma: 1 delta. R-phycoerythrin carries two covalently linked apoprotein red tetrapyrrol pigments: phycoerythrobilin (PEB) and phycourobilin (PUB). Chemical and spectroscopic data show that alpha subunit carries solely two PEB chromophores, beta subunit--3 PEB and 1 PUB groups, gamma subunit--3 PEB and 2 PUB groups and delta subunit--1 or 2 PEB and 1 PUB groups. The chromophore and polypeptide structure of R-phycoerythrin is mostly composed of all known phycobiliproteins of red and blue-green algae.     

Characteristics of interhemispheric EEG band power distribution in high anxiety individuals under emotionally neutral and aversive arousal conditions

The 62-channel EEG was recorded in control (CI, n = 21) and high anxiety (HA, n = 18) individuals under emotionally neutral (eyes closed, eyes open, and neutral videoclip) as well as under emotionally positive and aversive arousal conditions elicited by affective videoclips. In the present study the first three experimental conditions (eyes closed--eyes open--viewing emotionally neutral films) modeled increasing non-emotional arousal. Findings from this continuum show that in the HA individuals the lowest level of tonic arousal (eyes closed) was associated with stronger right-sided parietotemporal theta1 and beta1 activity. Group differences during cortical arousal increased by sensory stimulation (eyes open, neutral clips presentation) were marked only by persisting favored right hemisphere beta1 activity in high anxiety individuals. Under aversive arousal condition, attended by high intensity experience of emotions of anger, fear, disgust and anxiety, the HA subjects selectively desynchronized the right parietotemporal beta1 power which was initially higher in the control conditions. The obtained findings allow to suggest that peculiarities of right-sided parietotemporal EEG theta1 and beta1 activity in HA individuals under studied emotionally neutral and aversive arousal conditions point to overactivated withdrawal system in "checking" and "control" modes.     

Responses to tonic heat pain in the ongoing EEG under conditions of controlled attention

To confirm the existence of an ongoing electroencephalogram (EEG) pattern that is truly suggestive of pain, tonic heat pain was induced by small heat pulses at 1?°C above the pain threshold and compared to slightly less intense tonic non-painful heat pulses at 1?°C below the pain threshold. Twenty healthy subjects rated the sensation intensity during thermal stimulation. Possible confounding effects of attention were thoroughly controlled for by testing in four conditions: (1) focus of attention directed ipsilateral or (2) contralateral to the side of the stimulation, (3) control without a side preference, and (4) no control of attention at all. EEG was recorded via eight leads according to the 10/20 convention. Absolute power was computed for the frequency bands delta (0.5–4?Hz), theta (4–8?Hz), alpha1 (8–11?Hz), alpha2 (11–14?Hz), beta1 (14–25?Hz), and beta2 (25–35?Hz). Ratings were clearly distinct between the heat and pain conditions and suggestive for heat and pain sensations. Manipulation of attention proved to be successful by producing effects on the ratings and on the EEG activity (with lower ratings and lower EEG activity (theta, beta1, 2) over central areas for side-focused attention). During pain stimulation, lower central alpha1 and alpha2 activity and higher right-parietal and right-occipital delta power were observed compared to heat stimulation. This EEG pattern was not influenced by the manipulation of attention. Since the two types of stimuli (pain, heat) were subjectively felt differently although stimulation intensities were nearby, we conclude that this EEG pattern is clearly suggestive of pain.     

Chemical cross-linking studies of chloroplast coupling factor 1.

Cross-linking reagents have been used to link covalently adjacent subunits of solubilized spinach chloroplast coupling factor 1, which is a latent ATPase. 1,5-Difluoro-2,4-dinitrobenzene, dimethyl-3,3'-dithiobispropionimidate, and dimethylsuberimidate are able to form bridges of 3 to 11 A between amino groups, and hydrogen peroxide and the o-phenanthroline-cupric ion complex catalyze the oxidation of intrinsic sulfhydryl groups. The five individual subunit bands (alpha, beta, gamma, delta, and epsilon) and several new aggregate bands can be separated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The same four fastest moving aggregate bands, as characterized by their mobilities, migrate more slowly than the heaviest subunit band and appear with all of the cross-linkers employed. The subunit composition of the aggregate bands has been determined through the use of the reversible cross-linkers, dimethyldithiobispropionimidate, (o-phenanthroline)2Cu(II), and H2O2, and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which aggregates are separated in the first dimension, the disulfide cross-links are cleaved, and the individual subunits present in the aggregates are separated in the second dimension. The subunits are detected by Coomassie brilliant blue staining and by labeling some of the sulfhydryl groups of the gamma and epsilon subunits with radioactive N-ethylmaleimide. The results obtained indicate that the alpha and beta subunits can cross-link directly with each of the other subunits, that two beta subunits are adjacent, and that gamma epsilon, gamma epsilon 2, alpha delta, and beta delta aggregates are present. A minimal subunit stoichiometry consistent with these results is alpha 2 beta 2 gamma delta epsilon 2. A possible structural model of the coupling factor is derived from the data. Similar, but less extensive, experiments have been carried out with the heat-activated coupling factor (which is an ATPase); no differences in the spatial arrangement of subunits are detected from the two-dimensional gel electrophoresis analysis of the cross-linked aggregates.     

Chronic exposure to ammonia induces isoform-selective alterations in the intracellular distribution and NMDA receptor-mediated translocation of protein kinase C in cerebellar neurons in culture

Hyperammonemia is responsible for most neurological alterations in patients with hepatic encephalopathy by mechanisms that remain unclear. Hyperammonemia alters phosphorylation of neuronal protein kinase C (PKC) substrates and impairs NMDA receptor-associated signal transduction. The aim of this work was to analyse the effects of hyperammonemia on the amount and intracellular distribution of PKC isoforms and on translocation of each isoform induced by NMDA receptor activation in cerebellar neurons. Chronic hyperammonemia alters differentially the intracellular distribution of PKC isoforms. The amount of all isoforms (except PKC zeta) was reduced (17-50%) in the particulate fraction. The contents of alpha, beta1, and epsilon isoforms decreased similarly in cytosol (65-78%) and membranes (66-83%), whereas gamma, delta, and theta; isoforms increased in cytosol but decreased in membranes, and zeta isoform increased in membranes and decreased in cytosol. Chronic hyperammonemia also affects differentially NMDA-induced translocation of PKC isoforms. NMDA-induced translocation of PKC alpha and beta is prevented by ammonia, whereas PKC gamma, delta, epsilon, or theta; translocation is not affected. Inhibition of phospholipase C did not affect PKC alpha translocation but reduced significantly PKC gamma translocation, indicating that NMDA-induced translocation of PKC alpha is mediated by Ca2+, whereas PKC gamma translocation is mediated by diacylglycerol. Chronic hyperammonemia reduces Ca+2-mediated but not diacylglycerol-mediated translocation of PKC isoforms induced by NMDA.