Asymmetry of Characteristics of the Background Activity of Neurons of the Medial Vestibular Nucleus in Rats After Long-Term Vibration

Using computer analysis, we compared characteristics of the impulse background activity (BA) generated by neurons in the right and left medial vestibular nuclei (MVN) of the rats under control conditions and on the 5th, 10th, and 15th day with everyday 2-h-long sessions of vibrational stimulation. In the control group, the BA frequency generated by left-side MVN neurons was, on average, higher than that in the right MVN (23.6 ± 1.5 and 16.6 ± 1.7 sec^-1, respectively); other main characteristics of the BA demonstrated no significant internuclear differences. Vibrational influences of different durations induced complex significant laterally specific modifications of the level of regularity and dynamic indices of BA generated by neurons of the right and left MVN, of proportions of the cells with different types of distribution of interspike intervals (ISI), and of coefficients of variations of ISI. The mean frequency of background spiking in the right MVN increased about twofold (to 31.6 ± 2.2 sec^-1) after 10 days with vibration sessions, but dropped on the 15th day to 20.6 ± 1.7 sec^-1. In the left MVN, the mean BA frequency monotonically decreased, to 11.6 ± 1.0 sec^-1 after 15 days with vibration sessions. Therefore, chronic vibrational stimulation results in differential shifts of the characteristics of the BA generated by neurons of two MVN and in the formation of a new significantly asymmetrical pattern of such activity. Possible reasons for lateral asymmetry of the impulsation of MVN neurons and modifications of this asymmetry after long-term vibrational influences are discussed. We suppose that such an asymmetry can be one of the factors responsible for the development of motor and autonomic manifestations of vibration-induced motion sickness.     

Effect of Long-Lasting Vibration on the Impulse Activity of Neurons of the Inferior Vestibular Nucleus

We analyzed the impulse background activity (BA) of neurons of the inferior vestibular nucleus (IVN) of rats during exposure to long-lasting vibration (daily 2-h-long sessions). It was demonstrated that 5 days after the beginning of vibration stimulation, practically all main characteristics of the BA of IVN neurons changed significantly. In the studied neuronal group, 10 days after the vibration onset we observed an increase in the mean frequency of the BA and shifts in many statistical parameters of the BA, while after 15 days of vibration only significant modifications of dynamic characteristics of the BA of IVN neurons were manifested.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 32–38, January–February, 2005.     

Membrane and firing properties of avian medial vestibular nucleus neuronsin vitro

The intrinsic membrane and firing properties of medial vestibular nucleus (MVN) neurons were investigated in slices of the chick brainstem using intracellular recording and current injection. Avian MVN neurons fired spontaneous action potentials with very regular interspike intervals. The rapid repolarization of all action potentials was followed by an after-hyperpolarization. Intracellular injection of steps of hyperpolarizing current revealed both an inward rectification of the membrane potential during the step and a rebound depolarization following the offset of the step. In some neurons, the rebound depolarization resulted in bursts of action potentials. Steps of depolarizing current applied to spontaneously active neurons evoked increases in firing rate that were higher at the onset of the step than during the steady-state response. The relationship between current and firing rate was linear. The membrane and firing properties of avian MVN neurons were distributed continuously across the population of recorded neurons. These properties appear identical to those of rodent MVN neurons, suggesting that the composition and distribution of ion channels in the MVN neuronal membrane has been highly conserved across vertebrate species.Abbreviations MVN medial vestibular nucleus - VOR vestibulo-ocular reflex - AHP after-hyperpolarization     

Primary neurotransmitters and regulatory substances onto vestibular nucleus neurons.

This review article focused on the primary neurotransmitters involved in transmission from the otolith to the vestibular nucleus (VN), especially in relation to the neurotransmission to the VN neurons (gravity-sensitive neurons) activated by tilt stimulation. The medial vestibular nucleus (MVN) neurons were classified in 8 types (alpha-theta) according to the patterns in response to the clockwise and counterclockwise tilt-stimulations. The tilt-induced firing was inhibited by GDEE (a non-selective glutamate receptor antagonist) and/or atropine (a muscarinic receptor antagonist). Thus, glutamate and/or acetylcholine may serve as the primary neurotransmitters. This conclusion is supported by the previous findings that glutamate exists in the vestibular nerve and is released from the nerve besides the presence of glutamate receptor subtypes in the VN. In addition, acetylcholine induced atropine-reversible firing of MVN neurons, and the enzymes involved in acetylcholine synthesis/metabolism are also found in the VN. Furthermore, serotonin was found to inhibit the MVN neuronal activities via the 5-HT1A receptors. As such, the 5-HT1A agonist, tandospirone, may be effective in preventing and/or treating motion sickness and/or space sickness.     

Ethanol potentiates the effect of gamma-aminobutyric acid on medial vestibular nucleus neurons responding to horizontal rotation

Electrophysiological studies were performed to determine whether or not ethanol potentiates the inhibitory effects of gamma-aminobutyric acid (GABA) on medial vestibular nucleus (MVN) neurons responding to horizontal sinusoidal rotation using alpha-chloralose anesthetized cats. The MVN neurons were classified into types I, II, III and IV neurons according to the responses to the horizontal rotation of the animal placed on the turntable in directions ipsilateral and contralateral to the recording site. In addition, the effects of ethanol and GABA on type I neurons were also examined. Micro-osmotic application of ethanol up to 100 nA did not affect the spontaneous firing or the rotation-induced increase in firing of type I neurons. However, the inhibitory effects of GABA up to 50 nA on the rotation-induced increase in firing were potentiated during simultaneous application of ethanol up to 100 nA. This potentiated inhibition was blocked by iontophoretic application of bicuculline (25-150 nA) and picrotoxin (45-150 nA). These results suggest that ethanol potentiates the inhibitory effects of GABA on MVN type I neurons by acting on the GABA receptor and/or receptor-coupled chloride ion channel.     

急性低血压对前庭神经内侧核区谷氨酸和牛磺酸含量的影响

本实验用脑部微量透析法和高效液相色谱法观察急性失血诱发大鼠低血压时前庭神经内侧核(medial vestibular nucleus,MVN)内氨基酸类神经递质谷氨酸(glutamate,Glu)和牛磺酸(tautine,Tau)含量的变化,以了解MVN内这些氨基酸类递质是否参与血压的调节。实验观察到,正常血压大鼠MVN内Glu和Tau浓度在透析探针植入90 min后趋于稳定,此时 Glu的平均含量为(18．96±0．27)pmol／8 μl透析液,Tau的平均含量为(7．73±0．05)pmol/8μl透析液。动脉抽血1．5 ml诱发急性低血压时,同侧MVN区Glu含量增加(P<0．05),Tau含量减少(P<0．05)。用利多卡因(lidocaine)短时阻断前庭传入及用化学方法永久破坏单侧前庭器官后,动脉抽血1.5 ml使血压降低30％,同侧MVN内氨基酸类神经递质无明显改变。结果提示,急性失血引起的低血压可通过前庭器官影响MVN的活动,该区内氨基酸类递质可能参与这一活动的调节。     

Inhibition by enkephalin of medial vestibular nucleus neurons responding to horizontal pendular rotation

Electrophysiological studies were performed to determine whether or not enkephalin modulates the activities of medial vestibular nucleus (MVN) neurons responding to horizontal pendular rotation using alpha-chloralose anesthetized cats. The effects of microiontophoretically applied drugs were examined in type I and type II neurons identified according to responses to horizontal, sinusoidal rotation; type I and type II neurons showed an increase and decrease in firing with rotation ipsilateral to the recording site and vice versa with contralateral rotation, respectively. Iontophoretic application of enkephalin suppressed spike firing induced by rotation of the animals in type I neuron, but not in type II neuron. The spike firing induced by iontophoretically applied glutamate was also inhibited during the application of enkephalin. The inhibition by enkephalin of both rotation- and glutamate-induced firing was antagonized by naloxone which was given simultaneously. These results suggest that enkephalin acts on MVN type I neuron to inhibit transmission from the vestibule, thereby controlling vestibulo-ocular reflex.     

Analysis of the Neuronal Background Impulse Activity in the Rat Locus Coeruleus

Using several techniques of statistical analysis, we studied in detail the extracellularly recorded background impulse activity (BA) of neuronal elements of the rat locus coeruleus (LC). Impulse trains generated by most LC neurons were stationary and demonstrated different levels of regularity; a nonstationary type of BA was observed in 17% of the neurons under study. Statistical parameters of the BA generated by LC neurons showed a wide variability. Distributions of the BA interspike intervals (ISI) of most LC neurons were characterized by more or less expressed bimodality or polymodality. Serial correlation analysis of the ISI durations both in stationary and nonstationary spike trains allowed us to differentiate five main types of the dynamics of ISI successions in the BA of LC neurons.     

Contribution of REM sleep to Fos and FRA expression in the vestibular nuclei of rat leading to vestibular adaptation during the STS-90 Neurolab Mission

1. Electrophysical studies performed in ground-based experiments have shown that VN neurons respond to labyrinthine signals following stimulation of macular gravity receptors. Additional evidence indicates that VN neurons may also respond to extralabyrinthine signals of pontine origin, which occur during the PGO waves typical of REM sleep (Bizzi et al., 1964a, b; cf. also Pompeiano, 1967, 1970, 1974 for ref.). 2. In a previous study (Pompeiano et al., 2002) changes in Fos and FRA expression were used to identify the short-term (Fos) and the long-term (FRA) molecular changes which affect the VN neurons at different time points of the space flight. In particular, while Fos protein persists in the brain tissue only for a few hours (6-8 hrs) after its induction, FRA proteins, which can also be induced in the same experimental conditions, persist in the brain tissue for longer periods of time (i.e. from 12/24 hrs to days). 3. In order to relate the changes in gene expression which occurred in the VN during the space flight either to gravity changes or to REM sleep, we investigated in a recent study (Centini et al, 2006) the changes in Fos and FRA expression which occurred in different phases of the sleep-waking cycle, thus being indicative of the animal state. We could then compare the results obtained during the space lab Mission with those previously observed either in ground-based experiments during the physiological state of waking and slow-wave (SWS) or during neurochemically induced episodes of PS, as obtained after microinjection of appropriate agents in dorsal pontine structures of rats. 4. Our findings indicated that a waking state possibly associated with episodes of SWS, occurred at FD2 and FD14, i.e. at launch and after exposure of the animal to microgravity. It appeared also that at the reentry (R + 1) rather than at launch (FD2), an increase in Fos and FRA expression affected the noradrenergic LC neurons, as well as several related structures. These findings probably resulted from the acceleration stress, or immobilization stress as shown by the appearance of a starle reaction (or arrest reaction) which occurred after landing. This condition of stress was followed after landing by an increase in Fos and FRA expression which affected ventromedial medullary reticular structures, whose descending projections are involved in the suppression of postural activity during PS. Moreover, their ascending projections were likely to increase the FRA expression in the neocortex as well as in several regions of the limbic system, such as the dentate gyrus and the hippocampus, which lead to EEG desynchronization and the theta activity during PS. FRA expression affected also at the reentry pontine and diencephalic structures, such as the lateral parabrachial nucleus and the central nucleus of the amygdala, which are known to contribute to the occurrence of pontine waves and the related bursts of REM. 5. Observations made on the various components of the vestibular complex indicated that no Fos and FRA expression occurred in the LVN at the four different mission time points. However, an increase in Fos and FRA expression occurred particularly in the medial (MVN) and spinal vestibular nuclei (SpVN) at FD2 and at R + 1, i.e. 1 day after launch and 12-24 hours after landing, respectively. The pattern of FRA expression observed in the VN during the space flight was generally similar to that of Fos, except at the reentry, when FRA positive cells were observed throughout the whole SpVN, but not the MVN, which showed only a few labeled cells in its rostral part. In contrast to this finding, a prominent Fos expression was found not only in the SpVN, but also throughout the entire MVN. In this case the Fos labeling affected not only the caudal but also the rostral part of this structure, including the dorsal (MVePc) rather than the ventral aspect (MVeMc). Grounded on their different time of persistence, both Fos and FRA expression which occurred in the SpVe could be attributed to the increase in gravity force experienced during take-off and landing, while the Fos pattern which affected particularly the MVN soon after the reentry could additionally be attributed to the rebound episode of PS following the forced period of waking which occurred after landing and after the prolonged (12 days) exposure to microgravity. 6. The results of the present experiments provide the first molecular evidence that pontine activity sources producing rhythmic discharges of vestibulo-ocular neurons during REM sleep may substitute for labyrinthine signals after prolonged (12 days) exposure to microgravity, thus contributing to activity-related plastic changes in the VN leading to readaptation of the vestibular system to 1 G.     

Synaptic Plasticity in Medial Vestibular Nucleus Neurons: Comparison with Computational Requirements of VOR Adaptation

Background

Vestibulo-ocular reflex (VOR) gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD) at vestibular synapses.

Methodology/Principal Findings

Here we expressed this correlational learning rule in its simplest form, as an anti-Hebbian, heterosynaptic spike-timing dependent plasticity interaction between excitatory (vestibular) and inhibitory (floccular) inputs converging on medial vestibular nucleus (MVN) neurons (input-spike-timing dependent plasticity, iSTDP). To test this rule, we stimulated vestibular afferents to evoke EPSCs in rat MVN neurons in vitro. Control EPSC recordings were followed by an induction protocol where membrane hyperpolarizing pulses, mimicking IPSPs evoked by flocculus inputs, were paired with single vestibular nerve stimuli. A robust LTD developed at vestibular synapses when the afferent EPSPs coincided with membrane hyperpolarisation, while EPSPs occurring before or after the simulated IPSPs induced no lasting change. Furthermore, the iSTDP rule also successfully predicted the effects of a complex protocol using EPSP trains designed to mimic classical conditioning.

Conclusions

These results, in strong support of theoretical predictions, suggest that the cerebellum alters the strength of vestibular synapses on MVN neurons through hetero-synaptic, anti-Hebbian iSTDP. Since the iSTDP rule does not depend on post-synaptic firing, it suggests a possible mechanism for VOR adaptation without compromising gaze-holding and VOR performance in vivo.     

Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.     

Inhibition of adventitious root development in apple rootstocks by cytokinin is based on its suppression of adventitious root primordia formation

Cytokinin (CK) inhibits adventitious root (AR) formation in stem cuttings. Little is known, however, about the mechanism underlying the inhibitory effect. In this study, 2 mg l^?1 of exogenous 6‐benzyl adenine (6‐BA) was administered to 3 and 7‐day‐old apple rootstocks ‘M.26’ cuttings (3 and 7 days 6‐BA) by transferring them from a rooting medium containing indole‐3‐butanoic acid to the medium containing 6‐BA. Anatomical and morphological observations revealed that the exogenous application of 6‐BA inhibited primordia formation in the 3 days 6‐BA but not the 7 days 6‐BA group. The concentration of auxin (IAA), the ratios of IAA/CK and IAA/abscisic acid were lower in 3 days 6‐BA than in 7 days 6‐BA. Expression analysis of genes known to be associated with AR formation was also analyzed. In the 3 days 6‐BA group, high level of CK inhibited the synthesis and transport of auxin, as a result, low endogenous auxin level suppressed the auxin signaling pathway genes, as were other AR development and cell cycle related genes; all of which had an inhibitory impact on AR primordium formation. On the contrary, low CK level in the 7 days 6‐BA, reduced the inhibitory impact on auxin levels, leading to an upregulated expression of genes known to promote AR primordia formation. Collectively, our data indicated that 3–7 days is the time period in which AR primordia formation occurs in cuttings of ‘M.26’ and that the inhibition of AR development by CK is due to the suppression of AR primordia development over 3–7 days period after culturing in rooting medium.     

Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex

Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.     

Modulation of neuron activity of the midbrain periaqueductal gray matter influenced by monoaminergic brainstem structures

A study was done on base activity and changes in base activity (BA) of neurons in periaqueductal gray matter (PAG) during stimulation of monoaminergic structures of the brainstem: the nucleus raphe magnus (NRM), the locus coeruleus (LC), and the substantia nigra (SN), in rats anesthetized with hexenal (200 mg/kg). Three types of PAG neurons that differed in BA structure were identified. NRM, LC and SN stimulation changed BA only in type III neurons. Stimulation of these structures evoked an increase in BA frequency in 11.0–14.5%, and inhibition in 31.0–47.5% of type III neurons. Simultaneous stimulation of two structures led to a marked drop in intensity of effects. A depressing effect on BA was always detected if stimulation of one of the structures suppressed BA. Stimulation of two structures, with one being the NRM, was most effective. The role of PAG in the organization of the brain-stem component of the antinociceptive mechanism is discussed.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 24, No. 1, pp. 52–60, January–February, 1992.     

Effects of Immobilization Stress on the Background Impulse Activity of Locus Coeruleus Neurons

We studied in rats changes in the impulse background activity (BA) of locus coeruleus (LC) neurons after short- and long-term immobilization stress; distributions of LC neurons by the level of regularity of their BA, dynamics of spike trains, and pattern of histograms of interspike intervals (ISI) were taken into account. We also calculated the means of the main BA statistical indices. Both short- and long-lasting immobilizations resulted in drops in the mean frequency of background discharges of LC neurons to about half of the initial value. Two-hour-long immobilization evoked statistically significant shifts in the distribution of LC neurons by the level of regularity of their BA, while after longer (15 h) immobilization this distribution nearly returned to the initial pattern. Short-lasting immobilization exerted no significant effect on the dynamic characteristics of BA; statistically significant changes in this respect developed only after longer stress. After 15-h-long immobilization, we also observed a noticeable increase in the number of neurons with polymodal ISI distributions. Therefore, stress results in significant modifications of the temporal parameters of the BA of LC neurons; characteristics of the BA of these neurons should be considered neuronal correlates of the stress state.     

Temporal classification of Drosophila segmentation gene expression patterns by the multi-valued neural recognition method

In order to reconstruct the establishment of the body pattern over time in Drosophila embryos, we have developed automated methods for detecting the age of an embryo on the basis of knowledge about its gene expression patterns. In this paper we perform temporal classification of confocal images of expression patterns of genes controlling segmentation by means of a neural network based on multi-valued neurons (MVN). MVN are artificial neural processing elements with complex-valued weights and high functionality, which proved to be efficient for solving the image recognition problems. The results obtained by this method confirm its efficiency for image recognition and indicate that the method can detect characteristic features of expression patterns which mark their development over time.     

单侧迷路破坏后大鼠前庭神经内侧核区氨基酸含量的变化

本实验用脑部微量透析法和高效液相色谱法观察单侧迷路破坏(unilateral labyrinthectomy,经利多卡因或对氨基苯胂酸盐预处理以阻断单侧外周前庭器官)后大鼠同侧及对侧前庭神经内侧核(medial vestibular nucleus,MVN)区部分氨基酸(天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸)含量的变化,以了解前庭代偿的部分神经化学机制.实验观察到,对照组大鼠MVN区天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、牛磺酸和丙氨酸浓度分别为(6.15±0.59),(18.13±1.21),(33.73±1.67),(9.26±0.65),(9.56±0.77)和(10.07±0.83)pmol/8 μL透析样本.左侧中耳内灌注2%利多卡因后10 min,同侧MVN区天冬氨酸、谷氨酸含量立即减少(P＜0.05),牛磺酸含量增加(P＜0.05);对侧MVN区谷氨酸含量立即增加(P＜0.05),甘氨酸和丙氨酸含量减少;双侧核团间谷氨酸、甘氨酸和丙氨酸含量失衡.而用对氨基苯胂酸盐永久阻断单侧前庭器官2周后,同侧MVN区谷氨酸和丙氨酸含量减少,谷氨酰胺含量增高;对侧MVN区谷氨酸含量也减少;同侧MVN区谷氨酰胺含量明显高于对侧MVN区.结果提示,单侧迷路破坏后双侧MVN区氨基酸含量立即失去平衡,随着前庭代偿的进展,此差异减少,但是在前庭代偿后却出现双侧前庭核区谷氨酰氨的含量失衡,说明在前庭代偿过程中氨基酸含量变化起着重要作用.     

Changes in the background activity of neurons of the central gray substance when serotonin is applied to it or its synthesis is blocked

The changes in the background activity (BA) of neurons of the central gray substance upon the iontophoretic application of serotonin (ST) to them in a concentration of 1·10^–4 mole/liter, and following the blockage of its synthesis by pchlorophenylalanine (PCPA), were investigated in hexenal-anesthetized rats. The application of ST led to changes in the BA only in group III neurons, in which the BA was distinguished by continuous action potential generation. The application of ST elicited an increase in the frequency of the BA in 21.2% of such neurons, suppression in 45.5%, and the BA remained unchanged in 33.3% of the units. The identified changes in the BA in these neurons coincided with those which arose as the result of stimulation of the monoaminergic structures. When the application of ST was combined with stimulation of the locus coeruleus (LC), the substantia nigra (SN), and the nucleus raphe magnus (NRM), the suppression of the BA was intensified; however, when the LS and the SN were stimulated, the suppression was more pronounced than with stimulation of the NRM. The intensity of the suppressant effect of the NRM decreased after preliminary administration of PCPA, but it did not disappear completely, and the influences elicited by the LS and the SN intensified. The mechanisms of the serotoninergic control of the activity of the neurons of the central gray substance are discussed.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vo. 24, No. 2, pp. 169–177, March–April, 1992.     

Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent

Mevinolin (MVN) has been used clinically for the treatment of hypercholesterolemia with very good tolerance by patients. Based on epidemiological evidences, MVN was suggested strongly for the treatment of neoplasia. Early experimental trials suggested the mixed apoptotic/necrotic cell death pathway was activated in response to MVN exposure. Herein, the cytotoxic profile of MVN was evaluated, compared to the robust and frequently used anti-cancer drug doxorubicin (DOX), against breast (MCF-7), cervical (HeLa) and liver (HepG(2)) transformed cell lines. MVN was showed comparable results in cytotoxic profile with DOX in all tested solid tumor cell lines. In addition, the MVN-induced cytotoxicity was inferred to be multi-factorial and not solely dependent on p53 expression. It was concluded that molecular and genetic assessment of MVN-induced cell death would be useful for developing cancer therapeutic treatments.     

Comparative analysis of spontaneous unit activity of the cerebellum fastigial nucleus' neurons in different periods of vibration influence

In conditions of acute experiment on white rats anaesthetized with Nembutal (40 mg/kg, interperitonially) recording and analysis of spontaneous impulse activity of the fastigial nucleus' neurons in norm and after 5, 10 and 15 days of vibration influence on the organism were carried out. Distribution of the neurons was evaluated by the dynamics of neuronal current flow and the modality of the interspike interval hystograms, as well as the statistical parameters: the average discharge frequency and the coefficient of the interspike interval variation. It is shown that more significant changes in neuronal activity of fastigial nucleus cells are formed during the first 10 days of vibration influence. On the 15th day, there was a tendency towards return to control levels of the parameters under study.