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[The neurochemical characteristics of rats differing by their behavior in the emotional resonance test. Adenosine cyclic monophosphate in the brain structures of rats].

Content of cAMP in the frontal cortex (FC), hippocampus (HP), hypothalamus (HT) and amygdala (A) was determined in 20-month old male Wistar rats with different types of behaviour in "emotional resonance" test. Two groups of rats were selected, i.e., 1--animals which did not demonstrate ER phenomenon and 2--those which did not leave the light part of the chamber. Hippocampal content of cAMP was higher in group 1 than in group 2, in other brain structures no differences were detected. After acute immobilization stress cAMP level increased in FC, HT and A in both groups of animals. When the structures from the left and right hemispheres were analysed separately significant changes were revealed only in group 2 rats. Cross-correlations of cAMP levels between symmetrical FC, HP, HT and A were revealed in control animals of both groups. A number of new intra- and interhemispheric correlations appeared after stress, their pattern being dependent on behavioural type.

Analysis of Variance↗

Changes in CB1 receptors in motor-related brain structures of chronic relapsing experimental allergic encephalomyelitis mice.

Recent studies have examined the changes in the activity of cannabinoid signaling system in multiple sclerosis (MS), as a way to explain the efficacy of cannabinoid compounds to alleviate spasticity, pain, tremor and other signs of this autoimmune disease. In the present study, we have further explored this issue by examining density, mRNA expression and activation of GTP-binding proteins for the cannabinoid CB1 receptor subtype in several brain structures of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), a chronic model of MS that reproduces many of the pathological hallmarks of the human disease. CREAE animals were used at different phases in the progression of the disease (acute, remission and chronic) and compared to control mice. We observed several changes in the status of CB1 receptors that were region-specific and mainly circumscribed to motor-related regions, which is compatible with the symptomatology described for these animals that is preferentially of motor nature. We found a moderate decrease in the density of CB1 receptors in the caudate-putamen during the acute phase of CREAE. These reductions disappeared during the remission phase, but they were again observed, to a more marked extent, in the chronic phase. The same pattern for CB1 receptor density was observed in the cerebellum which, in this case, was accompanied by a progressive decrease in the capability of these receptors to activate GTP-binding proteins that was maximal in the chronic phase. The decrease in the density of CB1 receptors in the acute phase was also found in the globus pallidus but, in this case, the reduction was maintained during the further phases. No changes were observed in CB1 receptor-mRNA levels in any of the different regions examined. Finally, by contrast with the observations in motor structures, the status of CB1 receptors remained unaltered in cognition-related regions, such as the cerebral cortex and the hippocampus, during the different phases of CREAE. In summary, CB1 receptors were affected by the development of CREAE in mice exhibiting always down-regulatory responses that were circumscribed to motor-related regions and that were generally more marked during the acute and chronic phases. These observations may explain the efficacy of cannabinoid agonists to improve motor symptoms (spasticity, tremor, ataxia) typical of MS in both humans and animal models.

Animals↗

Brain structures and receptors involved in alertness.

Transitions between sleep and wakefulness are regulated by complex neurobiological mechanisms, which ultimately can be delineated as oscillations between two opponent processes--one promoting sleep and the other promoting wakefulness. The suprachiasmatic nuclei (SCN) provide temporal organization to the sleep-wake cycle through arousal mechanisms that oppose homeostatic drive or sleep. Assuming that individual cells in the SCN are competent circadian oscillators, it is important to understand how these cells communicate and remain synchronized with each other. Examination of the brain structures and receptors that are involved in alertness and the complex phenomena involved in regulation of the circadian sleep-wake cycle has provided evidence for an important role for the noradrenergic locus coeruleus (LC) system in the circadian regulation of alertness and performance. However, the broad interest in mechanisms underlying alertness is not solely to understand wakefulness but also to gain insight into how to maintain alertness and cognitive performance while awake. Few studies have attempted to link the role of a brain system in sleep-wake regulation with a role in cognitive performance during waking. We hypothesize that the dorsomedial hypothalamic nucleus (DMH) modulates the circadian rhythm of sleep and waking via projections to the LC. We propose a SCN-DMH-LC signalling pathway that may influence the activity of the LC and thereby a variety of central nervous system functions related to noradrenergic innervations, including alertness, vigilance, attention, learning and memory. The influence of sleep drive on the LC system may be important for our understanding of the deleterious effects of sleep loss on performance, and presents a logical target for developing new treatments to counteract impairments in alertness and performance due to poor quality sleep.

Animals↗

Brain structures selectively targeted by canine distemper virus in a mouse model infection.

Paramyxoviruses such as measles virus or canine distemper virus are etiological agents for acute and chronic encephalitis (measles inclusion body encephalitis, subacute sclerosing panencephalitis and chronic distemper encephalitis or old dog encephalitis). The mechanisms by which viral injury leads to neurological diseases have not yet been fully elucidated. We have developed an experimental model in mice in order to analyze the spatial and temporal distribution of canine distemper virus in the central nervous system. Cerebral target structures for viral replication were examined for the presence of viral material (proteins and mRNA) during the two stages of the biphasic disease. During the acute stage of infection all target areas could be identified by day 6 with a similar anatomical distribution in all the animals examined, which were either intracranially or intracerebroventricularly infected. Viral mRNA and proteins were selectively localized in certain brain structures such as the thalamus, hypothalamus, substantia nigra (pars compacta), locus ceruleus and raphe nuclei (dorsalis and centralis), and limbic system (hippocampus, septum, entorhinal and cingulate cortex, amygdala). The virus was apparently unable to replicate in cerebellum, striatum, a large part of cortex, or endothelial cells. During the subacute disease, viral material was no longer detectable except in a few structures such as hypothalamus up to 4-6 weeks after inoculation. After this time, all target structures were devoid of any labeling in spite of the occurrence of pathology (obesity, paralysis) during this viral quiescent phase. These results suggest that after the initial viral exposure, expression of viral genes in defined structures might disrupt central homeostasis and finally may lead to neurological or neuroendocrine diseases, even in the absence of the hallmarks of the virus.

Amygdala↗

Modulation of visual excitability cycles in some brain structures by high-frequency stimulation of raphe dorsal nucleus in cats.

The effect of high-frequency electrical stimulation of the raphe dorsal nucleus on the excitability cycles of the visual evoked potentials was studied. The evoked potentials to flash stimuli were recorded simultaneously in the lateral geniculate nucleus, centrum medianum, mesencephalic reticular formation, visual and associative parietal cortical areas. During stimulation of the raphe dorsal nucleus a facilitation of the visual excitability cycles in all structures studied occurred as compared to the cycles obtained before the stimulation. The analysis of the excitability cycles of the main two or three components of the visual evoked potentials revealed that the nonspecific structures were likely more involved in this activating effect than the specific ones. The data suggest that the raphe dorsal nucleus is involved in the modulation of the excitability of the visual afferent pathway and that this modulation after high-frequency stimulation of the nucleus is probably related to the increased excitability level in the nonspecific brain structures.

Animals↗

Optimization of 3-D MP-RAGE sequences for structural brain imaging.

An optimized MR sequence for structural three-dimensional brain scans is presented, giving good T(1) contrast and excellent white matter/gray matter segmentation. Modification of the usual linear phase encoding order to centric phase encoding restores the contrast loss, which usually occurs after magnetization preparation during the acquisition process when large volumes are imaged. The deleterious effects on the point-spread function are compensated by means of an appropriate k-space filter. RF coil inhomogeneities are corrected by means of shaped excitation pulses. High contrast-to-noise images of the entire brain with 1 mm isotropic resolution can be obtained in 12 min. The contrast-to-noise-ratio is about 100% higher than for sequences based on linear phase encoding.

Anatomy, Cross-Sectional↗

The effect of systemic circulatory arrest on the process of free-radical oxidation and on NO-synthase activity in the brain structures of rats of different behavioral types in an emotional resonance test: the acute effects.

Free radical-mediated processes and NO-synthase activity were studied in cerebral structures and blood serum of male Wistar rats with different types of behavior in emotional resonance test one hour after global ischemia induced by cardiac arrest. Oxidative stress accompanied by loss in NO-synthase activity was revealed in cerebral cortex after the ischemia. The oxidative stress was also evident in cerebellum and to a lesser extent in hippocampus. The majority of behavior-related biochemical differences were induced by cardiac arrest. These differences could be global or related to specific brain structures. Sometimes they became apparent in cerebral lateralization of biochemical indices.

Acute Disease↗

[Distribution of serotonin and its metabolites in the brain structures and immunosuppression in submissive mice].

The development of submissive behaviour in C57BL/6J mice in the sensory contact model was associated with an increase in the content of serotonin (5-HT) in the amygdala, hippocampus, dopaminergic nuclei A11, A10, A9, as well as in the caudate nucleus and hypothalamus after 10 and 20 days of confrontations compared to the controls. The level of 5-HT metabolite 5-hydroxyindolacetic acid (5-HIAA) was significantly higher in the most structures examined after 20 daily encounters as compared to animals with experience of 10 confrontations. The time course of submission over 10 or 20 days resulted in an increase of 5-HIAA/5-HT ratio in the midbrain nucleus raphe, nucleus accumbens, A9 and hypothalamus. In mice immunised on the 10th or 20th day of confrontations, the immune response inhibition was observed while its level remained unchanged after more prolonged confrontations (40 days). Thus, the experience of defeats during 10 days shown to be accompanied with an activation of 5-HT system in a number of the brain structures, produced immunosuppression. With increasing number of confrontations the ratio 5-HIAA/5-HT was decreased in the same structures and a tendency to the immune response elevation appeared.

Animals↗

Nature of the distribution of serotonin and a serotonin metabolite in brain structures and the development of immunosuppression in submissive mice.

Studies of C57BL/6J mice with acquired submissive behavior in a sensory contact model demonstrated increases in serotonin (5-HT) levels in the amygdaloid complex, hippocampus, the dopaminergic nuclei A11, A10, and A9, and in the caudate nucleus and hypothalamus, compared with controls, after 10 and 20 days of confrontations. Levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) in most structures were significantly higher after 20 days of confrontations than after 10 days. Increases in the 5-HIAA/5-HT ratio in the cervical nuclei of the midbrain, nucleus accumbens, A9, and hypothalamus as compared with controls were seen in mice with 10 and 20 days of confrontations. Immunization of mice on days 10 and 20 of confrontations showed suppression of immune responses as compared with controls, while immune measures reached control values by 40 days of experience of defeat. Thus, experience of 10 days of defeat led to immunosuppression on a background of activation of the 5-HT system in a series of brain structures: the cervical nuclei of the midbrain, the nucleus accumbens, and A9. As confrontations continued, there were decreases in the 5-HIAA/5-HT ratio on these structures, along with a tendency for immune responses to increase.

Animals↗

Ovulatory delay alters postnatal growth, behavior, and brain structure in rats.

To investigate the effect of a delay in ovulation on postnatal growth and development in resultant rat offspring, a 1-day ovulatory delay was induced by sodium pentobarbital, animals mated, and the offspring monitored. There were no differences between control and 1-day delayed offspring in the number of live or dead births, number of males or females, nor in the ratio of sexes. Delayed pups had a slightly lower birth weight, but then recovered to weigh more than controls by day 12. In the first two weeks post-parturition, delayed pups displayed an earlier ability to reorient themselves in a negative geotaxis test, but no differences by the righting reflex and reflex suspension tests. At postnatal day (pnd) 28, delayed pups exhibited decreased activity in a continuous corridor test, but no alterations in gait. At this time, the brains of delayed animals revealed thickening of cortical layers V plus VI. There were significant correlations between various developmental endpoints (body weight, negative geotaxis, continuous corridor activity, and gait) and the cortical layer thicknesses. The results indicate that ovulatory delay produces changes in brain cortical thickness, with correlative changes in growth and behavior. Although the mechanisms by which ovulatory delay alters postnatal development and brain structure are unknown, ovulatory delay may alter the uterine environment during early pregnancy.

Animals↗

[The effect of interoceptive stimulation on the protective barrier function of the stomach and on the malondialdehyde content of the gastric mucosa, blood serum and brain structures in rats].

The stomach chemo- and mechanoreceptors stimulation effect on the content of galactose, both general and that bound up with sulfated glycoproteins, in the stomach mucous membrane and blood serum as well as that of malon dialdehyd was studied in experiments on rats. The lipids peroxide oxidation and product concentration was also assessed in the trunk, diencephalon and forebrain. It was established that the chemoreceptors stimulation leads to a decrease in the content of galactose (general and that bound up with sulfated glycoproteins) and accumulation of malon dialdehyde in the stomach mucous membrane. The intensity of these changes depended on the quality of a chemical stimulator. The stomach mechanoreceptors stimulation caused an increase in the content of polymer glycoproteins and a decrease in the concentration of malon dialdehyde in the stomach mucous membrane. After the stimulation of interoceptors the brain structures showed an intensification of free radicals processes (diencephalon > trunk > forebrain), but the greatest content of malon dialdehyde was observed after the stomach chemoreceptors had been stimulated with hydrochloric acid solution.

Animals↗

[Effect of acute hypoxia on the EEG and neuronal pulse activity of various brain structures in rats].

The initial phase of hypoxia effect involves activation of the EEG (2000---6000 m) and unit impulse activity (7500--10 000 m). The 7500--10 000 m induced a change towards a predominant slow rhythm of the delta-type while the unit impulse activity gradually diminished, the cortical neurons displaying a higher hypoxia sensitivity and an earlier suppression than the cells of the hypothalamus and the medulla. In all phases of the hypoxia effect the EEG waves showed a greater sensitivity to the rapid peripheral signals than the unit impulse activity of the cortex and other brain structures.

Acute Disease↗

A method for very rapid determinations of catechols using ion-pairing reverse phase HPLC with electrochemical detection: effects of L-dopa treatment on the catechol content in various rat brain structures.

A simple and rapid method for determination of 12 catechols (9 endogenous and 3 internal standards, i.s.) using ion-pairing reverse phase HPLC with electrochemical detection is presented. This study basically concentrates on the importance of optimizing the mobile phase composition in isocratic systems where ordinary 25 cm X 4.6 mm i.d. columns are used. Mobile phase compositions for three different purposes are reported: 1) separation of 9 endogenous catechols, possibly occurring in the samples, and 3 i.s. in a moderately short retention time (tR) (L-DOPA, DOPEG, alpha-Methyldopa (alpha-MeDOPA, i.s.), Noradrenaline (NA), DOPAC, Adrenaline (A), Dihydroxybensylamine (DHBA, i.s.), Norsalsolinol (NS), Dopamine (DA), Epinine (EPI), Salsolinol (S) and Isoprenaline (ISO, i.s.) within 11 min), 2) ultra rapid separation of detectable endogenous catechols except L-DOPA (NA, DOPAC, A, DHBA (i.s.), NS and DA within 5.2 min and with S within 5.7 min) and 3) moderately fast separation of detectable endogenous catechols (L-DOPA, NA, A, DHBA (i.s.), NS, DOPAC and DA within 7.6 min and with S within 10 min). By balancing the pH, concentration of organic modifier (2-propanol) and pairing ion (1-heptanesulphonic acid) as well as preconditioning new columns with more packing material (Nucleosil 5 micron C18) and to high pressures (5000 psi) for 7 days, very fast separations with good baseline resolution between the peaks are possible. The method was applied on L-DOPA treated rats (100 mg/kg), where the catechol content was analysed in 7 different brain structures during the time course of synthesis and degradation (4 hours) of catechols from L-DOPA.

Animals↗

Morphochemical changes in brain structures in the course of chronic haloperidol treatment and the correction of these changes with tuftsin.

The systemic injection of haloperidol (4 wk, 0.5 mg/kg/d) caused the increase of protein concentration and content, and the activity level of aminopeptidase in the cytoplasm of the neurons of associated type (layer III). The nucleus of these cells decreased both in sizes and in the content of proteins. In the neurons of efferent-projectory type (layer V), the decrease of studied peculiarities as compared with control level was observed. Tuftsin (300 micrograms/kg/d) injection after chronic haloperidol treatment causes the restoring action on changed parameters in sensomotor cortex. In caudate nucleus, tuftsin influence caused further reduction of neuron's cytoplasmic area and significant reduction in protein content. The received results testify to the morphobiochemical heterogenity of investigated brain structures, which is displayed both in the case of haloperidol treatment and in the case of its correction by neuropeptide tuftsin. Chronic haloperidol administration to animals can develop a model of certain symptoms and syndromes of parkinsonism. Its most pronounced manifestation is an imbalance in the neuromediator systems, especially the dopaminergic one (Mettler and Crandall, 1959; Colls, 1984; Funk et al., 1986). The research was performed in conjunction with the physiologists, whose experiments have shown that after chronic haloperidol administration, changes in animal behavior are developed that are typical for bradikinesia, and the motor regimen of integration is disturbed (Popova and Kachalova, 1991; Dovedova and Povova, 1993). Regulatory drugs, especially the tetrapeptide tuftsin, seem to correct such disturbances.

Aminopeptidases↗

Chudley-McCullough syndrome: bilateral sensorineural deafness, hydrocephalus, and other structural brain abnormalities.

The Chudley-McCullough syndrome, an autosomal recessive condition first reported by Chudley et al. [1997], comprises profound sensorineural hearing loss and hydrocephalus secondary to an obstruction of the foramen of Munro. We describe two more sibs with this condition. One girl had sensorineural hearing loss and hydrocephalus due to obstruction of the foramen of Munro. Incidentally she was also found to carry a full mutation in the FMR1 gene. The older sister had profound sensorineural hearing loss and hydrocephalus not due to obstruction of the foramen of Munro; she also had callosal dysgenesis, gray matter heterotopia, cortical dysplasia, and cerebellar dysgenesis. Thus, the Chudley-McCullough syndrome may include hydrocephalus not necessarily related to obstruction of the foramen of Munro and other structural brain abnormalities.

Adolescent↗

Frontal cortex leads other brain structures in generalised spike-and-wave spindles and seizure spikes induced by picrotoxin.

Generaliszed spike-and-wave (SW) spindles (5-7 Hz) associated with myoclonic jerks precede the occurrence of regular spikes (2-3 Hz) associated with convulsive seizure induced by picrotoxin. SW spindles occur spontaneously in rodent and cat under some experimental conditions and are considered to be models of human generalised epilepsy. These spindles have been proposed as being led by a thalamic pacemaker. To examine this possibility in picrotoxin-induced SW spindles and seizure spikes, we recorded EEG using chronically implant unipolar electrodes during intravenous picrotoxin infusion in freely behaving rat. The 6 EEG signals were digitally sampled at 1000 Hz. Linear correlation, spectral, coherence and phase analyses were undertaken to determine time differences (TDs) between EEG channels and the brain structure leading seizure activity. One frontal cortex led all other structures during SW spindles. TD between SW spindles in the leading frontal cortex (Fr1) and the contralateral Fr1 was 3.6 + / - 0.5 msec. All ipsilateral structures (hippocampus, thalamus, amygdala, caudate nucleus and occipital cortex) were delayed by more than 3 msec from Fr1 (intralaminar thalamic nuclei - by 6.3 + / - 0.9 msec). TDs of SW spindles between subcortical regions were less than 1.5 msec. Similar relationships with slightly smaller TDs were found with spikes during convulsive seizure except TDs between frontal cortices did not significantly differ from zero. We suggest that seizure activity induced by picrotoxin is led by one Fr1 during SW spindles and by both frontal cortices working as one system during convulsive seizure.

Animals↗

Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure.

Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.

Adult↗

[Heat shock during the development of brain structures of Drosophila: the memory development in the l(1)ts403 mutant of Drosophila melanogaster].

The structures and functions of many genes are homologous in Drosophila and humans. Therefore, studying pathological processes in Drosophila, in particular neurogenerative processes accompanied by progressive memory loss, helps to understand the ethiology of corresponding human disorders and to develop therapeutic strategies. It is believed that the development of neurogenerative diseases might result from alterations in the functioning of the heat shock/chaperone machinery. In view of this, we used Drosophila mutant l(1)ts403 with defective synthesis of heat shock proteins for studying learning and memory in a test of conditioned courtship suppression following a heat shock given at different developmental stages. High learning indices were registered immediately and 30 min after training both in the intact controls and in flies subjected to different developmental heat shocks. This indicated normal learning and memory acquisition in the mutant. At the same time, memory retention (3 h after training) suffered to different extent depending on the developmental stage. The remote effects of heat shock given during the formation of the mushroom bodies indicated the important role of this brain structure in the memory formation. The observed memory defects may result from alterations both in mRNA transport and in the functions of molecular chaperones in the l(1)ts403 mutant.

Animals↗