Transgenerational consequences of acute antenatal stress in pregnant rats

The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed.     

The influence of cortical lesions on penicillin induced convulsive activity in the awake rat

1. Experiments were performed to investigate the effects of cortical lesions on convulsive behaviour. Rats were lesioned in the left motor or sensory cortex by aspirating cortical tissue 2 to 3 months prior to the elicitation of convulsions. Convulsions were induced in the awake rats by the GABA antagonist Na-penicillin (Na-PCN) which was applied into the superficial layer of the foreleg field of their right motor cortex. Convulsive activity was recorded by means of the EEG. 2. The time courses of convulsive cortical activity were similar in the animals without or with a cortical lesion. Generalized seizures belonged to the tonic-clonic type in both intact and lesioned rats. 3. The early period of convulsive activity was described by the time to the onset (latency) of the first convulsive potential, jerk and seizure, and by the mean repetition rate of jerks during the first ten minutes, and the duration of the first generalized seizure. None of these parameters was significantly affected by a cortical lesion. 4. The median duration of the convulsive activity in intact animals was 162 min. In rats with a lesion in the sensory cortex it raised to more than 540 min while a lesion of the motor cortex increased the median duration to more than 273 min. The differences between intact and lesioned rats were significant (p less than 0.01 and p = 0.05, respectively). 5. The median time to the onset of the last generalized seizure in intact rats corresponded to 92 min with respect to the time of Na-PCN application. In rats with a lesion of the sensory cortex the last seizure was generated 433 min and in animals with a lesion of the motor cortex 167 min after Na-PCN treatment of the motor cortex of one side. This increase of latency of the last seizure was significant for the rats with a lesioned sensory area (p less than 0.02) or motor area (p = 0.05) compared to that of the intact rats. Additionally, the number of generalized seizures was significantly (p less than 0.01) increased by both groups of rats with a lesion of the motor or sensory cortex. 6. It is suggested that a substantial lesion of the cortex decreases predominantly the intrinsic cortical inhibition thus destabilizing brain function. This destabilizing effect becomes pronounced under the condition of superimposed suppression of the GABAergic cortical component. It is concluded that the intrinsic cortical inhibitory mechanism which in the intact brain acts against hyperexcitation and prevents the development of neuronal synchronization, i.e. the formation of seizures, becomes less effective in performing this task once an abnormal brain activation has developed.     

Behavioral consequences of isolation in early ontogeny in rats: selectivity of anxiety conditions

Multiparameter scale for evaluation of anxiety-phobic state in rats reveals significant enhancement of anxiety in rat pups after 6-week isolation (beginning from the 21st day from birth) as compared to grouped controls of the same litter: the locomotion and exploration that appear in test areas are suppressed, and species-specific fear reactions are enhanced. These changes considered as signs of situational anxiety are not eliminated by 2.5-month keeping in groups. Nevertheless, they are not correlated with parameters of the acoustic startle reflex that (by the data of literature) is thought to be related with fear and anxiety. On the basis of the discrepancy it is proposed that state of anxiety is selective. This suggestion is confirmed by individual behavioral variations characterized by a combination of a low level of situational anxiety and a high level of acoustic anxiety observed in both experimental and control groups. These variations may explain the existence of atypical "emotional resonance"-like behavior according to P.V. Simonov. Attention is given to selectively enhanced acoustic startle reflex in the group of active control as an evidence for critical importance of any manipulations with social context in early ontogeny.     

Reorganization of the Intact Somatosensory Cortex Immediately after Spinal Cord Injury

Sensory deafferentation produces extensive reorganization of the corresponding deafferented cortex. Little is known, however, about the role of the adjacent intact cortex in this reorganization. Here we show that a complete thoracic transection of the spinal cord immediately increases the responses of the intact forepaw cortex to forepaw stimuli (above the level of the lesion) in anesthetized rats. These increased forepaw responses were independent of the global changes in cortical state induced by the spinal cord transection described in our previous work (Aguilar et al., J Neurosci 2010), as the responses increased both when the cortex was in a silent state (down-state) or in an active state (up-state). The increased responses in the intact forepaw cortex correlated with increased responses in the deafferented hindpaw cortex, suggesting that they could represent different points of view of the same immediate state-independent functional reorganization of the primary somatosensory cortex after spinal cord injury. Collectively, the results of the present study and of our previous study suggest that both state-dependent and state-independent mechanisms can jointly contribute to cortical reorganization immediately after spinal cord injury.     

Natural head-forelimb coordination in dogs after vestibular de-afferentation

We studied the influence of the vestibular lesion on the natural head--forelimb coordination. This coordination exists in intact dogs at the early stage of acquisition of the instrumental feeding reaction of tonic forelimb flexion in order to hold a cup with meat during eating when the head is bent down to foodwell. In untrained dogs, the forelimb flexion is preceded by lifting the head bent down to the food; the following lowering of the head leads to extension of the flexed forelimb. For performing the instrumental reaction, the innate coordination has to be rearranged into the opposite one. It is achieved only by learning. After the lesion of the primary motor cortex contralateral to the "working" forelimb in trained dogs, the innate coordination reappears, whereas the learned coordination breaks down steadily. It was shown that bilateral vestibular lesion do not disturb the innate coordination in intact dogs at the early stage of learning and in trained dogs after the motor cortex lesion. It was concluded that the studied natural head--forelimb coordination is not connected with the vestibular reflex.     

Proteolytic processes in lung tissue of rat posterity after whole-body chronic irradiation with low doses

Intensification of proteolytic processes accompanied by inhibited antiprotease activity in lung tissue of first generation posterity of rats irradiated with a total dose of 0.25 Gy (0.01 Gy per day) before gestation was shown. The obtained data satisfied to imbalance in functioning of regulation systems, tension of adaptation mechanisms with possible rapider reduction of adaptation resistance of broncho-lung system of irradiated parents' posterity. Vector changes in correlation of indexes in the proteinase-antiproteinase system were analogous in all experimental series (irradiated male x irradiated female, irradiated male x intact female, intact male x irradiated female) with maximal expression in the group obtained from parents both irradiated before gestation. It could be possible to propose a presence of non-stable genome in posterity of irradiated parents, that satisfied to role of genetic aspects in development of the late functional disorders.     

Expression of N-methyl-D-aspartate (R)(GluN2B) - subunits in the brain structures of rats selected for low and high anxiety

In this paper, we studied differences in the density of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits in the brains of low (LR) and high (HR) anxiety rats subjected to extinction trials and re-learning of a conditioned fear response, modeling a natural course of anxiety disorders. Classifications of animals as LR or HR was determined by fear-induced freezing responses in the contextual fear test. Increased basal concentrations of GluN2B subunits were observed in the amygdala of HR rats as compared to the unconditioned control group by Western blot analysis. Re-exposure of HR animals to the fear-conditioned context resulted in elevated concentrations of GluN2B subunits in the amygdala, hippocampus and the prefrontal cortex compared to LR rats as well as in the hippocampus and prefrontal cortex vs. the control group. In addition, it was shown that re-test of a conditioned fear increased the number of cells expressing GluN2B subunits in the basolateral amygdala, dentate gyrus of the hippocampus and secondary motor cortex (M2) in the HR group relative to the LR group. Together, these data suggest that animals that are more anxious have altered patterns of GluN2B subunit expression in the frontal cortex and limbic structures, which control emotional behaviour.     

Dynamics of changes in somatosensory input to the motor cortex following lesion of somatosensory cortical areas in dogs

The pattern of change produced in somatosensory evoked potential (EP) in the forelimb projection area within the motor cortex (MI) following lesion of the projection area of the same limb in the somatosensory cortex (SI) or in parietal cortex area 5 was investigated during chronic experiments on waking dogs. Amplitude of the initial positive — negative wave of EP declined to 28–63% of preoperational level in all cases. No significant recovery of EP was noted for three weeks. Thus, a correlation between change in EP and spontaneous recuperation of the precision motor response occurring within two weeks after lesion of the SI did not exist. Nor was EP reinstated in the MI after ablation of area 5, despite complete but gradual reinstatement of EP (after an initial decline to 53%) in the nearby SI region. This protracted depression of EP seems to have been associated with breakdown of somatotopic sensory input from the SI or from area 5 to the MI, since EP in the motor cortex of the intact hemisphere and the hindlimb projection area within the MI on the lesioned side either remained unchanged or recovered within a week or two.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 61–68, January–February, 1990.     

Modulation of Sphingosine 1-Phosphate and Tyrosine Hydroxylase in the Stress-Induced Anxiety

Stress causes endocrinological changes and leads to induce anxiety. It was determined the anxiety and stress-related endocrinological changes through the observation of the level of glucocorticoid and sphingolipid metabolites in serum after stress. Immobilized stress and electric shock was applied to rats for 7 days. This study investigated the induction of anxiety, changes of TH and pERK expression in cortex and amygdala after stress. Also it was determined the changes of glucocorticoid and anxiety when the rats were given stress after amygdala lesion. The stress-given rats spent a lesser percentage of time significantly in the open arm than the control rats. The elevated level of glucocorticoid after stress was suppressed in amygdala lesion group. The expression of TH in the amygdala was decreased, but the expression of TH was not changed in the cortex after stress. To investigate the changes in sphingolipid metabolites after stress, the levels of sphingosine and the phosphate form of sphingolipid (So-1-P) were analyzed in serum. The level of So-1-P was elevated after stress and anxiety was observed after the So-1-P infusion (100 pmol/10 μl/h, i.c.v., for 7 days). Continuous infusion of So-1-P for 7 days led to the significant decrease of TH expression in the amygdala. In conclusion, the results of this study indicate that the lesion of amygdala suppressed the stress-induced anxiety and elevation of glucocorticoid in serum. It was also observed that expression of TH in amygdala as well as increased levels of glucocorticoid in serum might be responsible biomarker, at least in part, of chronic stress. These results suggest that the elevation of So-1-P might be involved in induction of anxiety during stress by the modulation of dopaminergic system in amygdala.     

Paradoxical facilitation of working memory after basolateral amygdala damage

Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect.     

Correlation of cutaneo-galvanic and voluntary reactions during recognition of emotional facial expressions

The frequency of skin-galvanic (SGR) and motor reactions was analyzed at recognition of human emotional state by mimics. 31 healthy persons and 54 patients with lesions of temporal and frontoparietal areas of both cerebral hemispheres were examined. It has been established that the process of recognition takes place by stages: at first - at intuitive level accompanied by SGR, and then at the level of making decision completed by a motor or verbal reaction. Efficiency of recognition at the first stage does not so much depend on lesion localization as at the second stage. Pathology of the left hemisphere affects mainly the stage of making decision, and of the right one - the process of recognition as a whole.     

On the Interrelationship of Speech Functioning and Manual Motor Activity in Aphasia

Clinicians, physiologists, and psychologists are familiar with cases of simultaneous disturbance of various functions in localized cerebral lesions. These phenomena have been studied and described repeatedly, but continue to be of substantial interest, as analysis of them may make a contribution to the study of localization of functions in the cerebral cortex, substitution and restoration of functions, and the nature of their interrelationships. Our attention was attracted by a case of simultaneous disturbance of motor function and the power of speech in a lesion of the left (dominant) hemisphere. We began by investigating motor functions in aphasia and in the normal state, with a view to subsequent comparison of the motor and verbal functions in the normal state and in aphasia.     

Functional properties of efferent zones of the motor cortex which project to ipsilateral and contralateral face muscles

In both intact (4 animals) and lesioned (2 preparations with contralateral motor cortex ablation and 1 animal with transection of the rostral two thirds of the corpus callosum) cats, three different types of efferent zones were identified in the face motor cortex by the technique of microstimulation: contralateral, ipsilateral and bilateral efferent zones. The three types of efferent zones had different organizational features such as location, thresholds of effective sites and latencies of motor responses. Mean thresholds of effective sites from ipsilateral and bilateral efferent zones in lesioned animals were not significantly higher than those in intact preparations. In both intact and lesioned animals, neurons endowed with contralateral, bilateral and ipsilateral receptive fields were isolated from the three types of efferent zones.     

Increased Neural Habituation in the Amygdala and Orbitofrontal Cortex in Social Anxiety Disorder Revealed by fMRI

A characterizing symptom of social anxiety disorder (SAD) is increased emotional reactivity towards potential social threat in combination with impaired emotion and stress regulation. While several neuroimaging studies have linked SAD with hyperreactivity in limbic brain regions when exposed to emotional faces, little is known about habituation in both the amygdala and neocortical regulation areas. 15 untreated SAD patients and 15 age- and gender-matched healthy controls underwent functional magnetic resonance imaging during repeated blocks of facial emotion () and object discrimination tasks (). Emotion processing networks were defined by a task-related contrast (). Linear regression was employed for assessing habituation effects in these regions. In both groups, the employed paradigm robustly activated the emotion processing and regulation network, including the amygdalae and orbitofrontal cortex (OFC). Statistically significant habituation effects were found in the amygdalae, OFC, and pulvinar thalamus of SAD patients. No such habituation was found in healthy controls. Concurrent habituation in the medial OFC and the amygdalae of SAD patients as shown in this study suggests intact functional integrity and successful short-term down-regulation of neural activation in brain areas responsible for emotion processing. Initial hyperactivation may be explained by an insufficient habituation to new stimuli during the first seconds of exposure. In addition, our results highlight the relevance of the orbitofrontal cortex in social anxiety disorders.     

The locked-in patient and the characteristics of the electrical activity of his brain

"Locked-in" state differs from the known states characterized by the motor activity blockade, preservation of conscience of speech contact, despite the fact that connection with outer world during this state is limited only by vertical movements of eyes and eyelids in response to speech signals. Three "locked-in" men were studied at different stages of development of this state. Spectral-coherent analysis of the EEG was conducted. The most typical for the developed state of the "locked-in" man is a uniform change of the intercentral EEG relations. In the motor areas of the cortex alpha-activity and its links are not formed (coherence in alpha-range is zero) while high and low frequencies are coherent. In the visual areas, in contrast, the alpha-rhythm is coherent. Distinct interhemispheric asymmetry of coherent connections appears. In the right hemisphere a decrease of coherence level is sharp and even, in the left one--in occipito-temporal parts the level remains close to norm, while in the frontal parts of the cortex it decreases.     

Impairement of estimation of the inner time and the emotional behavior in rats with the lesioned striatum and hippocampus

Bilateral lesion of the striatum delayed time conditioning in rats, induced anxiety, rearranged normal correlation between the anxiety level and autochronometrical ability. These shifts progressed along with an augmentation of the striatum lesion extent. Combined striat- and hippocampectomy as well as the latter alone resulted in a complete absence of time counting learning irrespective of the brain lesion extent. In these animals anxiety was also more obvious.     

Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice

Fruits of Fructus Schisandrae were used as sedatives and hypnotics in traditional Chinese medicine for a long history. In this study, we investigated the effects of schisandra lignans extract (SLE) on anxiety disorder in restraint-stressed mice using light-dark (L-D) test. The influences of restraint stress on the levels of monoamines: noradrenaline (NE), dopamine (DA) and serotonin (5-HT) in cerebral cortex, as well as plasma corticosterone (CORT) were studied in mice. The HPLC fingerprint of SLE was recorded and the percentage composition of Schisandra lignans was determined as 82.63%. In L-D test, it was found out that 18 h of restraint stress significantly decreased the anxiolytic parameters (explorative behaviors, e.g. number of entries, time spent) in light area indicating high state of anxiety in stressed mice. In addition, restraint stress elevated NE, DA, and 5-HT levels in cerebral cortex of anxiety mice. Plasma CORT level was also increased. Oral administration of SLE (100 and 200 mg/kg/day, 8 days) emolliating the level of stress-induced anxiety by significantly increasing the anxiolytic parameters mentioned above. We also observed decreases in cerebral cortex monoamines levels, as well as plasma CORT level in stressed mice. These results suggested that SLE reversed stress-induced anxiety level, changes of cortex monoamine transmitters and plasma CORT. The anxiolytic effects of SLE might be related to its anti-stress activity by modulation of hyperactive HPA axis.     

Plasticity of the behavior of Myrmica rubra ants during learning in a multi-alternative symmetric labyrinth

The ability was studied of Myrmica rubra ants to change the habit of passing through a multialternative symmetric labyrinth at motivation of the care for posterity. In exams the location of reinforcement was changed: in the first exam the progeny was carried from both aim places to those symmetric to them relatively to labyrinth cross axis; in the second exam the reinforcement was left on one aim place non-preferred during learning. The first exam was passed by 62.5% of ants, the second--by 87.5%. In the first exam such parameters were worse as the first correct decision, the mean number of movements in the cycle, the total number of correct cycles. At elaboration of new motor habits and increase and inversion were observed of the initial spatial-motor asymmetry. Individual variations in ants behaviour increased. The ants who failed to solve the task, showed pronounced signs of preneurotic state. The obtained results testify to a high plasticity of ants behaviour and their ability to modify their activity according to changes of experimental situation.     

化疗期乳腺癌患者情绪状态及其影响因素的调查研究

目的:调查化疗期乳腺癌患者的抑郁及焦虑情绪状态,探讨情绪状态的影响因素,促使医护人员更好的了解化疗期乳腺癌患者的情绪状态,以便更好的提供相应的护理与治疗。方法:采用自行设计的调查问卷,对2012年7~12月住院的97名化疗期乳腺癌患者进行调查,内容包括一般人口学资料、医院焦虑抑郁量表及状态-特质焦虑问卷。结果:化疗期乳腺癌患者的抑郁得分为(4.79±4.23)分,特质焦虑得分为(41.70±11.81)分,状态焦虑得分为(40.61±12.11)分,其影响因素包括教育水平和家庭人均月收入,Pearson相关分析得出特质焦虑、状态焦虑与抑郁之间存在正相关。结论:化疗期乳腺癌患者焦虑与抑郁处于较高水平,教育水平越高、家庭人均月收入越高的患者其焦虑、抑郁程度越低。医护人员可以通过对化疗期乳腺癌患者进行相应的心理疏导以减轻负性情绪的产生,以促进和保持治疗的顺利进行与疾病的转归。     

Exposure to neonatal separation stress alters exploratory behavior and corticotropin releasing factor expression in neurons in the amygdala and hippocampus

Evidence is accumulating that early emotional experience interferes with the development of the limbic system, which is involved in perception and regulation of emotional behaviors as well as in learning and memory formation. Limbic brain regions, as well as hypothalamic regions and other, nonlimbic areas contain specific neuron subpopulations, which express and release corticotropin releasing factor (CRF). Since these neurons serve to connect limbic function to endocrine, stress-related responses, we proposed that stressful experience during early postnatal brain development should interfere with the development of CRF-containing neurons, particularly in brain regions essential for emotional regulation. Applying neonatal separation stress (daily 1 h separation from the parents and litter mates) as stressor, the number of immunocytochemically identified CRF-expressing neurons/fibers was quantified in the amygdala, hippocampus, paraventricular nucleus of the hypothalamus, piriform cortex, and the somatosensory cortex of 3-week-old stressed and nonstressed Octodon degus, a semi-precocial rodent. Compared to controls neonatally stressed animals showed significantly lower levels of CRF-positive fibers (-60%) in the central amygdala, significantly less CRF-positive neurons in the dentate gyrus (-28%) and the CA1 region (-29%) and significantly lower CRF cell densities in the somatosensory cortex (-26%). On the other hand, we found significantly higher numbers of CRF-immunoreactive neurons in the basolateral amygdaloid complex (+192%) of stressed animals compared to nonstressed controls. No differences in CRF-immunoreactive cell densities were detected in the other regions. Additional behavioral analysis revealed significantly elevated exploratory behavior (+34%) in stressed animals compared to controls, which might indicate reduced anxiety in the stressed animals.