Maternal glucocorticoid hormones as a factor mediating the effect of prenatal stress on offspring anxiety

The plus-maze behavior was studied in offsprings of female rats subjected to immobilization stress on the 15-18 days of pregnancy. Prenatal stress decreased the level of anxiety in males and increased in females. The blockade of the mother's stress-induced glucocorticoid secretion by prior adrenalectomy and subsequent corticosterone injection during immobilization in a low dose (0.3 mg/kg) prevented the behavioral disorders in offsprings. In case of a higher dose of corticosterone (3 mg/kg) injection, the behavior of offsprings was the same as that of offsprings of the intact mothers subjected to immobilization. The results suggest that the stress-induced increase in maternal glucocorticoid level may be the mechanism by which prenatal stress impairs the development of sex differences in rat anxiety behavior.     

Somatic maturation and sensorimotor development of C57BL/6 mice prenatally exposed to cytosine arabinoside

The topical problem of experimental neurobiology is the development of pharmacological models to search for correlation between induced brain pathology and changes in behavioral phenotype. Cytosine arabinoside (Ara-c) is an antiproliferative agent, exposure to which in the critical period of the embryonic formation of the cortex results in the abnormality of its development. This study was aimed at estimation of the somatic and sensorimotor aspects of the early postnatal maturatrion of behavioral acts in mice with developmental abnormalities of the cortex induced by Ara-c. Pregnant C57BL/6 mice were injected with the substance on the 12.5th 13.5th gestation days. Offspring behavior was studied using a modified Fox battery on the 1st-21st postnatal days. Severe disorders of the sensorimotor development with slight somatic changes were revealed in the offsprings of Ara-c-treated mice. Features of these pathological changes point to a correlation between the developmental changes in behavioral phenotype and irregularities of the cortex formation. This experimental model can be applied to neurobiological and pharmacological studies.     

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5-C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.     

Further exploration into the adaptive design of the arthropod "microbrain": I. Sensory and memory-processing systems

Arthropods have small but sophisticated brains that have enabled them to adapt their behavior to a diverse range of environments. In this review, we first discuss some of general characteristics of the arthropod "microbrain" in comparison with the mammalian "megalobrain". Then we discuss about recent progress in the study of sensory and memory-processing systems of the arthropod "microbrain". Results of recent studies have shown that (1) insects have excellent capability for elemental and context-dependent forms of olfactory learning, (2) mushroom bodies, higher olfactory and associative centers of arthropods, have much more elaborated internal structures than previously thought, (3) many genes involved in the formation of basic brain structures are common among arthropods and vertebrates, suggesting that common ancestors of arthropods and vertebrates already had organized head ganglia, and (4) the basic organization of sensori-motor pathways of the insect brain has features common to that of the mammalian brain. These findings provide a starting point for the study of brain mechanisms of elaborated behaviors of arthropods, many of which remain unexplored.     

Significance of individual resistance to hypoxia for the correction of the brain trauma sequelae

In rats, the individual sensitivity to hypoxia plays an prominent role for recovery of animals after mechanic brain injury. Enthomerzol (25 mg/kg intraperitoneally) for three days after brain injury decreased behavioral disorders in rats with different resistance to acute hypoxia, recovered structure of individual behavior, prevented metabolic disorders in brain. Therefore, antihypoxant ethomerzol is effective as a drug against hypoxia due to brain injury.     

Activity of Zn-, Cu-containing superoxide dismutase in the brain tissue of rats with fetal alcohol syndrome

Zn(2+)-, Cu2+ superoxide dismutase activity was estimated in the brain of 14- and 30-day-old antenatally alcoholized rat offsprings. The enzyme activity in 14-day-old experimental offsprings. The enzyme activity in 14-day-old experimental offsprings was significantly decreased in the brain cortex, hippocampus and brain stem by 27.1; 31.1 and 33.4% respectively as compared with control animals. The results are discussed from the point of view of the activation of free radical processes in the brain of alcoholized offsprings.     

基于脑－肠轴理论探讨重症胰腺炎脑损伤“脑病治肠”的科学内涵

胰性脑病（pancreatic encephalopathy,PE）是重症胰腺炎患者病死的主要原因,目前尚无有效治疗手段。临床运用通腑泻下法进行“脑病治肠”的疗效确切,但其现代医学机制尚未完全阐明。肠道菌群与PE脑损伤的发生发展密切相关,且是脑－肠轴的核心通路,可通过迷走神经直接影响脑功能。通腑泻下代表方剂大承气汤可调节中枢神经系统炎症介质的释放,减轻PE脑损伤。以肠道菌群为切入点,从脑－肠轴调控机制的关键环节入手,全面分析肠道菌群构成、功能丰度及优势菌群,观察到胆碱能抗炎通路（cholinergic anti-inflammatory pathway,CAP）的活化程度影响中枢神经系统炎症因子的释放,最终改变PE脑损伤。本文阐述大承气汤通过肠道菌群调节CAP抗中枢神经系统炎症的分子机制,以期为中医以肠道菌群为靶点治疗PE提供理论依据,也为“脑病治肠”提供有力支持。

     

Lateralisation of the brain injury in female Wistar rats determines the immune and neurological status in offspring

The T-cell immune deficiency was found to be more obvious in offspring of rats with a right-side brain injury. The EMG pattern changed in accordance with the brain injury lateralisation in the muscles responsible for posture asymmetry. The offspring EMG disorders were more obvious in cases of a right-side brain injury in mothers. The right-side brain injury in mothers led to a higher negative emotionality and a diminished tentative-research behaviour in "open-field" tests in 30-day old offspring.     

Motor polarization dominance and "animal hypnosis"

Two kinds of dominanta were simultaneously formed under conditions of chronic experiments in rabbits. The motor polarization dominanta was formed under exposure of the right sensorimotor cortex of an animal to direct anodic current, and the state of "animal hypnosis" (the second dominanta) was induced. Animal behavior and electrophysiological characteristics were recorded. It was shown that the "animal hypnosis" induced at the optimum of the right motor polarization dominanta inhibited the motor reaction of the "dominant" extremity to testing stimuli. After the "animal hypnosis session, exposure of the right sensorimotor cortex to anodic current produced the latent excitation focus, which did not reach the level of summation. Two days later, exposure to testing stimuli developed the latent foci at first in the right cortex and then in subcortical structures. In the course of recovery of the motor polarization dominanta and its further change for the state characteristic of the "animal hypnosis", the patterns of cortical EEG coherence in the delta range typical of each kind of dominanta alternated in parallel with the time course of state changes.     

Ghrelin attenuates brain injury after traumatic brain injury and uncontrolled hemorrhagic shock in rats

Traumatic brain injury (TBI) and hemorrhagic shock often occur concomitantly due to multiple injuries. Gastrointestinal dysfunction occurs frequently in patients with TBI. However, whether alterations in the gastrointestinal system are involved in modulating neuronal damage and recovery after TBI is largely neglected. Ghrelin is a "gut-brain" hormone with multiple functions including antiinflammation and antiapoptosis. The purpose of this study was to determine whether ghrelin attenuates brain injury in a rat model of TBI and uncontrolled hemorrhage (UH). To study this, brain injury was induced by dropping a 450-g weight from 1.5 m onto a steel helmet attached to the skull of male adult rats. Immediately after TBI, a midline laparotomy was performed and both lumbar veins were isolated and severed at the junction with the vena cava. At 45 min after TBI/UH, ghrelin (4, 8 or 16 nmol/rat) or 1 mL normal saline (vehicle) was intravenously administered. Brain levels of TNF-α and IL-6, and cleaved PARP-1 levels in the cortex were measured at 4 h after TBI/UH. Beam balance test, forelimb placing test and hindlimb placing test were used to assess sensorimotor and reflex function. In additional groups of animals, ghrelin (16 nmol/rat) or vehicle was subcutaneously (s.c.) administered daily for 10 d after TBI/UH. The animals were monitored for 28 d to record body weight changes, neurological severity scale and survival. Our results showed that ghrelin downregulated brain levels of TNF-α and IL-6, reduced cortical levels of cleaved PARP-1, improved sensorimotor and reflex functions, and decreased mortality after TBI/UH. Thus, ghrelin has a great potential to be further developed as an effective resuscitation approach for the trauma victims with brain injury and severe blood loss.     

P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.     

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.     

Correlation of the rat behavior after immobilization with structural reorganization in the motor cortex

Behavioral changes and accompanying morphological neuron-glia reorganization in the rat brain were compared after emotional stress. Wistar rats (n = 20) were stressed by the interrupted immobilization, which was carried out during one week 7-8 h daily. Behavioral immobilization of rats was accompanied by an increase in horizontal and vertical locomotors activity and in duration of the III and IV phases of grooming ("comfortable" grooming) in the "open field" test. The morphometric studies showed a statistically significant increase in the density of hypoxic neurons in the right neocortex of the experimental animals as compared with control. Hypoxic changes in neurons were of functional character. Experimental rats can be considered as a model of redistribution of functional brain activity with preferential intensification of the left brain hemisphere.     

Substance P in the central mechanism of the rabbit feeding response evoked by stimulation of the lateral hypothalamus

The effects of substance P on the central mechanisms of food motivation elicited by electrical stimulation of the lateral hypothalamus were studied in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) brought about a dramatic reduction in the excitability of the "food center" in the hypothalamus, which returned to normal 45-60 minutes after injection. Higher concentrations of substance P provoked food behavior inversion up to the replacement of food motivation by avoidance behavior. Intravenous injections of substance P disturbed the relationships between the hippocamp, midbrain reticular formation and hypothalamus seen in health. This manifested in complete cessation of the inhibitory effects of the dorsal hippocamp and facilitating influences of the midbrain reticular formation on the excitability of the hypothalamic "food center". It is assumed that disorders of the central mechanisms of food motivation may arise from the effects produced by substance P directly on the central nervous system or on the brain via changes in the hormonal balance and responses of the autonomous nervous system.     

在大鼠创伤性脑损伤模型中神经干细胞移植对突触素表达的影响

目的探讨神经干细胞（NSCs）移植对创伤性脑损伤（TBI）模型大鼠感觉运动功能的恢复作用及其对损伤脑组织中突触素（SYP）表达的影响。方法体外培养大鼠胚胎皮质NSCs;采用Feeney法制备TBI模型,于造模后72h,移植组采用PKH26荧光示踪剂标记的NSCs直接移植于脑损伤区,对照组以等量生理盐水代替NSCs;分别于移植后不同时间点,采用Gridwalk和Latency试验检测TBI大鼠的感觉运动功能;荧光显微镜下计数移植细胞的存活数量;采用免疫印迹和RT-PCR技术检测脑损伤区及周围组织中SYP的表达。结果 NSCs移植大鼠前、后肢功能分别在移植后第2w和4w恢复至手术前水平,而直到第8w,对照组大鼠后肢功能和通过平板移动时间与NSCs移植组和基线比较仍有显著性差异（P〈0.05）。移植的NSCs随移植时间延长存活数量减少,移植后第4w和8w的存活数分别为6.3%±1.0%和4.1%±0.9%。在移植后的8w期间,移植组脑损伤区及周围组织中SYP的表达均明显高于对照组（P〈0.05）。结论移植的NSCs在TBI脑内能够存活,并明显改善了TBI大鼠对侧肢体的感觉运动功能;NSCs移植促进了脑损伤区及周围组织中SYP的表达,这可能是NSCs移植促进功能恢复的机理之一。     

Some mechanisms of adenosine protective effect in the "calcium paradox"

A possibility of preventing the "calcium paradox" with the aid of adenosine was studied as well as some mechanisms of adenosine effect upon the heart in case of the "calcium paradox". Adenosine was found to suppress release of amino acids from the heart in perfusion with calcium-free medium, to efficiently prevent disorders in the energy-dependent functions of mitochondrion and myoglobin release from the heart in reperfusion with Ca2+ -containing solution. Adenosine was also found to increase 2-10-fold lactate release from the heart. Adenosine seems to be able to activate glycolysis. Iodine acetate was shown to completely suppress the adenosine ability to decrease amino acid release from the heart perfused with calcium-free medium. Under conditions of iodine acetate blocking of glycolysis was found to possess no protective properties against cytolysis in the "calcium paradox". The heart mitochondria isolated in the end of the experiment revealed low values of free or phosphorylating respiration and complete dissociation of oxidation. Also a protective effect of adenosine in inhibition of Na+, K+ -ATPhase with Strophantinum, was studied.     

Sex differences in the influence of mothers on the sociosexual preferences of their offspring

The extent to which "nurture" as opposed to "nature" determines behavior and sociosexual preferences in mammalian species is controversial although most recent interest has focused on genetic determinants. We report here that if sheep and goats are cross-fostered at birth, but raised in mixed-species groups, their play and grooming behavior resembles that of their foster rather than genetic species. There are no sex differences in effects on these behaviors, and other species-specific behavior patterns such as aggression, browsing, climbing, and vocalizations are unaffected. In adulthood, cross-fostered males strongly prefer to socialize and mate with females of their foster mother's species, even if raised with a conspecific of their own species. Castration within 2 days of birth slightly reduces the level of this altered social preference but mating preference following short-term testosterone treatment is the same as for gonadally intact animals. Cross-fostered females also show significant preference for socializing with females and mating with males of their foster mother's species, although this effect is weaker than that in both gonadally intact and castrated males. When cross-fostered animals are placed in flocks containing members of only their genetic species for 3 years, male social and mating preferences for females of their mother's species remain virtually unaffected. Females change to display an exclusive mating preference for members of their genetic species in 1-2 years although they still retain some social interest in female members of their foster species. Thus, there are clear sex differences in the impact of the emotional bond between a mother and her offspring in these mammals. Effects on males are strongest and irreversibly maintained even after altering their social environment, whereas those on females are weaker and mating preferences are clearly adaptable in the face of altered social priorities. These sex differences are presumably caused by pre-, or early postnatal, organizational effects of sex hormones on the brain.     

A spectral-correlational analysis of the electrical activity of the sensorimotor cortex and the internal geniculate body during a motor-polarization dominant]

By spectral-correlative analysis the dynamics was studied of structural changes of coherent relations of the electrical activity of the sensorimotor cortex and medial geniculate body (MGB) of the rabbit under motor polarization dominant created by the action of DC anode on the sensorimotor cortex area. It was shown, that in the power spectra of the MGB, besides the increase of the delta-region components in interstimulus intervals at the dominant, during the action of the sound stimulus a distinct maximum appeared in the alpha-rhythm range of the electrical activity of MGB of the "dominant" hemisphere. The coherence increase of the delta-range of the MGB and the sensorimotor cortex electrical activity in the "dominant" part of the brain was manifested exclusively in the period of sound stimulus action.     

The efficacy of mesenchymal stem cells for the improvement of cerebral microcirculation in spontaneously hypertensive rats

Elaboration of new correction methods for microcirculatory disorders in the brain caused by persistent high blood pressure is important for both medicine and biology. We studied the influence of intracerebral transplantation of human mesenchymal stem cells (hMSCs) on the cerebral microcirculation in young (4 month) and mature (12 month) spontaneously hypertensive rats (SHRs). It was shown that hMSC transplantation increased the density of the microvascular network of young SHRs to 1.6 and 1.9 times the density of the arteriolar area of the microvascular network of the pia. The density of microvascular network of mature SHRs increased by 1.4–1.5 times after hMSC transplantation. The perfusion and tissue saturation of sensorimotor cortex of young SHRs restored to the level of young normotensive rats. In mature SHRs, the perfusion and tissue saturation of sensorimotor cortex did not increase. In conclusion, the intracerebral transplantation of hMSC almost completely restored microcirculation in the sensorimotor cortex of the brain of young SHRs and slightly improved microcirculation in mature SHRs.     

Activin in the brain modulates anxiety-related behavior and adult neurogenesis

Activin, a member of the transforming growth factor-beta superfamily, is an endocrine hormone that regulates differentiation and proliferation of a wide variety of cells. In the brain, activin protects neurons from ischemic damage. In this study, we demonstrate that activin modulates anxiety-related behavior by analyzing ACM4 and FSM transgenic mice in which activin and follistatin (which antagonizes the activin signal), respectively, were overexpressed in a forebrain-specific manner under the control of the alphaCaMKII promoter. Behavioral analyses revealed that FSM mice exhibited enhanced anxiety compared to wild-type littermates, while ACM4 mice showed reduced anxiety. Importantly, survival of newly formed neurons in the subgranular zone of adult hippocampus was significantly decreased in FSM mice, which was partially rescued in ACM4/FSM double transgenic mice. Our findings demonstrate that the level of activin in the adult brain bi-directionally influences anxiety-related behavior. These results further suggest that decreases in postnatal neurogenesis caused by activin inhibition affect an anxiety-related behavior in adulthood. Activin and its signaling pathway may represent novel therapeutic targets for anxiety disorder as well as ischemic brain injury.