Viruses Challenge Selectivity Barrier of Nuclear Pores

Exchange between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC permeability barrier restricts the entry of inert molecules larger than 5 nm in diameter but allows facilitated entry of selected cargos, whose size can reach up to 39 nm. The translocation of large molecules is facilitated by nuclear transport receptors (NTRs) that have affinity to proteins of NPC permeability barrier. Viruses that enter the nucleus replicate evolved strategies to overcome this barrier. In this review, we will discuss the functional principles of NPC barrier and nuclear transport machinery, as well as the various strategies viruses use to cross the selective barrier of NPCs.     

Corticofugal direct projections to primary afferent neurons in the trigeminal mesencephalic nucleus of rats

Little is known about projections from the cerebral cortex to the trigeminal mesencephalic nucleus (Vmes) which contains the cell bodies of primary sensory afferents innervating masticatory muscle spindles and periodontal ligaments of the teeth. To address this issue, we employed retrograde (Fluorogold, FG) and anterograde (biotinylated dextranamine, BDA) tracing techniques in the rat. After injections of FG into the Vmes, a large number of neurons were retrogradely labeled in the prefrontal cortex including the medial agranular cortex, anterior cingulate cortex, prelimbic cortex, infralimbic cortex, deep peduncular cortex and insular cortex; the labeling was bilateral, but with an ipsilateral predominance to the injection site. Almost no FG-labeled neurons were found in the somatic sensorimotor cortex. After BDA injections into the prefrontal cortex, anterogradely labeled axon fibers and boutons were distributed bilaterally in a topographic pattern within the Vmes, but with an ipsilateral predominance to the injection site. The rostral Vmes received more preferential projections from the medial agranular cortex, while the deep peduncular cortex and insular cortex projected more preferentially to the caudal Vmes. Several BDA-labeled axonal boutons made close associations (possible synaptic contacts) with the cell bodies of Vmes neurons. The present results have revealed the direct projections from the prefrontal cortex to the primary sensory neurons in the Vmes and their unique features, suggesting that deep sensory inputs conveyed by the Vmes neurons from masticatory muscle spindles and periodontal ligaments are regulated with specific biological significance in terms of the descending control by the cerebral cortex.     

Effect of Deep Brain Stimulation of the ventromedial prefrontal cortex on the noradrenergic system in rats

Background

Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC) is a promising therapeutic alternative to treat resistant major depressive disorder. In preclinical studies, DBS of the ventromedial prefrontal cortex (vmPFC, the rodent SCC correlate) provokes an antidepressant-like effect, along with changes in noradrenaline levels at the site of stimulation. Hence, DBS appears to activate the noradrenergic-locus coeruleus (LC) system.

The FG syndrome: 7 new cases

The X-linked FG syndrome is characterised by mental retardation, congenital hypotonia and constipation (which may both be severe), structural anal anomalies and relative macrocephaly in some, and an unusual and characteristic facial appearance. We describe 7 males from 4 families. One had anal stenosis. Two of the mothers and one sister show probable carrier manifestations. The features of the FG syndrome are individually non-specific. We emphasize that the characteristic combination of features is needed to avoid overdiagnosis.     

Ethopharmacological analysis of the unstable elevated exposed plus maze,a novel model of extreme anxiety: predictive validity and sensitivity to anxiogenic agents

RATIONALE AND OBJECTIVES: The unstable elevated exposed plus maze (UEEPM) has been proposed as a novel model of anxiety which elicits unconditioned escape-related behaviour in rats thought to mimic the persistent "fight/flight" state exhibited by patients suffering from extreme anxiety disorders. This study investigated the predictive validity of the UEEPM by examining the behaviour of rats exposed to the test following administration of drugs known to induce panic and anxiety in panic disorder and post-traumatic stress disorder patients, namely m-chlorophenylpiperazine (mCPP), caffeine and yohimbine. The sensitivity of the UEEPM to two further putative anxiogenic agents, the benzodiazepine partial inverse agonist FG 7142 and pentylenetetrazole (PTZ), was also assessed. METHODS: Male Hooded Lister rats received a single dose of mCPP (0.5-2.0 mg/kg; ip), caffeine (3.0-30.0 mg/kg; ip), yohimbine (1.25-5.0 mg/kg; ip), FG 7142 (3.0-30.0 mg/kg; ip) or PTZ (3.0-30.0 mg/kg; ip) before being exposed to the UEEPM for a period of 5 min. Subjects' behaviour was analysed to determine the effects of each compound on unconditioned escape. RESULTS: mCPP (1.0 and 2.0 mg/kg), caffeine (30 mg/kg), FG 7142 (3.0 and 30.0 mg/kg) and PTZ (30.0 mg/kg) significantly increased animals' propensity to escape from the UEEPM, i.e. they had a clear anxiogenic effect, whilst yohimbine had no effect on escape. CONCLUSIONS: The UEEPM is sensitive to the behavioural effects of anxiogenic agents. Furthermore, pharmacological similarities exist between symptoms of panic and anxiety in patients and escape from the UEEPM in rats. The UEEPM may therefore represent a paradigm to facilitate investigation into the neurochemical basis of extreme anxiety disorders.     

Neonatal development of projections to the basolateral amygdala from prefrontal and thalamic structures in rat

Recently an animal model for neurodevelopmental disorders has been developed. In this model the effects of an early neonatal [postnatal day 7 (Pd7)] basolateral amygdala lesion are compared with the effects of a lesion later in life (Pd21). Early amygdala damage results in enduring behavioral disturbances that become more manifest after puberty. These disturbances were not present in animals lesioned at Pd21. Accordingly it was postulated that the early damage may affect the neuroanatomical and neurochemical organization and functioning of other brain structures. To obtain information on the innervation of the amygdala during normal development, we used the retrograde tracer fluoro-gold. From neonatal day 7 onward (studied until Pd19), retrogradely labeled cells were present in the caudal and rostral thalamus, the substantia innominata, and the prefrontal but not the caudal cortex. Development of the topography of the projecting cells differed substantially for the thalamic regions and substantia innominata vs. the cortical regions. In thalamic regions and substantia innominata, no changes were observed during the studied period (Pd7-Pd9). In the prefrontal cortex, the number of labeled cells increased (from Pd7 to Pd13), the topography of the location of the cells changed from unilateral to bilaminar (from Pd9 to Pd13), and the number of subareas in which the cells were present increased (from Pd7 to Pd13). In the caudal cortex, relatively few cells were present up to Pd15. From Pd17 onward, a bilaminar topography of the location of the cells was observed. These data provide information on the circuitry that may be involved in the aberrant neurodevelopment of neonatally amygdala-lesioned rats, which has been proposed as an animal model for neurodevelopmental psychopathological disorders.     

大鼠脊髓向延髓网状背侧亚核投射神经元的形态及分布

既往的电生理学研究已经证实,位于延髓尾侧部的网状背侧亚核（subnucleusretlcularlsdorsalls．SRD）对伤害性信息的调控具有重要作用j',SRD神经元可被来自全身各部的AS或C纤维的冲动所兴奋,这种兴奋可被吗啡抑制,又可被纳洛酮所翻转"。。形态学研究也表明,在脊髓和S...     

Effects of 8-OH-DPAT,buspirone and ICS 205-930 on feeding in a novel environment: comparisons with chlordiazepoxide and FG 7142

Previously, the 5-hydroxytryptamine (5-HT)_1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone and the 5-HT₃ receptor antagonist ICS 205-930 have been shown to exert anxiolytic-like effects in several animal models. In the experiments reported here the effects of these compounds on feeding behaviour and food preference in a novel environment were examined, and compared with the effects of the anxiolytic drug chlordiazepoxide and the anxiogenic compound FG 7142. Chlordiazepoxide significantly reduced the latency to begin eating and prolonged the total time spent eating; chlordiazepoxide also abolished food neophobia, by significantly increasing the time spent eating novel food items. In contrast, FG 7142 significantly increased eating latency and reduced eating duration. Both 8-OH-DPAT and buspirone significantly enhanced eating duration, but unlike chlordiazepoxide eating was directed only towards the familiar food. In addition buspirone, but not 8-OH-DPAT, reduced eating latency. ICS 205-930 significantly increased eating latency and reduced eating duration; however, these effects were observed only at the lowest dose tested. All of these behavioural effects were observed only when animals were unfamiliar with the testing situation, and cannot be accounted for in terms of changes in mechanisms controlling hunger. The behavioural paradigm used in these experiments may induce a competition between the drives to explore a novel environment and to eat. It is suggested that the tendency of buspirone and 8-OH-DPAT to suppress exploratory activity may thus result in enhanced feeding duration. Similarly enhanced exploratory activity induced by ICS 205-930 may result in animals taking longer to contact food, and spending less time eating. These results serve to illustrate that compounds which have different pharmacological actions, but which have been shown in other tests to have anxiolytic-like activity, can induce different behavioural effects. The suitability of this behavioural test for assessing anxiolytic effects of drugs is discussed.     

当归对~(60)Co-γ射线照射后家兔染色体作用的研究

本文采用当归对辐射损伤的家兔进行腹腔注射,引起家兔染色体畸变率明显下降,连续注射9天,家兔染色体畸变率完全恢复正常。体外用药实验结果与体内注射结果相同。