Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure.

OBJECTIVE: To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. METHODS: One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. RESULTS: The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB. CONCLUSION: Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

Proteasome inhibition induces DNA damage and reorganizes nuclear architecture and protein synthesis machinery in sensory ganglion neurons.

Bortezomib is a reversible proteasome inhibitor used as an anticancer drug. However, its clinical use is limited since it causes peripheral neurotoxicity. We have used Sprague-Dawley rats as an animal model to investigate the cellular mechanisms affected by both short-term and chronic bortezomib treatments in sensory ganglia neurons. Proteasome inhibition induces dose-dependent alterations in the architecture, positioning, shape and polarity of the neuronal nucleus. It also produces DNA damage without affecting neuronal survival, and severe disruption of the protein synthesis machinery at the central cytoplasm accompanied by decreased expression of the brain-derived neurotrophic factor. As a compensatory or adaptive survival response against proteotoxic stress caused by bortezomib treatment, sensory neurons preserve basal levels of transcriptional activity, up-regulate the expression of proteasome subunit genes, and generate a new cytoplasmic perinuclear domain for protein synthesis. We propose that proteasome activity is crucial for controlling nuclear architecture, DNA repair and the organization of the protein synthesis machinery in sensory neurons. These neurons are primary targets of bortezomib neurotoxicity, for which reason their dysfunction may contribute to the pathogenesis of the bortezomib-induced peripheral neuropathy in treated patients.

The cytoarchitecture of the adult human parabrachial nucleus: a Nissl and Golgi study.

The parabrachial nucleus (PBN) plays important roles in numerous autonomic functions and in pain modulation. In different animal species, three main regions of the PBN have been identified: the m-PB, the l-PB, and the Kolliker-Fuse nucleus (KF). The KF has not been identified in humans. The present study used Nissl and Golgi-Cox material and morphoquantitative methods to investigate the cytoarchitectural organization of the adult human PBN, paying particular attention to neuronal features endowed with functional significance, i. e. the arborization of the neurons. The PBN neuron population is made up of elements which are heterogeneous in size, shape and dendritic arborization, and grouped into two regions, the lateral and medial PBN (l- and m-PB). It has been suggested that some large sized neurons located in the ventral region of the m-PB might be the counterpart of the KF. In the m-PB the fusiform neurons are the most numerous cells; in the l-PB the multipolar neurons prevail, and are particularly numerous in the dorsal l-PB. Since the dendritic arborization is generally the main target of afferent projections to a neuron, it is possible that the l-PB, and in particular its dorsal region, might be the main site for the endings of afferences to the human PBN.

Local cerebral blood flow during the first hour following acute ligation of multiple arterioles in rat whisker barrel cortex.

The objectives are to measure the early time-course of the flows of blood, red cells, and plasma in brain tissue destined to infarct following arterial occlusion. The flux of fluorescent red blood cells (fRBCs) through venules and the arteriovenous transit times (AVTT) of fluorescein-labeled plasma albumin were periodically monitored in anesthetized adult Wistar rats before and up to 60 min after permanent ligations of several small branches of the middle cerebral artery. Of note, fRBC is a function of venular erythrocyte flow and volume, whereas AVTT is a function of plasma flow and volume in visible arteriole-capillary-venule units. In another group of anesthetized rats, local cerebral blood flow (ICBF) was measured 1 h after permanent arterial occlusion by [14C]iodoantipyrine (IAP) autoradiography. With this model of focal ischemia, the lesion is highly reproducible and involves part of the whisker barrel cortex. Infarction of this area was observed in 12 of 13 rats. From 10 to 60 min after arterial occlusion, AVTT was nearly four times longer in the ischemic barrel cortex than at the same site before ligations, and fRBC flux was 25%. Neither parameter changed appreciably over this time. After 60 min of ischemia, ICBF on the ipsilateral barrel cortex was 18% of that on the contralateral side and 15% of the sham control value for the same area of the barrel cortex. Since whole blood flow in the ischemic barrel cortex was < 20% of normal at 60 min and AVTT and fRBC flux were essentially constant from 10 to 60 min, the rates of plasma and red cell flows were similarly depressed during the first hour of arteriolar occlusion. In conclusion, such lowering of red cell, plasma, and blood flows produced consistent infarctions in the barrel cortex.

The use of texture analysis to study the time course of chromatolysis.

Image analysis of the textural feature entropy of the Nissl substance was used to monitor the time course of chromatolysis in regenerating hypoglossal motoneurons and degenerating facial motoneurons 4-112 days after hypoglossal-facial anastomosis in rats. Changes in the Nissl substance were detected that were not obvious on the basis of subjective judgement of the light-microscopical appearance of the neurons. Chromatolysis started 4 days post operation (dpo) and was not reversed at 112 dpo in both nuclei. The increase of chromatolysis was 14-28 dpo faster in the regenerating hypoglossal neurons than in degenerating facial neurons. Maximal chromatolysis was measured at 56-70 dpo in both nuclei. Afterwards chromatolysis persisted at a significantly higher level in the degenerating facial motoneuron pool. In conclusion, chromatolysis is a very long persisting reaction. In the beginning chromatolysis is faster and greater in regenerating rather than in degenerating neurons. In contrast, passing the maximal reaction, chromatolysis is maintained at a higher level in degenerating motoneurons. Image analysis of textural features is a suitable and reliable tool to monitor the time course of neuronal cell body changes. The presented quantitative method could be applied in any neurobiological study influencing the regeneration or degeneration of motoneurons.

Quantitative image analysis of the chromatolysis in rat facial and hypoglossal motoneurons following axotomy with and without reinnervation.

Image analysis was used to quantify the time course of chromatolysis in regenerating and degenerating motoneurons. Following facial-facial, hypoglossal-hypoglossal nerve suture, or resection of facial and hypoglossal nerves with postoperative survival times of 4 h to 112 days, the texture of the Nissl substance of facial and hypoglossal motoneurons was analyzed on both sides of the brainstem in paraffin serial sections with a VIDASplus image analyzer. In this quantitative study of 149 Wistar rats, alterations of the Nissl substance were measured that were statistically significant but not yet visible to the human eye. Chromatolysis started significantly as early as 8 h and was not fully reversed 112 days after any of the types of axotomy. The reaction was more intense and longer lasting following axotomy without reinnervation than with reinnervation. Thus, chromatolysis starts much faster and lasts far longer than was previously known. The quantified chromatolysis is much stronger after permanent target deprivation than during complete regeneration of motoneurons but is reversible in both cases.

[DNAse-I inhibition by the chromatin proteins of the brain cells in rats]. / Ingibirovanie DNKazy-I belkami khromatina kletok golovnogo mozga krys.

The effect of protein extracted from nuclei of brain cells on the reaction of DNA-ethidium bromide complex interaction with DNAase I and Bac. subtilis nuclease was studied. The nuclei were isolated from the brain of Wistar male rats weighting 180-200 g. The fluorescence was recorded on a Hitachi MPF-44B spectrofluorimeter. Proteins extracted from the nuclei with 0.6 NaCl substantially inhibited the DNAase I but not Bac. subtilis nuclease activity. Other studied fractions of nuclei lacked the capacity for inhibiting DNAase I.

Kainic acid lesions of the superior olivary complex: a horseradish peroxidase study of surviving brain-stem projections.

Lesions of the superior olivary complex of the adult ferret were made by pressure injection of kainic acid (5 nM/microliters in Locke's solution) through a glass micropipette inserted into the lower brain-stem. Small injections of kainic acid (1.5 microliters) produced a localized loss of nerve cells in the superior olivary complex in the vicinity of the pipette tip without apparent damage to fibers of passage in the trapezoid body. The extent of neural damage was determined by the absence of cell bodies in Nissl-stained sections. Integrity of fibers in the trapezoid body and other decussating pathways of the auditory lower brain-stem was confirmed by retrograde transport of horseradish peroxidase (HRP) following large injections of the enzyme into the central nucleus of the inferior colliculus. Even animals with complete destruction of the superior olivary complex had a normal complement of HRP-labelled cells in all divisions of the cochlear nucleus (the dorsal, anteroventral and posteroventral nuclei) contralateral to the HRP injection. In cases with partial lesions, normal labelling was also seen in those parts of the superior olivary complex not directly destroyed by the kainic acid injection. There was no evidence of disruption of fibers of passage nor was there any indication of abnormal projections from the lower brain-stem to inferior colliculus even after prolonged survival times.

[The selective participation of brain-specific non-histone proteins of chromatin Np-3,5 during the reproduction of a defensive habit to food in edible snails]. / Izbiratel'noe uchastie mozgospetsificheskikh negistonovykh belkov khromatina Np-3,5 v protsessakh vosproizvedeniia oboronitel'nogo navyka na pishchu u vinogradnykh ulitok.

The role of brain-specific nonhistone proteins of chromatine Np-3.5 in the processes of reproduction of elaborated defensive habit to food was studied in previously learning snails. It was found, that gamma-globulines to Np-3.5 during tens of minutes inhibited behavioural and neuronal reactions elicited by a definite conditioned stimulus--carrot juice, without changing reactions to other conditioned stimulus--apple juice. gamma-globulines to other nonhistone proteins of chromatine did not influence the reproduction of food rejection habits. It was supposed that brain-specific nonhistone proteins of chromatine Np-3.5 were selectively involved in the molecular processes providing for neurophysiological mechanisms of information extraction from the long-term memory.

[The structure and transcription activity of the neuronal chromatin in the sensorimotor cortex during postnatal differentiation]. / Issledovanie struktury i transkriptsionnoi aktivnosti khromatina neironov sensomotornoi kory v period postnatal'noi differentsirovki.

We report findings about age-related changes in the chromatin structure detected using ammoniacal silver and changes in the transcription rate in neurons by layers II-V of the sensomotor cortex of rats at days 7, 14 and 60 of postnatal life. Different types of neurons showed different average template activity but similar patterns of its age-related changes. The rearrangement of the chromatin structure in various types of cortical cells showed different orientation after day 14 of postnatal life.

[Cosinor analysis of the circadian dynamics of transcription in populations of neurocytes from a number of sections of the rat nervous system]. / Kosinor-analiz tsirkadnoi dinamiki transkriptsii v populiatsiiakh nevrotsitov riada otdelov nervnoi sistemy krys.

Diurnal fluctuations of endogenous RNA polymerases activity were studied in the cell nucleus of the cerebral stem and spinal nervous system populations (neurocytes of the hypothalamic suprachiasmatic nuclei, superior cervical ganglia, spinal ganglia L5, motoneurones of the spinal cord and Purkinje cells) were revealed. The acrophases of the visual cortex neurones were observed just before light reception.

[Peripheral neuropathies. Current data concerning nerve regeneration (author's transl)]. / Neuropathies périphériques. Connaissances concernant la régénération nerveuse.

The peripheral neuropathies in humans could be classified both with clinical criteria and pathological aspects. Between these, only axonal neuropathies are subject to regeneration. Axonal neuropathies present two aspects: wallerian degeneration and dying-back neuropathy. Dying-back neuropathy is the commonest type of human neuropathy but wallerian degeneration has been the most studied model of axonal neuropathy. The regeneration in this case lead to two questions: what is the signal for regeneration and what are the factors which improve the nerve growth?

[Relationship between the spike responses of crayfish mechanoreceptor neurons and the initial functional state and degree of aggregation of their Nissl substance]. / Zavisimost' impul'snykh reaktsii mekhanoretseptornogo neirona rechnogo raka ot iskhodnogo funktsional'nogo sostoianiia i stepeni agregatsii veshchestva Nisslia.

The discharges of a single neuron in the crayfish isolated stretch receptor to square standard adequate stimuli were studied. The following parameters were analyzed: response duration, number of impulses per burst, inhibitory pause duration, amplitude and shape of the frequencygram. Preliminary desaggregation of Nissl substance correlated with increase in discharges. When initial frequency of the discharge was low or when the stretch receptor was in resting state, especially in winter time, and the Nissl substance showed high degree of aggregation, discharges to the same stimuli were weaker, and their range diminished. It is suggested that intensified discharges are determined by intracellular redistribution and uptake of calcium which take place during desaggregation of the Nissl substance.