Hypothalamo-pituitary neurosecretory system of the Northern redbacked vole Clethrionomys rutilus in the course of population cycle

Hypothalamo-pituitary neurosecretory system (HPNS) of the Northern redbacked vole, Clethrionomys rutilus was studied at different stages of the population cycle using paraldehyde-fuchsin staining and immunohistochemical revealing of vasopressin and oxytocin. We found at the stages of high voles number (peak and recession), an increase of vasopressin synthesis in the neurosecretory cells (NSC) of paraventricular (PVN) and supraoptic (SON) nuclei, as well as its active transport and release to the portal capillaries of the outer zone of median eminence (ME). At the stages of low voles number (depression and growth) was demonstrated that level of oxytocin synthesis in the NSC of SON was high and moderate in the NSC of PVN, which was accompanied by an extensive release of oxytocin to capillaries of the posterior pituitary (PP). Increased supply of vasopressin to portal blood flow of the vole pituitary in conditions of overpopulation is suggested to have highly stimulating influence on adrenocorticotropic function of pituitary, which negatively affects the reproductive function of the voles and leads to a decrease of their number. At the stages of low number of population in conditions favoring the life of the voles, the increased supply of oxytocin to the systemic blood flow stimulates the reproductive behavior of the voles, which results in rise of their population during this period.     

Participation of catecholamines and NO in regulation of apoptosis of nonapeptidergic neurons of neonatal rat pups

Effects of catecholamines (CA) and the character of interaction of CA and NO in regulation of apoptosis were studied in vasopressinergic (VP-ergic) neurons of supraoptic (SON) and paraventricular (PVN) nuclei of rat pups in early postnatal ontogenesis. To study role of CA in regulation of programmed cell death in SON and PVN in the course of embryonal development, pregnant female rats were intraperitoneally injected daily from the 13th to the 20th day with αMPT—a blocker of CA synthesis. The second group of pregnant rats was injected from the 13th to the 20th day with the same volume of saline. The third group was composed of intact animals. The born rat pups were sacrificed at the 3rd and 15th days of life. Caspase 9, Bcl-2, tyrosine hydroxylase, and neuronal NO-synthase (nNOS) in SON and PVN neurons were revealed immunohistochemically, and the amount of immunoreactive substance in neuronal bodies was estimated using the computerized digital analyzer of TV image and Video Test software. Caspase-9 was shown to play an important role in postnatal formation of cellular composition of hypothalamic nonapeptidergic centers by leading to initiation of apoptosis and rejection of “useless” postmitotic SON and PVN neurons. Survival of “useless” nonapeptidergic neurons in early postnatal ontogenesis seems to be connected with antiapoptotic action of Bcl-2. Death of postmitotic neurons, and therefore formation of cellular composition begins earlier and, accordingly, is completed earlier in SON, in which neurons were noted to have a considerable decrease of the caspase-9 expression and, therefore, also a decrease of intensity of neuronal death via caspase-9-dependent pathway. In PVN, neurons continue to die also at the 15th day of rat life, i.e., almost two weeks later than in SON. The observed high correlation between the content of nNOS, caspase-9, and Bcl-2 in the SON and PVN neurons of intact rats of both age groups allows suggesting participation of NO in realization of apoptosis in the course of early postnatal development. The increase of nNOS expression in hypothalamic neurons as a result of disturbances in CA-ergic innervation in embryogenesis might be a possible cause of the long preserved enhancement of expression of apoptosis signal proteins. It can be suggested that CA participate in morphogenesis of hypothalamic neurons by increasing expression of nNOS in neurons and thereby affecting expression of apoptotic proteins.     

<Emphasis Type="Italic">Homo loquens</Emphasis>: Evolution of cerebral functions and language

The paper reviews the state of the problem of evolution of language and brain. Various points of view are considered: nativism and connectionism, principle of modular organization of the higher psychic functions including language, and that of organization of all functions on the basis of the network and associative principle. There is also considered the justifiability of the idea of macromutation that has resulted in the appearance of language and a series of micromutations that have led to the same. Also considered are specific verbal disturbances including genetic ones.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 400–406.Original Russian Text Copyright © 2004 by Chernigovskaya.To the 100-Anniversary of N. N. Traugott     

Inhibition of ERK1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures

It has recently been proposed that extracellular signal‐regulated kinases 1 and 2 (ERK1/2) are one of the factors mediating seizure development. We hypothesized that inhibition of ERK1/2 activity could prevent audiogenic seizures by altering GABA and glutamate release mechanisms. Krushinsky–Molodkina rats, genetically prone to audiogenic seizure, were recruited in the experiments. Animals were i.p. injected with an inhibitor of ERK1/2 SL 327 at different doses 60 min before audio stimulation. We demonstrated for the first time that inhibition of ERK1/2 activity by SL 327 injections prevented seizure behavior and this effect was dose‐dependent and correlated with ERK1/2 activity. The obtained data also demonstrated unchanged levels of GABA production, and an increase in the level of vesicular glutamate transporter 2. The study of exocytosis protein expression showed that SL 327 treatment leads to downregulation of vesicle‐associated membrane protein 2 and synapsin I, and accumulation of synaptosomal‐associated protein 25 (SNAP‐25). The obtained data indicate that the inhibition of ERK1/2 blocks seizure behavior presumably by altering the exocytosis machinery, and identifies ERK1/2 as a potential target for the development of new strategies for seizure treatment.

     

Effect of Block of Catecholamine Synthesis on the Functional State of Vasopressinergic Neurons of Hypothalamus in Dehydrated Rats

Effect of catecholamines (CA) on the functional state of vasopressin (VP)-ergic neurons of hypothalamus at their stimulation produced by dehydration (salt diet and water deprivation) was studied in in vivo experiments on adult male Wistar rats. Quantitative assessment of VP-immunopositive substance and digoxigenin-labeled VP mRNA (hybridization in situ) in neurosecretory cells of supraoptic (SON) and paraventricular (PVN) nuclei was performed using measurements of optical density of the stained substance in perykaria and a computer digital television analyzer with PhotoM software. Hybridization in situ technique allowed evaluating intensity of VP synthesis, while comparison of the amount of VP mRNA and VP-immunoreactive substance in neurons of SON and PVN made it possible to evaluate release of VP from perykaria. In PVN, repeated saline administration (0.25 ml per 100 g weight) and severe dehydration led to activation both of synthesis and of release of VP from cell perikarya. Use of -methyl-p-tyrosine, an inhibitor of catecholamine (CA) synthesis on the background of dehydration was not accompanied by changes of the functional state of VP-ergic neurons of PVN as compared with dehydrated animals. No changes in functional state of VP-ergic neurosecretory cells in SON were found after saline administration, whereas dehydration activated synthesis and release of VP from perykaria, like in VP-ergic neurons of PVN. Inhibition of CA synthesis on the background of dehydration led to activation of VP release by SON neurons without affecting the level of VP synthesis. The data obtained indicate that CA is able to suppress the VP release from neurons of SON, which is produced caused by activation of the VP-ergic system under conditions of dehydration.     

Participation of apoptotic proteins in hypothalamic regulation of volume of population of the red-backed vole <Emphasis Type=Italic>Clethrionomys rutilus</Emphasis>

The content of the antiapoptotic protein Bcl-2 and of the proapoptotic enzyme caspase-3 in the paraventricular nucleus (PVN) of sexually immature red-backed voles is studied in the course of the population cycle. The significant change of the Bcl-2 and procaspase-3 in the PVN neurons is established at all cycle phases. The low volume of population (under the most favorable conditions of the existence of the animals) is revealed to be characterized by the moderately increased or high expression of the Bcl-2 protein alongside with low or moderately increased caspase-3 activity. This is suggested to provide the PVN adequate reaction at the low population volume. At high population volume (under conditions of increased stress in the overcrowded population at the phase of peak and especially of fall), a significant decrease of the Bcl-2 expression is established with simultaneous increase of the caspase-3 activity. The disbalance in synthesis of apoptotic proteins seems to lead to disturbances of PVN functions at phases of peak and fall and, as a consequence, to a decrease of adaptive possibilities of these animals, which might be one of important causes of essential elimination of the animals at the autumn-winter period.     

Hemispheric Asymmetry in Prosody Perception by Healthy Subjects and Schizophrenic Patients

The interhemispheric interactions in perception of Russian prosody were studied in the norm and in schizophrenia as a clinical model of impaired hemispheric interactions. Monaural presentation of stimuli and binaural presentation in a free acoustical field were used. Sentences with main variants of Russian prosodic intonations were used as stimuli. The response time and the number of erroneous responses were recorded. In binaural listening without headphones, no significant difference in the percent of errors in identifying the emotional prosody was found between healthy subjects and schizophrenics. Compared with the healthy subjects, the patients made more errors in understanding the logical stress and fewer errors in understanding the syntagmatic segmentation. By response time, a significant dominance of the left ear was revealed in the healthy subjects during monaural listening to sentences with emotional prosody and complete or incomplete sentences, whereas no significant ear dominance was found in the schizophrenics. During monaural listening to sentences with logical stress, the response time was shorter when stimuli were presented to the right ear both in the healthy subjects and in the schizophrenics. The results testified that the functional brain asymmetry in schizophrenics is flattened. The flattening was less evident in the perception of a logical stress in a sentence and did not significantly affect the efficiency of identification of emotional prosody and syntagmatic segmentation of a sentence.     

Specialization of cerebral hemispheres in the perception of Russian intonations

Relations between the brain hemispheres were studied during the human perception of various types of Russian intonations. Fifty healthy subjects with normal hearing took part in the tests based on the method of monaural presentation of stimuli—the sentences that represented the main kinds of Russian emotional and linguistic intonations. The linguistic intonations expressed: various communicative types of sentences; completeness/incompleteness of a statement; various types of the syntagmatic segmentation of the statements; various logical stress. Sentences that required the identification of the emotion quality were used to study the perception of emotional intonations. The results of statistical analysis of latent periods and errors made by the test subjects demonstrated a significant preference of theright hemisphere in perceiving emotional intonations and complete/incomplete sentences; sentences with different logical stress were perceived mainly by theleft hemisphere. No significant differences were found in the perception of various communicative types of sentences and statements with different syntagmatic segmentation. The obtained data also testify to a difference in the degree of the involvement of human hemispheres in the perception and analysis of prosodic characteristics of the speech in males and females.     

A PET Study of the Brain Mechanisms Underlying Perception of Phrases with Syntagmatic Splitting

Positron emission tomography (PET) was used to localize the brain regions involved in the processing of pauses and intonation changes, which underlie the syntactically correct perception of auditory verbal stimuli. Subjects were asked to listen to a phrase and to choose a correct answer from two variants presented on a monitor screen. Differences in cerebral blood circulation were mapped for perception of phrases containing or lacking a pause determining the meaning. Conscious analysis of the phrase structure was associated with activation of the right lower prefrontal area and the right posterior medial area of the cerebellum. The possible role of these brain structures in analyzing factors of syntagmatic splitting is discussed.