Participation of Catecholamines and Nitric Oxide in Regulation of Apoptosis in Nonapeptidergic Neurons of the Rat Hypothalamus

The goal of this work was to study effects of blockade of catecholamine (CA) synthesis on activation of neuronal NO synthase (nNOS) and to elucidate the role of NO in activation of pro- and anti-apoptotic signal proteins in nonapeptidergic neurons of supraoptic (SON) and paraventricular (PVN) nuclei of hypothalamus. The experiment was carried out on adult male Wistar rats. Dehydration for 5 days was used as an apoptosis-activating factor in vasopressinergic neurosecretory cells of SON and PVN of hypothalamus in adult rats. To find out the role of CA, a part of the animals subjected to dehydration were administered intraperitoneally, for the last 3 consecutive experimental days, with an inhibitor of CA synthesis, -methyl-p-tyrosine (-MT) at a dose of 200 mg/kg body weight. A marker of the programmed cell death initiation, pro-apoptotic protein caspase-9, as well as anti-apoptotic protein bcl-2 and nNOS, were revealed using an immunohistochemical technique. Evaluation of immunopositive substance (nNOS, caspase-9, and bcl-2) in neurosecretory cells of SON and PVN were carried out quantitatively by determination of optical density of the stained material in perikarya, using a computerized digital television image analyzer and software PhotoM. On comparing the nNOS amount with the level of pro- and anti-apoptotic protein expression, we have come to the conclusion that a decrease of the brain CA level increases the nNOS and caspase-9 expression. This allows suggesting that an increased level of NO mediates activation of the pro-apoptotic protein caspase-9 and initiates apoptosis in neurons of SON and PVN of hypothalamus. The lack of neuronal loss in SON under conditions of decrease CA synthesis on the background of dehydration might be due to increased expression of the anti-apoptotic protein bcl-2, whose increased elevated level seems to prevent the further rise of the caspase-9 level and, thereby, protects cells from death. An increased level of bcl-2 in neurons of PVN correlated with high amounts of nNOS and caspase-9, but there also was observed no cell loss. It is suggested that suppression of apoptosis in PVN is due either to the bcl-2 effects at later stages of apoptosis, or to other mechanisms that inhibit active caspases.     

Participation of neuronal NO-synthase in regulation of hypothalamus vasopressinergic neurons of rat pups at early stages of postnatal ontogeny

To reveal character of interaction of catecholamines (CA) and NO in regulation of development and of the functional state of vasopressinergic (VP-ergic) neurons of supraoptic (SON) and paraventricular (PVN) nuclei, the female rats were injected intraperitoneally with the inhibitor of CA synthesis α-methyl-p-tyrosine, daily, from the 13th to the 20th days of pregnancy. Rat pups born by the females administered with saline at the same period of pregnancy as well as intact pups and adult rats were used as control. Expression of neuronal NO-synthase (nNOS) in neurons of SON and PVN of rat pups at early stages of postnatal development was found to be significantly higher than the definitive level, which allows suggesting participation of NO in development of hypothalamic VP-ergic neurons. The revealed differences of periods of the maximal nNOS expression in the SON and PVN neurons have permitted suggesting development of SON to be completed earlier than that of PVN. The pups exposed to stress at the last third of embryonic development had a long-lasting effect on the state of VP-ergic neurons of the pups after birth. The nNOS expression in neurons does not change, which suggests that NO is not involved in regulation of VP-ergic neurons after exposure to stress at early stages of ontogenesis. A decrease of CA level in the brain at the last third of embryogenesis led to a long preserved decrease of the functional activity of VP-ergic neurons. The nNOS expression in VP-ergic neurons of SON and PVN rose substantially under effect of a compensatory enhancement of tyrosine hydroxylase (TH) expression in neurons of SON and of an increase of the level of CA-ergic innervation of PVN. Thus, we have shown that a decrease of CA level in the embryonic brain leads to an increase of nNOS expression of hypothalamic VP-ergic neurons of rat pups after birth and that the character of NO action on function of VP-ergic neurons does not differ from that of adult animals as soon as at early stages of ontogenesis.     

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.     

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.     

Neurogenesis in the Hippocampus of Mice Exposed to Short-Term Hindlimb Unloading

Journal of Evolutionary Biochemistry and Physiology - Long-term spaceflights and simulated microgravity negatively affect the number of cognitive functions, including memory, learning, spatial...     

Role of Different Types of Adrenoreceptors in Regulation of Functional Activity of Vasopressinergic Neurosecretory Cells of Rat Hypothalamus

The goal of the present study was to find out by which adrenoreceptors noradrenaline affects synthesis and release of vasopressin from perikarya of neurosecretory cells in paraventricular and supraoptic nuclei of rat hypothalamus and what the character of this effect. In experiments in vitro with incubation of surviving hypothalamic slices in the medium containing noradrenaline or one of antagonists of adrenoreceptors (cirazoline—of ₁-, UK14304—of ₂-, cimaterol—of -adrenoreceptors) it was shown that application of different adrenoreceptor agonists resulted in different changes of the functional state of vasopressinergic cells in the supraoptic and paraventricular nuclei. Comparison of the content of vasopressin mRNA (method of hybridization in situ) and of vasopressin-immunoreactive substance (immunohistochemical method) has allowed us to conclude about different ratios of intensities of vasopressin synthesis and release in these cells under effects of noradrenaline and adrenoreceptor agonists studied. The results obtained indicate that noradrenaline has no effect on intensity of synthesis of vasopressin, but can inhibit its release from perikarya. Meanwhile, noradrenaline via ₁-adrenoreceptors is able to inhibit synthesis of vasopressin and, possibly, its release; via ₂-adrenoreceptors it also inhibits release of vasopressin, but does not affect its synthesis, whereas activation of -adrenoreceptors stimulates vasopressin synthesis by neurons of supraoptic and paraventricular nuclei of rat hypothalamus. The diversity of responses of vasopressinergic system to action of noradrenaline, which has been reported by many authors, seems to be due to predominant involvement of particular types of adrenoreceptors.     

Feedback control of human alpha rhythm from the central area.

Twenty subjects, aged 17 to 25, were given from 5 to 10 sessions of training in controlling alpha. They were divided into three groups, respectively reinforced for increasing alpha from the central area, reinforced for decreasing alpha from the central area, and given noncontingent reinforcement. Compared with the initial baseline, the alpha of the noncontingent subjects did not change, while those reinforced for increases were reliably higher and those reinforced for decreases reliably lower than the noncontingent group. A slight trend toward improvement during successive sessions was not reliable. Since the experiment was conducted in the Soviet Union, the subjects had no expectations of an "alpha experience." Although tests showed a slight elevation in mood at the end of the sessions, there were no differences among the groups. There was an increase in reports of fatigue after the training sessions. There were no reports of using visual or somatomotor maneuvers as a means of controlling alpha. Furthermore, alpha rhythm control was not found to be consistently correlated with changes in heart rate, respiration, or mood, as determined by cross-correlation analysis.     

<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