Appearance of parkinsonian syndrome after administration of delta sleep-inducing peptide into the rat substantia nigra

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.     

Neuro-pathophysiologic effects during primary hyperactivation of the bed nucleus of the stria terminalis in the rat brain

Penicillin administration into the bed nucleus of stria terminalis (BNST) in the rat brain caused epileptiform activity (EpA)--the formation of the generator of pathologically enhanced excitation (GPEE) in the nucleus. GPEE was registered during the first 3 days. EpA was also detected in the amygdala during 5-8 days, and in the hippocamp during the whole period of registration (2-3 weeks). There was the generalized enhancement of synchronized EpA in the range of 6-10 oscillations per s., in some cases with high-amplitude spindle (7-8 oscillations per s.). 50% of animals had emotional behavioural disorders, a marked fear reaction was observed for a month and more. Some animals demonstrated psychotic-like paroxysms with the elements of stereotypy accompanied by high-frequency low-amplitude EpA. It is suggested that when a primary GPEE in BNST is formed, the structures of septo-hippocampal system (BNST, amygdala, hippocamp) play a role of pathological determinants under the influence of which the pathological system consisting of a number of limbic and extrapyramidal structures is formed. Its activity is clinically manifested in the complex polymorphic neuropathological syndrome.     

Effects of verapamil on behavioral and microcirculatory disorders in pain syndrome of spinal etiology

In the experiments on Wistar rats with pain syndrome of spinal origin (PSSO) caused by the generator of pathologically enhanced excitation (GPEE) in dorsal horns of the spinal cord lumbosacral segments, it was shown that the intravenous verapamil injection (1.25 mg/kg) undoubtedly decreased behaviour response and improves the state of microcirculation. The compound of 10-fold decreased dose does not affect the behaviour response and microcirculation. When PSSO exists, the intravenous injection of analgin (150 mg/kg) produced an effect on the behaviour response and does not produce any action on microcirculation. When verapamil reaches the dorsal surface of the spinal cord (GPEE area) it decreases the behaviour response and microcirculation disorders created in PSSO. The obtained data make it clear that the GPEE depression caused by the verapamil calcium channel blocker weakens PSSO and normalizes the microcirculation.     

Parkinson syndrome after administration of acetylcholine into the caudate nuclei

Rats with the Parkinsonian syndrome induced by administration of acetyl choline and proserine into the rostral part of both caudate nuclei manifest an increased electrical activity (EA) in this part. Tremor, oligokinesia and rigidity are characterized by the appearance of paroxysmal EA with high amplitude of slow and rapid waves. The data obtained allow to conclude that neuropathophysiological basis of the Parkinsonian syndrome is the formation of the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei. Some peculiarities of the GPEE activity in tremor and akinetic rigidity syndromes were observed. Intrarostral administration of dopamine or intraperitoneal administration of cyclodol resulted in the inhibition of GPEE and disappearance of clinical manifestations of Parkinsonian syndrome.     

Changes in electric activity of neurons of dorsal raphe nuclei in the development of generator of pathologically enhanced excitation in the nociceptive system

In the experiments on rats it was proved by the method of extracellular registration of impulse neuron activity of dorsal raphe nucleus, that the formation of generator of pathologically enhanced excitation (GPEE) in nociceptive structures of spinal brain underlying the pain syndrome of spinal origin, results in a change of electric neuron activity of dorsal raphe nucleus. These changes are manifested by growing number of background nucleus neurons, the increase of middle frequency of discharges, and assuming pack character of impulse activity. These changes are greater marked in a ventral nucleus part, than in a dorsal one, which is evident of the activation of this antinociceptive system structure. The changes of electric activity of dorsal raphe neurons are stable for a long time after GPEE is formed in nociceptive system, and participate in suppression of GPEE and corresponding pain syndrome.     

Clinico-electroencephalographic indices of the parkinsonian syndrome induced by MPP+ in rats

The bilateral intranigral injection of 1-methyl-4-phenyl-pyridinium ion (MPP+) (10 g) produced significant oligokinesia, rigidity and weak tremor in rats. The extrapyramidal disturbances manifest a high-amplitude paroxysmal activity (PA) in the structures studied. It was found that the Pa was remarkable and more stable in the caudata nucleus than in other brain structures. It is PA that gives us the real basis to conclude the formation of the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei. The analysis of PA dynamics revealed that the formation of the GPEE in the caudata nuclei correlated with development of parkinsonian syndrome (PS).     

Effect of the spinal pain syndrome on pain reactions caused by nociceptive thermal stimuli

It has been shown that the reaction of both limbs to thermal pain stimulation was suppressed during spinal pain syndrome development caused by generators of pathologically enhanced excitation (GPEE) formed in the dorsal horns of the spinal cord lumbosacral segments on one side. The analgetic effect on physiological pain was retained long after pain syndrome disappearance (48 hours), the effect was bilateral and was independent of the type of agent producing GPEE. It was shown that neuronal activity in the antinociceptive system key structure (nucleus raphe dorsal) increases. It is assumed that physiological pain relief is caused by enhanced activity in antinociceptive system structures in pain syndrome.     

Emotional behavior disorders in rats during the formation of a generator of pathologically enhanced excitation in the basomedial nuclei of the amygdaloid complex

Microinjections of kainic acid and ferrous sulfate into basomedial nuclei of both amygdalae resulted in the formation of the generator of pathologically enhanced excitation (GPEE), as evidenced by the epileptical activity (EpA) registered in both nuclei. EpA of different intensity and pattern could be retained for more than three weeks. Hyperactive basomedial nuclei played the role of a primary pathological determinant which caused the complex of emotional and behavioural disorders. Continuous motor depression at the early stages alternated pathologically enhanced activity at the later stages. A number of signs could be considered as the evidence of the affective disorders (motivation suppression, enhanced irritation, anxious excitation). Stereotype behaviour, immobility, rigidity, different types of vegetative disorders (ptosis, constipation, piloerection, loss of weight, respiratory arrhythmia, dystrophic symptoms) were observed in most animals. The emotional, behavioural and vegetative disorders described are compared to the manifestations of the depressive syndrome.     

Modeling of torsion dystonia through electric stimulation of the vermis cerebellum cortex

It was shown in acute experiments on cats that electrical stimulation (ES) (100-300 Hz, 5.0-10.0 V) of cat's cerebellar vermal cortex (lobules V and VI) was followed by head deviation in the direction opposite to that side on which the animal was laying, posture and movement disturbances and also by simultaneously occurred contraction of musculus-antagonists of extremities. The tonic and posture disturbances were observed during 40-60 s after ES cessation. During this time in the zone of ES in cerebellar cortex the high-amplitude synchronized activity was registered which was due to generator of pathologically enhanced excitation (GPEE) formation. Intraperitoneal diazepam (0.5-1.0 mg/kg, 30 min before the observation) pretreatment suppressed GPEE formation that correlated with suppression of syndrome manifestations. The conclusion was made that cerebellar hyperactive cortex, which was due to GPEE induction, might have played the role of pathological hyperactive determinant structure of the described syndrome.     

Effects of difenin on experimental parkinsonian syndrome

The aim of this study was to investigate the effect of difenin on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesis and rigidity followed by the high amplitude slow and rapid waves in the CN and in sensorimotor cortex (SC). The changes of the electrical activity in the CN were more prominent then in SC. I.p. injection of difenin (20 mg/kg) resulted in an increase of motor activity and decrease of rigidity in rats. The reduction of extrapyramidal symptoms were correlated with at the inhibition of GPEE in the CN. These data suggest that difenin can be a part of the complex pathogenetic therapy of parkinsonian syndrome.     

Effects of intranasally administered substance P in parkinsonian syndrome]

The effect of intranasal substance P injection on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in caudate nuclei (CN) was investigated. MPTP or reserpine administration in old rats induced oligokinesia, rigidity and tremor followed by the high amplitude slow and rapid waves in both CN. The bilateral intranasal injection of substance P (25 micrograms/kg) resulted in an increase in motor activity and almost completely abolished the rigidity and tremor. The reduction of extrapyramidal symptoms was considered as a result of the inhibition of GPEE in CN. The possibility of substance P entry from nasal cavity into the brain was discussed. The changes of the substance P balance in nigrostriatal system was suggested to be on of the pathogenetic links of parkinsonian syndrome.     

Effects of substance P on experimental parkinsonian syndrome

The aim of this study was to investigate the effect of substance P (SP) on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesia and rigidity followed by the high amplitude slow and rapid waves in both CN. The changes of electrical activity in CN were more prominent than in the sensorimotor cortex. The bilateral intracaudate injection of SP (5 micrograms) resulted in an increase in motor activity and almost completely abolished the rigidity. The reduction of extrapyramidal symptoms was considered as a result of the inhibition of GPEE. The changes of the SP balance in nigro-striatal system was suggested to be one of the pathogenetic links of parkinsonian syndrome.     

Apoptosis during sexual differentiation of the bed nucleus of the stria terminalis in the rat brain

The bed nucleus of the stria terminalis (BST) in the rat forebrain differs between males and females. To test whether apoptosis may contribute to the development of sex differences in the BST, the incidence of apoptosis was determined in sham-treated males and sham-treated females sacrificed on postnatal days (PN) 2, 4, 6, 8, 10, and 12 (PN 1 being day of birth). More apoptotic nuclei were found in the principal nucleus of the BST (BSTpr) in females than in males, whereas the reverse was true for the lateral division of the BST (BSTl). Moreover, the volume of the BSTpr was larger in males than in females, whereas there was no sex difference in the volume of the BSTl. Our results also confirmed earlier reports indicating that the incidence of apoptosis in the central part of the medial preoptic nucleus (MPNc) is higher in females than in males. No sex difference in apoptosis was found in the ventromedial hypothalamus (VMH) and paraventricular nucleus (PVN). The volume of the MPNc and VMH was larger in males than in females, whereas the PVN volume did not differ between males and females. To test whether sex differences in neonatal levels of gonadal steroids may cause sex differences in the incidence of apoptosis in the BSTpr, the incidence of apoptosis was compared between castrated males and females that were treated with testosterone propionate or vehicle on the day of birth. In the BSTpr of gonadal steroid-treated animals, the incidence of apoptosis was lower when compared to animals treated with vehicle, which was also true for the MPNc. These results are consistent with the hypothesis that gonadal steroids contribute to the sexually dimorphic differentiation of the BST by controlling the incidence of apoptosis.     

Studies on extrahypophyseal sites of estrogen action in the induction of ovulation in rats.

To discover possible extrahypophyseal sites of estrogen action in the induction of ovulation, the influence of a s.c. injection of estradiol benzoate (EB) on cell nuclear sizes in the limbic-medial preoptic continuum of progesterone-pretreated cyclic rats was evaluated. The ovulatory dose of 5 mug EB caused a significant increase of nuclear volumes in the medial preoptic nucleus and the anterior and posterior parts of the medial amygdaloid nucleus. Precocious ovulation was induced in prepuberal female rats by unilateral implantation of a molten EB: cholesterol mixture into the posterior part of the mediocortical amygdala (PMCA), but not by implantation into the anterior part of this region (AMCA) or the medial preoptic area (MPA). In adult females injected s.c. with 2.0 mg progesterone on the day post estrus, bilateral implantation of 0.1 or 0.2 mug crystalline EB on the following day did not abolish the delaying effect of progesterone on the preovulatory LH increase and ovulation, when the implants were located in the MPA, lateral septum (LS), bed nucleus of the stria terminalis (BST), AMCA, PMCA or dorsal hippocampus (DHPC), whereas intrapituitary implants were highly effective. However, the bilateral introduction of large tallow pellets containing 0.1 mug EB each, into the LS, BST, AMCA or PMCA advanced ovulation in rats with progesterone-induced 5-day cycles. Equal pellets did neither induced ovulation nor an LH increase after implantation into the MPA or the DHPC. The results suggest that the anterior pituitary, mediocortical amygdala, BST and LS, but not the MPA or DHPC, are sites of the stimulatory feedback of estrogen on gonadotropin secretion in female rats, and that the amygdaloid response to estrogen differs between prepuberal and cyclic females.     

Role of cytokines in immune response to T-independent antigens, type 2

The influence of human and mouse cytokines on the induction of immune response to model T-independent (TI) antigens of type 2--DNP-dextran and DNP-ficoll--in the culture of mouse spleen cells was studied. For the first time this study revealed that the action of definite T-cell factors not only induced the polyclonal stimulation of B lymphocytes, but also the increased synthesis of specific antibodies, as well as switched over antibody isotypes from IgM to IgG. This confirmed the suggestion that T cells took part (directly or indirectly) in the regulation of immune response to so-called TI antigens. These results widened our knowledge on the mechanisms of the development of humoral immune response to TI antigens of type 2.     

Effects of hypercapnia on Breuer-Hering threshold for inspiratory termination

The effects of CO2 concentration on the timing of inspiratory duration (TI) and expiratory duration (TE) and the responses to lung inflation were studied in decerebrate paralyzed cats. With lung volume held at functional residual capacity during the breath cycle, hypercapnia (fractional concentration of inspired CO2 = 0.04) caused variable changes in TI and significant increases in TE. To obtain the Breuer-Hering threshold relationship [tidal volume (VT) vs. TI] and the timing relationship between TE and the preceding TI (TE vs. TI), ramp inflations of various sizes were used to terminate inspiration at different times in the breath cycle. Hypercapnia caused the VT vs. TI curves to shift in an upward direction so that at higher lung volumes TI was lengthened. Also, the slope of the TE vs. TI relationship was increased. The results suggest that hypercapnia diminished the sensitivity of the Breuer-Hering reflex to the lung volume, thus allowing volume to increase with little effect on TI. In addition, TE appears to become more sensitive to changes in the preceding TI. A model is presented which provides a possible neural mechanism for these responses.     

BST2/Tetherin Inhibits Dengue Virus Release from Human Hepatoma Cells

Type I interferons (IFN) have been shown to play an important role for inhibiting Dengue virus (DENV) infection. Identifying IFN-induced cellular proteins are essential for understanding its mechanisms against DENV. Here we established stable Huh7-derived cell lines expressing the IFN-induced cell membrane protein BST2 (Huh7-BST2) or its variant bearing a V5 tag at the C-terminal (Huh7-BST5CV5). These cell lines were infected with DENV to determine proteins modulating their anti-DENV response. We found that expression of BST2 did not affect the efficiency of DENV infection and intracellular replication. Rather, it significantly reduced the virion yield of the infected cells, particularly at low MOI infection. In addition, BST2 also decreased the foci formation and the size of infectious foci in cultured Huh7 monolayers with media containing methocellulose. The addition of the V5 tag at C-terminal inhibited the GPI modification of BST2 and blocked its shift from endoplasm to cytoplastic membrane. BST2CV5 did not affect DENV infection and foci formation in Huh7 cells but reduced virion yield by 1 log at low MOI infection. Interestingly, intracellular BST2CV5 expression was reduced by high level of DENV production.

Conclusion

Our results imply that BST2 is a functional mediator of the IFN response against DENV infection. BST2 inhibits the release of DENV virions from Huh7 cells and limits viral cell-to-cell transmission. BST2CV5 variant is unable to inhibit DENV release but impairs viral infection in cells.     

Efficiency of thermoregulatory system in man under endogenous and exogenous heat loads

The aim of the present work was to estimate the dynamics and efficiency (eta sw) of sweating, and thermoregulatory index (TI) defined as a ratio of heat loaded the body to the heat removed to the environment. In the first part of this work 22 men exercised with an intensity of 50% VO2 max. in 22 degrees C, 16 men were exposed to 40 degrees C at rest, and 9 men exercised at the level of 50% VO2 max. at 30 degrees C. In the second part, 8 men and 8 women were exposed to 40 degrees C before and after dehydration (1% of body mass, approximately), 8 men exercised at 23 degrees C before and after hyperhydration (35 ml/kg of body mass) and 22 men exercised before and after 3 months of endurance training. Body heat balance, rectal (Tre), tympanic (Tty) and mean skin (Tsk) temperatures were measured in all subjects. TI was greater during simultaneous (0.84) than during separate endo- (0.76, p less than 0.01) or exogenous (0.67, p less than 0.001) heat loads. The respective values of eta sw were 0.82; 0.57 (p less than 0.001) and 0.78 (p less than 0.001). No difference in TI was found between men and women. Dynamics of sweating was greater in men but efficiency of sweating was greater in women. Dehydration before heat exposure decreased both dynamics of sweating and TI but it increased eta sw in men. As a result Tre was greater in dehydrated (0.45 degrees C) than in normally hydrated men (0.31 degrees C, p less than 0.002). Dehydration did not affect the measured variables in women. Hyperhydration of exercising men caused an increase in TI from 0.72 to 0.82 (p less than 0.05) and in eta sw from 0.57 to 0.81 (p less than 0.01). In men exercising after endurance training the onset of sweating was shortened from 4.0 to 0.9 min (p less than 0.002). TI increased from 0.76 to 0.89 (p less than 0.001), eta sw increased from 0.57 to 0.74 (p less than 0.02) whereas Tty was lower (1.10 and 0.58 degrees C, p less than 0.001, respectively). It is concluded that dynamics and efficiency of sweating, as well as the thermoregulatory index depend on the type of heat load. Men and women tolerate dry heat equally well. Dehydration changes thermoregulatory function in men but not in women. Hyperhydration before exercise and particularly endurance training increase tolerance of endogenous heat.(ABSTRACT TRUNCATED AT 400 WORDS)     

Projection from the ventral bed nucleus of the stria terminalis to the retrorubral field in rats and the effects of cells in these areas on mating in male rats versus gerbils

This research identified the rat counterpart of the lateral cell group of the sexually dimorphic area (SDA) found in medial preoptic area (MPOA) gerbil of gerbils. The lateral SDA (lSDA) is critical for mating in male gerbils and contains most of the SDA cells projecting to the retrorubral field (RRF), a projection that is also important for mating. Therefore, to locate the counterpart of the lateral SDA, we traced the inputs to the rat RRF, which were dense in the ventral part of the bed nucleus of the stria terminalis (BST). To determine if the ventral BST or its projection to the RRF affects mating in male rats, we disrupted them bilaterally by placing cell-body lesions bilaterally in the ventral BST or unilaterally there and in the contralateral RRF. We also studied the effects of RRF lesions in both rats and gerbils. Bilateral ventral BST lesions, which left the medial preoptic nucleus intact, produced persistent and severe mating deficits. Disconnecting the ventral BST from the RRF also had long-lasting, but less severe, consequences. RRF lesions produced only temporary mating deficits in rats, but virtually eliminated mating in gerbils. The recovery of mating in rats after RRF, but not ventral BST, lesions, and the intermediate effects of disconnecting these areas from each other suggest that the ventral BST may contain mating-related projection neurons other than those projecting to the RRF or that its RRF-projecting cells send collaterals to another site. In either case, the pedunculopontine tegmental nucleus or raphe nuclei may be involved.     

Differential effects of ballistic versus sensorimotor training on rate of force development and neural activation in humans

Balancing exercises on instable bases (sensorimotor training [SMT]) are often used in the rehabilitation process of an injured athlete to restore joint function. Recently it was shown that SMT was able to enhance rate of force development (RFD) in a maximal voluntary muscle contraction. The purpose of this study was to compare adaptations on strength capacity following ballistic strength training (BST) with those following an SMT during a training period of 1 microcycle (4 weeks). Maximum voluntary isometric strength (MVC), maximum RFD (RFDmax) and the corresponding neural activation of M. soleus (SOL), M. gastrocnemius (GAS), and M. tibialis anterior (TIB) were measured during plantar flexion in 33 healthy subjects. The subjects were randomly assigned to a SMT, BST, or control group. RFDmax increased significantly stronger following BST (48 +/- 16%; p < 0.01) compared to SMT (14 +/- 5%; p < 0.05), whereas MVC remained unchanged in both groups. Median frequencies of the electromyographic power spectrum during the first 200 ms of contraction for GAS increased following both BST (45 +/- 21%; p < 0.05) and SMT (45 +/- 22%; p < 0.05), but median frequencies for SOL increased only after SMT (13 +/- 4%; p < 0.05). Additionally, mean amplitude voltage increased following BST for SOL (38 +/- 12%; p < 0.01) and for GAS (73 +/- 23%; p < 0.01) during the first 100 ms, whereas it remained unchanged after SMT. It is concluded that BST and SMT may induce different neural adaptations that specifically affect recruitment and discharge rates of motor units at the beginning of voluntary contraction. Specific neural adaptations indicate that SMT might be used complementarily to BST, especially in sports that require contractile explosive properties in situations with high postural demands, e.g., during jumps in ball sports.