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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine (NE), on the long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 system was examined in urethane-anesthetized rats, the objective being to determine whether or not this drug acts as NE on the LTP. L-threo-DOPS may be effective for treating some type of mental disorders, including dementia. The LTP, induced in CA3 by tetanic stimulation (100 Hz for 1 s) applied to the mossy fiber persisted for more than 4 h. When L-threo-DOPS (50 and 150 micrograms) was injected into the lateral ventricle 30 min prior to the tetanic stimulation, there were no significant alterations in the LTP. However, in animals treated with reserpine (5 mg/kg i.p.) 24 h before the experiment, LTP was not induced with tetanic stimulation alone yet was obtained when tetanic stimulation was preceded by L-threo-DOPS (50 and 150 micrograms) applied to the ventricle. The LTP obtained by L-threo-DOPS in the reserpine-treated animal was inhibited by pretreatment with benserazide and was completely blocked by the simultaneous administration of sotalol. These results suggest that NE converted from L-threo-DOPS plays an important role in inducing LTP in the mossy fiber-CA3 system in the animals deficient in catecholamines.

Anesthesia↗
PubMed1991

Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis.

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.

Animals↗
PubMed1991

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices.

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK-602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers.

Animals↗
PubMed1991

Inhibition of lateral vestibular nucleus neurons by 5-hydroxytryptamine derived from the dorsal raphe nucleus.

Electrophysiological studies were performed to elucidate the effect of 5-hydroxytryptamine (5-HT) originating in the dorsal raphe nucleus (DR) on neuronal activity in the lateral vestibular nucleus (LVN) neurons, using cats anesthetized with alpha-chloralose. LVN neurons were classified into monosynaptic and polysynaptic neurons according to their responses to vestibular nerve stimulation. Conditioning stimuli applied to the DR inhibited orthodromic spikes elicited by vestibular nerve stimulation predominantly in polysynaptic neurons of the LVN. The iontophoretic application of 5-HT also inhibited orthodromic spikes of the LVN neurons. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretically applied 5-HT in the same neurons. These inhibitions with both treatments were antagonized during the application of methysergide, a 5-HT antagonist. In the majority of LVN polysynaptic neurons that responded to antidromic stimulation of the ipsilateral or contralateral abducens nucleus, orthodromic spikes elicited by vestibular nerve stimulation were inhibited by DR conditioning stimulation and the iontophoretic application of 5-HT. In contrast, LVN neurons that responded to antidromic stimulation of the vestibulospinal tract were rarely affected by these treatments. These results indicate that 5-HT derived from the DR inhibits the synaptic transmission of LVN polysynaptic neurons ascending to the abducens nucleus, and suggest that 5-HT derived from the DR is involved in the regulation of the vestibulo-ocular reflex.

Abducens Nerve↗
PubMed1991

Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats.

The effects of thyrotropin-releasing hormone (TRH) were investigated on absence-like seizures, which are characterized by the sudden appearance of 5-7 Hz spike-wave-like complexes in the cortical and hippocampal EEG, and on tonic convulsions of spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant obtained by mating zitter homozygote (zi/zi) with tremor heterozygote rats (tm/+). TRH (5 and 10 mg/kg i.v.) inhibited the appearance of both absence-like seizures and tonic convulsions of SER without inducing obvious changes in the background EEG. The inhibitory effects were seen 5-20 min after injection of 10 mg/kg TRH and were antagonized by pretreatment with haloperidol (0.5 and 1.0/kg i.p.), although haloperidol alone did not affect the seizures. These results suggest that TRH has an antiepileptic effect in the genetically defined animal model, SER, and that the effect is mediated by the central dopaminergic system.

Animals↗
PubMed1991

Correlation between estrogen receptor status and histological malignancy in human breast cancer.

Sixty-two breast carcinoma patients underwent mastectomy and were analyzed for correlations between estrogen receptor (ER) status of the tumor and the histological findings of tumor, age, nodal status, and tumor size. An immunocytochemical assay for the detection of ER in breast carcinomas was used to evaluate the staining intensity index (SII) of the ER level of the tumors, which was calculated from the staining intensity of cancer cells and the percentage of ER-positive cancer cells. The histological differentiation of carcinomas showed a strong correlation with the SII. A statistically significant (F = 10.580, P less than 0.0005) negative correlation was found between the grade of malignancy and the SII. Patients under 50 years of age tended to have a lower SII, whereas patients over 49 years of age tended to have a higher SII. The tumor size, and nodal status showed no correlations with the SII in any of the patients. The histological differentiation of the tumor cells showed a strong correlation with the heterogeneity of the distribution of ER-positive cells in breast cancers.

Adult↗
PubMed1991

Short- and long-term effects of transection of the ophthalmic nerve on optokinetic nystagmus in the rabbit.

The role of extraocular proprioception in optokinetic nystagmus (OKN) was examined, using adult pigmented rabbits following transection of the ophthalmic branch of the trigeminal nerve. OKN was induced by rotation of a drum at an angular velocity of 0.85 and 3.7 degrees/s. The eye on the operated side showed a delay in the transition from the OKN-induced quick phase to the slow phase regardless of closure of the eye on either the operated or unoperated side. In addition, the eye on the operated side showed an anticompensatory response in the vestibulo-ocular reflex (VOR) with an unstable drift in the dark. The above abnormalities in OKN and VOR following rhizotomy disappeared after 1-1.5 months. These results suggest that proprioception in the extraocular muscle plays an important role in the fine regulations of eye position for gaze accuracy. The recovery demonstrated appears to be due to a compensatory mechanism in the central nervous system.

Animals↗
PubMed1991

Inhibition by talipexole, a thiazolo-azepine derivative, of dopaminergic neurons in the ventral tegmental area.

A microiontophoretic study using rats anesthetized with chloral hydrate and immobilized with gallamine triethiodide was carried out to compare the effect of talipexole (B-HT 920 CL2:2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine-dihydrochloride), a dopamine autoreceptor agonist, on dopaminergic neurons in the ventral tegmental area (VTA) to non-dopaminergic neurons in the VTA. VTA neurons were classified into two types according to the responses to antidromic stimulation of the nucleus accumbens (Acc): type I neurons with a long spike latency (8.69 +/- 0.24 msec) upon Acc stimulation and low spontaneous firing rate (6.80 +/- 1.34/sec), and type II neurons with a short latency (2.76 +/- 0.20 msec) and high spontaneous firing rate (26.77 +/- 7.05/sec), probably corresponding to dopaminergic and non-dopaminergic neurons, respectively. In type I neurons, microiontophoretic application of talipexole and dopamine inhibited antidromic spike generation elicited by Acc stimulation, and talipexole-induced inhibition was antagonized by domperidone (dopamine D-2 antagonist). In type II neurons, however, the antidromic spikes were not affected by either talipexole or dopamine. Furthermore, spontaneous firing was also inhibited by iontophoretically applied talipexole and dopamine in most type I neurons, but rarely affected by either drug. Inhibitory effects of talipexole were antagonized by domperidone. These results suggest that talipexole acts on dopamine D-2 receptors, thereby inhibiting the dopaminergic neurons in the VTA.

Animals↗
PubMed1991

Dopamine D-1 receptor-mediated inhibition of nucleus accumbens neurons from the ventral tegmental area.

1. Spike generation by stimulation of the parafascicular nucleus of thalamus was extracellularly recorded in the nucleus accumbens of chloral hydrate-anesthetized adult Wistar rats using a silver-wire microelectrode attached along a seven-barreled micropipette, each of which was filled with dopamine, SKF 38393 (D-1 agonist), bromocriptine (D-2 agonist), haloperidol, SCH 23390 (D-1 antagonist) and domperidone (D-2 antagonist). The drugs were microiontophoretically applied to the target neurons recorded. 2. Effects of dopamine receptor antagonists on the inhibition of the spike generation by conditioning stimuli applied to the ventral tegmental area preceding the test stimulus to the parafascicular nucleus and those of dopamine agonists on the test stimulus-induced spikes were examined. 3. The parafascicular nucleus stimulation-induced spikes were inhibited by dopamine as well as D-1 and D-2 agonists and by the conditioning stimulation of the ventral tegmental area. The conditioning stimulation-induced inhibition was antagonized by haloperidol and SCH 23390, but not by domperidone. 4. Activation of D-1 receptors, which make probably synaptic contact with dopaminergic nerve terminals from the ventral tegmental area, is considered to result in inhibition of the neuronal activity of the nucleus accumbens neurons receiving input from the parafascicular nucleus of the thalamus. In addition, D-2 receptors located extrajunctionally may be involved in the inhibition of the same neurons in the nucleus accumbens.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Effects of anti-vertigo drugs on medial vestibular nucleus neurons activated by horizontal rotation.

The effects of anti-vertigo drugs on medial vestibular nucleus (MVN) neurons were examined to assess the site and mode of action using cats anesthetized with alpha-chloralose. Single neuron activity in the MVN was extracellularly recorded using a silver wire microelectrode attached along a seven-barreled micropipette, each of which was filled with diphenhydramine, diphenidol, betahistine, glutamate or NaCl. Type I of the MVN neurons were identified according to the responses obtained when the animal placed on a turn-table was rotated sinusoidally. The effects of the drugs were examined on type I neurons which received impulses primarily from the labyrinth and sent them to the oculomotor nuclei. The microiontophoretic application of diphenhydramine, diphenidol and betahistine inhibited rotation-induced firing of type I MVN neurons. Diphenhydramine and diphenidol were more potent than betahistine. These results suggest that these drugs directly act on MVN neurons to reduce the responsiveness to rotatory stimulation.

Animals↗
PubMed1991

Ontogeny of absence-like and tonic seizures in the spontaneously epileptic rat.

The ontogeny of epileptic seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) was studied by examining behaviour and electroencephalogram (EEG) simultaneously. Weight gain and survival time were also studied. Compared with the control Kyo:Wistar rats, SER showed a much smaller increase in body weight. All male and female SER died before 20 and 18 weeks of age, respectively. Body tremor was observed at 2 weeks of age but disappeared after 11 weeks. Staggering gait appeared after 7 weeks of age, and intensified with age. Absence-like seizures characterized by paroxysmal appearance of 5-7 Hz spike-wave-like complexes were observed in the cortical or hippocampal EEG after 5 weeks of age, and tonic seizures with low voltage fast waves were observed after 6 weeks of age. All SER exhibited both absence-like and tonic seizures with high frequencies from 12 weeks of age. Differences with other spontaneous rat models of epilepsy and application methods for estimating seizure-inhibitory effects of anti-epileptic drugs are discussed.

Animals↗
PubMed1990

Inhibition by enkephalin of medial vestibular nucleus neurons responding to horizontal pendular rotation.

Electrophysiological studies were performed to determine whether or not enkephalin modulates the activities of medial vestibular nucleus (MVN) neurons responding to horizontal pendular rotation using alpha-chloralose anesthetized cats. The effects of microiontophoretically applied drugs were examined in type I and type II neurons identified according to responses to horizontal, sinusoidal rotation; type I and type II neurons showed an increase and decrease in firing with rotation ipsilateral to the recording site and vice versa with contralateral rotation, respectively. Iontophoretic application of enkephalin suppressed spike firing induced by rotation of the animals in type I neuron, but not in type II neuron. The spike firing induced by iontophoretically applied glutamate was also inhibited during the application of enkephalin. The inhibition by enkephalin of both rotation- and glutamate-induced firing was antagonized by naloxone which was given simultaneously. These results suggest that enkephalin acts on MVN type I neuron to inhibit transmission from the vestibule, thereby controlling vestibulo-ocular reflex.

Animals↗
PubMed1990

D-2 receptor-mediated inhibition by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392), of dopaminergic neurons in the ventral tegmental area.

A microiontophoretic study was performed to investigate the effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl) piperazinyl) propoxy] 2-(1H)-quinolinone (OPC-4392), on neuronal activities of the ventral tegmental area (VTA) of rats anesthetized with chloral hydrate. The VTA neurons, which were identified by antidromic stimulation of the nucleus accumbens (Acc), were classified into type I and type II neurons according to the responses to Acc stimulation: type I neurons had a long spike latency of over 7 msec (9.63 +/- 0.25 msec), and the type II, a short latency of less than 7 msec (2.98 +/- 0.27 msec) upon Acc stimulation. In all of 11 type I neurons, iontophoretically applied OPC-4392 and dopamine inhibited the antidromic spikes elicited by Acc stimulation. This inhibition was antagonized by simultaneous application of domperidone (dopamine D-2 antagonist). However, in 16 out of 19 type II neurons the antidromic spikes were not affected by either OPC-4392 or dopamine. When the effects of iontophoretically applied OPC-4392 and dopamine on spontaneous firings were tested in 32 VTA neurons identified by Acc stimulation (including type I and type II neurons), there was a relationship between the effects of these two drugs. These results suggest that OPC-4392 acts on dopamine D-2 receptors of the dopaminergic neurons in the VTA, thereby inhibiting neuronal activity.

Animals↗
PubMed1990

Alpha 1-adrenergic receptor-mediated excitation from the locus coeruleus of the sacral parasympathetic preganglionic neuron.

Electrophysiological studies using alpha-chloralose anesthetized cats were performed to elucidate whether or not noradrenaline derived from the locus coeruleus (LC) activates sacral intermediolateral (IML) cell column neurons, from which the sacral parasympathetic neurons originate. LC stimulation induced a spike in the sacral IML cell column neurons (parasympathetic interneurons), which were not antidromically activated by stimulation of the pelvic nerve, with a mean latency of 65.4 +/- 4.64 msec (mean +/- S.E., n = 12). In the sacral IML cell column neurons (parasympathetic preganglionic neurons), which were antidromically activated by pelvic nerve stimulation with a mean latency of 5.32 +/- 1.23 msec, LC stimulation also elicited a spike with the mean latency of 67.9 +/- 4.53 msec (n = 7). Iontophoretic application of prazosin, an alpha 1-adrenergic blocking agent, inhibited spikes elicited by LC stimulation in 8 of 12 sacral parasympathetic interneurons tested, but no alterations of LC stimulation-induced spikes were seen during iontophoretic application of sotalol, a beta-blocking agent. In contrast, spikes elicited by LC stimulation in the sacral parasympathetic preganglionic neurons tested were not affected by iontophoretic application of either prazosin or sotalol. These results suggests that noradrenaline derived from the LC activities the parasympathetic interneurons in the sacral IML cell column through alpha 1-adrenergic receptors, thereby inducing excitation of the sacral parasympathetic neurons receiving impulses from the interneuron.

Animals↗
PubMed1990

Inhibition of hippocampal CA1 neurons by 5-hydroxytryptamine, derived from the dorsal raphe nucleus and the 5-hydroxytryptamine1A agonist SM-3997.

Electrophysiological studies, using chloral hydrate-anesthetized rats, were undertaken to determine whether hippocampal pyramidal neurons, receiving input from the medial septal nucleus, were affected by 5-hydroxytryptamine (5-HT) derived from the dorsal raphe nucleus. The pyramidal neurons in the CA1 region of the hippocampus were classified into short- and long-latency neurons, based on their response to stimulation of the medial septal nucleus. Microiontophoretically applied atropine inhibited the generation of spikes upon stimulation of the medial septal nucleus in short-latency neurons, but had no effect on long-latency neurons. In the short-latency neurons, the stimulation-induced spikes of the medial septal nucleus were inhibited by conditioning stimuli applied to the dorsal raphe nucleus and iontophoretic application of 5-HT and the 5-HT1A agonists, SM-3997 (3 a alpha,4 beta,7 beta,7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate) and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin). The conditioning effect of the dorsal raphe nucleus was antagonized by methysergide. However, in the long-latency neurons, the spikes elicited by stimulation of the medial septal nucleus were not affected by the conditioning stimulation of the dorsal raphe nucleus, or iontophoretically applied 5-HT. These results indicate that 5-HT, originating in the dorsal raphe nucleus inhibited hippocampal pyramidal neurons receiving cholinergic input from the medial septal nucleus, but not those receiving non-cholinergic input from the medial septal nucleus. The drug SM-3997 inhibited the activity of hippocampal pyramidal neurons, that receive excitatory cholinergic input from the medial septal nucleus by acting on 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Mediation of micturition reflex by central norepinephrine from the locus coeruleus in the cat.

We examined whether norepinephrine originating in the locus coeruleus mediates the micturition reflex in anesthetized cats. 6-Hydroxydopamine, a catecholamine neurotoxin, injected bilaterally into the locus coeruleus markedly decreased catecholamine fluorescence in the lesioned area and induced urinary retention after 72 to 84 hr. At this time, there was no or only slight contraction of the urinary bladder induced by its distension, while the contraction was noted before the treatment. However, phenylephrine, an alpha 1-receptor agonist, applied intrathecally in 6-hydroxydopamine-treated animals induced moderate bladder contraction. In sham-operated animals, the bladder contraction on its distension was inhibited by intrathecally applied prazosin, an alpha 1-receptor antagonist. Thus, in the micturition reflex, norepinephrine derived from the locus coeruleus acts on the alpha 1-adrenergic receptors in the sacral cord, and induces urinary bladder contraction via activation of the sacral parasympathetic preganglionic neurons.

Animals↗
PubMed1990

Inhibition by intravenously administered sodium bicarbonate of neuronal activity in medial vestibular nucleus neurons.

The effects of 7% sodium bicarbonate on medial vestibular nucleus (MVN) neurons were examined to elucidate the mechanism underlying its anti-vertigo action, using alpha-chloralose-anesthetized cats. Intravenous injection of the drug at 1, 2 and 4 ml/kg every 10 min dose-dependently inhibited rotation- and glutamate-induced firing of type 1 neurons, although a low dose of the drug enhanced firing in a few neurons. However, microiontophoretic application of bicarbonate ions did not inhibit rotation- or glutamate-induced firing. After injection of the drug, the Po2 level in arterial blood did not differ from previous levels, but the bicarbonate ion levels dose-dependently increased concomitantly with an increase in pH, as compared with previous levels. These results suggest that the intravenous injection of 7% sodium bicarbonate directly inhibits the neuronal activity of the MVN, although the lower dose may enhance neuronal activity by acting on the peripheral vestibule.

Animals↗