Taketsugu Minami

17β-Estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP

The process by which 17β-estradiol rapidly modulates the excitability of neurons in the ventromedial hypothalamus, a facilitation center of female sexual behavior and satiety center of feeding behavior, through mediation by cyclic nucleotides, was investigated by intracellular recording from the guinea pig brain slice preparations. Two types of short-term responses were produced by depolarization with decreased K+ conductance and hyperpolarization with increased K+ conductance. These two responses were enhanced by the phosphodiesterase inhibitor, isobutylmethylxanthine. However, the specific adenylate cyclase activator, forskolin, enhanced only the depolarization. The analogue of cyclic adenosine 3′,5′-monophosphate (cAMP), 8-bromo-cAMP, induced only depolarization, the ionic mechanism of which was similar to that of 17β-estradiol. In addition, the possibility of non-specific effects of cyclic nucleotides was precluded by an experiment using an analogue of cyclic guanosine 3′,5′-monophosphate (cGMP), 8-bromo-cGMP, which hyperpolarized neurons. Thus, the present study strongly suggests that the production of depolarizing responses of neurons in the hypothalamus produced by estradiol is specifically mediated through cAMP.

The effects of noradrenaline on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

1. Intracellular recordings were made from vagal motoneurones identified by antidromic stimulation in the dorsal motor nucleus of the vagus (d.m.v.) in slice preparations of rat medulla oblongata. 2. Noradrenaline (NA) applied by perfusion (0.01 microM to 1 mM) depolarized 55%, hyperpolarized 32% and produced a biphasic response (hyperpolarization followed by depolarization) in 9% of the d.m.v. neurones tested. 3. The NA effects persisted after complete elimination of synaptic inputs during perfusion with Ca2+‐free high‐Mg2+ solution, and therefore probably resulted from a direct action on the postsynaptic membranes. 4. The NA depolarization was blocked by prazosin and the NA hyperpolarization by yohimbine, but neither was blocked by propranolol or timolol. Phenoxybenzamine blocked both responses. The results indicate that NA depolarization is mediated by alpha 1‐adrenoceptors and hyperpolarization by alpha 2‐adrenoceptors. 5. The neurones which were depolarized by NA were also hyperpolarized by NA when the alpha 1‐adrenoceptors were blocked by prazosin (all of seven neurones tested). This result suggests that most vagal motoneurones in the d.m.v. have both alpha 1‐and alpha 2‐adrenoceptors. 6. The NA depolarization was accompanied by a decrease in membrane conductance and the hyperpolarization by an increase in membrane conductance, both of which were measured under manual‐clamp conditions. 7. The reversal potentials for the NA responses were around ‐85 mV in normal Ringer solution, and shifted as predicted by the Nernst equation when the extracellular K+ concentration was changed. 8. The inhibitory postsynaptic potentials evoked by focal electrical stimulation on the slice surface of the commissural part of the nucleus of the tractus solitarius (n.t.s.), which contains an A2 catecholaminergic cell group, were abolished by yohimbine. 9. The results suggest that NA modulates vagal output by decreasing or increasing the K+ conductance of d.m.v. neurones through alpha 1‐ or alpha 2‐adrenoceptors. In addition, the A2 noradrenergic cell group within the n.t.s. may send inhibitory inputs to the d.m.v.

Electrophysiological properties and glucose responsiveness of guinea-pig ventromedial hypothalamic neurones in vitro.

The membrane properties of neurones in the guinea‐pig ventromedial hypothalamic nucleus (v.m.h.) were studied in in vitro brain slice preparations. The average resting potential was ‐62.9 +/‐ 5.4 mV (mean +/‐ S.D.), input resistance was 155 +/‐ 58 M omega, and action potential amplitude was 69.9 +/‐ 6.3 mV. Three types of neurone were identified. The type A neurones were characterized by a short membrane time constant (7.3 +/‐ 2.0 ms) and a small after‐hyperpolarization (a.h.p.) (2.0 +/‐ 1.2 mV) with a short half decay time of 67 +/‐ 55 ms after stimulation with a long outward current pulse. Type B had a long time constant (18.8 +/‐ 5.7 ms) and a large a.h.p. (6.9 +/‐ 2.4 mV) with a medium half decay time of 203 +/‐ 90 ms. Type C was characterized by a long time constant (14.3 +/‐ 2.3 ms) and a large a.h.p. (6.5 +/‐ 1.5 mV) with a long half decay time of 478 +/‐ 230 ms. The slopes of the frequency‐current (f‐I) plots of the three types were different, particularly for the first spike interval. The slopes for the type A (414 +/‐ 102 impulses s‐1 nA‐1) and type B neurones (480 +/‐ 120 impulses s‐1 nA‐1) were steeper than that for the type C neurones (178 +/‐ 41 impulses s‐1 nA‐1). This difference is probably related to the relatively long first interval observed in the type C neurones. In all type B and a few type C neurones, when the membrane potential was hyperpolarized beyond‐‐65 mV the application of orthodromic or direct stimulation generated a burst of spikes, consisting of a low‐threshold response (l.t.r.) of low amplitude and superimposed high‐frequency spikes. At the original resting potential, outward current pulses produced a train of low‐frequency spikes. In type C neurones maintained in a depolarized state (about ‐50 mV), inward current pulses produced a specific delay of the return to the original membrane potential. This delayed return was thought to be generated by activation of a transient K+ (IA) conductance. Stimulation at the lateral edge of the v.m.h. produced excitatory post‐synaptic potentials (e.p.s.p.s) in type A neurones, e.p.s.p.s with l.t.r. in type B neurones and e.p.s.p.‐inhibitory post‐synaptic potential sequences in type C neurones. About 20% of v.m.h. neurones, particularly the type C cells, were depolarized by glucose application with an associated increase in the input membrane resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Behavioral significance of monkey hypothalamic glucose-sensitive neurons

Feeding-related neuronal activity of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons was investigated in behaving monkeys. The behavioral paradigm was a high fixed ratio of bar pressing for food reward signaled by light and tone cues. Twenty-seven percent of the neurons tested were glucose-sensitive. The population of neurons which changed in firing rate during the feeding task was higher among glucose-sensitive cells than among glucose-insensitive cells. The activity of many glucose-sensitive neurons decreased during the bar pressing and reward periods. A small population of glucose-sensitive neurons responded to cue stimuli. The results suggest that glucose-sensitive neurons are mainly involved in the drive and/or reward mechanism of feeding behavior, and that these cells may have specific roles in neural control of hunger-motivated food acquisition.

Moebius syndrome with central hypoventilation and brainstem calcification: a case report

Moebius syndrome (MS) is described in an infant with central hypoventilation and brainstem calcification. The patient had limb defects and bilateral paralysis of the 6th, 7th, 9th, 10th, and 12th cranial nerves. Mechanical ventilation was continued from birth because of shallow spontaneous respiration. Computed tomography revealed brainstem atrophy and four small calcifications restricted to the dorsal portion of the pons and medulla. Prenatal brainstem injury such as ischaemia may have caused MS and central hypoventilation.

Patent ductus venosus associated with a hyperintense globus pallidum on T1-weighted magnetic resonance imaging and pulmonary hypertension

AbstractWe report the case of a 13-year-old Japanese boy with a patent ductus venosus. He experienced mild disorientation and hallucination at age 8 years. Hyperammonaemia was discovered at age 12 years. Brain MRI demonstrated multiple intracranial hyperintense lesions, mainly in the globus pallidum, which suggested portosystemic encephalopathy. Patent ductus venosus was demonstrated by abdominal ultrasonography and angiography. Cardiopulmonary investigation revealed pulmonary hypertension. An intracranial hyperintense lesion observed on T1-weighted MRI may be an initial clue for discovering a patent ductus venosus in asymptomatic patients.ConclusionWhen patent ductus venosus is disclosed, pulmonary hypertension should be sought, as in cases with other portosystemic shunts.

Abnormal Behavioral Patterns in the Human Fetus at Term: Correlation with Lesion Sites in the Central Nervous System after Birth

We describe three fetuses at term that demonstrated abnormal behavioral patterns in utero when observed using real-time ultrasound. The abnormal patterns turned out to have neurologic correlations after birth. In case 1, despite a normal breathing pattern, no movement in any of the four extremities was observed, thus suggesting the existence of a spinal cord lesion at the rostral end, located at C4 or C5. In case 2 a lack of breathing movement was noted repeatedly, together with the abnormal finding that alternation of periods of rapid eye movement (REM) sleep with those of non-rapid eye movement (NREM) sleep was not present. These findings implied a lesion involving the pons and/or medulla oblongata. In case 3 movement of the four extremities, breathing movement, and alternating periods of REM sleep and NREM sleep were found to be within the normal range. The concurrence of regular mouthing and the NREM sleep period was not observed, however, suggesting impairment in the brain function responsible for NREM sleep located from the pons through the thalamocortical connection to the cerebral hemisphere. (J Child Neurol 1993;8:19-26).

Hypothalamic neuronal activity responses to 3-hydroxybutyric acid, an endogenous organic acid

To elucidate the anorectic action of the endogenous organic acid, 3-hydroxybutyric acid (3-HBA), its effects on neurons in both the rat ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic area (LHA) were examined. Iontophoretic application of 3-HBA significantly facilitated the firing rate of VMH neurons, whereas facilitation and inhibition were observed in the LHA. These responses were specific to the glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA. Intracellular recordings from brain slice preparations revealed that 3-HBA depolarized the cell membrane of the VMH neuron with an associated increase of membrane input resistance. This was similar to the effect of glucose on glucoreceptor neurons in the VMH. These results suggest that 3-HBA may modulate hypothalamic chemosensitive neuron activity as well as function as an endogenous satiety factor.

Drug interactions of zonisamide with phenytoin and sodium valproate: serum concentrations and protein binding.

The influence of co-medication with zonisamide (ZNS) on the serum concentration and protein binding of phenytoin (PHT) and sodium valproate (VPA) was studied in 21 pediatric patients. No significant correlation between the daily ZNS dose, and total serum concentrations, free concentrations or free fractions (FF) of PHT or VPA was observed. The patient study showed that changes in the FF of PHT and VPA were correlated more closely with the serum protein and bilirubin levels than changes in the ZNS dosage. An in vitro study revealed that the addition of ZNS caused decreases in the FF of PHT and VPA. However, these decreases were within the range of measurement error and were negligible. In conclusion, no significant effect of ZNS on the serum concentration or protein binding of PHT or VPA was demonstrated.

Surgical management of intractable epilepsy associated with cerebral neurocytomay

Abstract Neuronal neoplasms of the CNS constitute a rarely encountered group of tumors. This report concerns the surgical management of seizures encountered in four cases (ranging from 2 to 10 years-of-age at onset; consisting of two males and two females) of a recently recognized morphologically unique tumor, called ‘cerebral neurocytoma’. All patients were associated solely with intractable complex partial seizures. The tumor involved the temporal lobe in two cases, and the frontal in two. Magnetoencephalography (MEG) clearly demonstrated an accumulation of equivalent current dipoles originating from the interictal spikes on the cortex around the tumor. On intra-operative electrocorticography (ECoG), the epileptogenic zone was topographically distinct from the region of the tumor. No definite ECoG activities were observed at the tumor site, although this tumor did consist of small mature neuronal cells. Either a complete or a subtotal resection of the tumor and the epileptogenic cortex was performed and, post-operatively, universal freedom from seizures was demonstrted in all patients. A histological examination of the epileptogenic cortex revealed the presence of minute cortical dysplasia or tumor involvement in the hippocampus. A resection of the epileptogenic cortex along with the tumor was thus found to improve the seizure outcome in patients with neurocytoma-associated epilepsy without inducing any identifiable neurological deficits attributable to the incremental resection. [Neurol Res 2000; 22: 449-456]