Amygdalar catecholaminergic input to septal nuclei, relation to clomipramine actions on lateral septal neurons in the rat.

Antidepressants exert mixed actions on serotonergic and catecholaminergic systems. However, it is unknown whether a catecholaminergic blockade impinge on the actions of a tricyclic with serotonergic agonist properties (clomipramine) in limbic structures. The aim of the present study is to explore the effects of a catecholaminergic lesion in the basolateral amygdala on the firing rate of lateral septal, and hippocampal neurons in rats treated with clomipramine. An amygdaline lesion with 6-OHDA resembled the actions of clomipramine on the firing rate in lateral septal neurons, i.e. an increased rate of firing. However, the lesion blocked further effects of clomipramine on septal firing. Clomipramine decreased the firing rate in hippocampal neurons; however, neither the 6-OHDA lesion nor the added treatment with clomipramine modified the firing rate. It is concluded that an intact catecholaminergic amygdaloid input to lateral septal nuclei is necessary for clomipramine actions; however, the initial action of the tricyclic may involve a catecholaminergic blockade.     

Aminergic control of neuronal firing rate in thalamic motor nuclei of the rat

The effects induced on neuronal firing by microiontophoretic application of the biological amines noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were studied "in vivo" in ventral-anterior (VA) and ventrolateral (VL) thalamic motor nuclei of anaesthetized rats. In both nuclei the amines had a mostly depressive action on neuronal firing rate, the percentage of units responsive to NA application (88%) being higher than to 5-HT (72%). Short-lasting (less than 2 min) and long lasting (up to 20 min) inhibitory responses were recorded, the former mostly evoked by NA and the latter by 5-HT ejection. In some cases 5-HT application had no effect on the firing rate but modified the firing pattern. NA-evoked responses were significantly more intense in VL than in VA neurons. Short-lasting inhibitory responses similar to NA-induced effects were evoked by the alpha2 adrenergic receptor agonist clonidine and to a lesser extent by the beta adrenergic receptor agonist isoproterenol. Inhibitory responses to 5-HT were partially mimicked by application of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and of the 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine (ALPHA-MET-5-HT). The latter evoked excitatory responses in some cases. Both 5-HT agonists were more effective on VA than on VL neurons. The effects evoked by agonists were at least partially blocked by respective antagonists. These results suggest that although both 5-HT and NA depress neuronal firing rate, their effects differ in time course and in the amount of inhibition; besides aminergic modulation is differently exerted on VA and VL.     

The population firing rate in the presence of GABAergic tonic inhibition in single neurons and application to general anaesthesia

Tonic inhibition has been found experimentally in single neurons and affects the activity of neural populations. This kind of inhibition is supposed to set the background or resting level of neural activity and plays a role in the brains arousal system, e.g. during general anaesthesia. The work shows how to involve tonic inhibition in population rate-coding models by deriving a novel transfer function. The analytical and numerical study of the novel transfer function reveals the impact of tonic inhibition on the population firing rate. Finally, a first application to a recent neural field model for general anaesthesia discusses the origin of the loss of consciousness during anaesthesia.     

Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions.

In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated. Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei. However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus. Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons. From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist.     

Major ATPases on clofibrate-induced rat liver peroxisomes are not associated with 70 kDa peroxisomal membrane protein (PMP70).

We previously reported that novel Mg(2+)-ATPases were induced in rat liver peroxisomes by clofibrate administration and that these activities consisted of at least two types of enzymes, N-ethylmaleimide (NEM)-sensitive and -resistant. Here we present evidence that neither of these major peroxisomal ATPases is associated with the 70-kDa peroxisomal membrane protein (PMP70), because: (i) proteinase K treatment of peroxisomes resulted in inactivation of only NEM-sensitive ATPase, whereas disappeared PMP70 completely; (ii) NEM-sensitive ATPase activity was barely immunoprecipitated with anti-PMP70 IgG; (iii) the solubilized ATPases behaved differently from PMP70 on native PAGE; and finally (iv), the major peroxisomal ATPases were separated from PMP70 on gel filtration chromatography.     

Intracerebroventricular and septal injections of arginine vasopressin are not antipyretic in the rabbit

Arginine vasopressin (AVP) has been reported to have an antipyretic effect in the ewe and guinea pig near term. Perfusions with AVP of sites in the septal region also reduced fever in non-pregnant sheep. In the present experiments adult rabbits with third cerebral ventricular or septal cannulas were restrained in a 23°C environment, and rectal temperature was recorded every 10 min. Fever induced by IV administration of leukocytic pyrogen was not reduced by AVP (25–100 ng) given intraventricularly 20 min later. Doses of 1–5 μg AVP injected into the septum likewise were not antipyretic but actually caused an increase in fever. This augmentation of the febrile response is consistent with results of previous studies in this laboratory in which AVP increased hyperthermia in a hot environment and enhanced hyperthermic responses to PGE₂. The data from these experiments provide no evidence that central AVP is an endogenous antipyretic in rabbits; rather, it may be that central AVP augments fever in this species.     

Cation-dependent solubilization of rat thymocyte chromatin is closely related to decondensation of the nuclei

The cation-dependent solubilization of rat thymocyte chromatin has been compared with decondensation of the nuclei as a function of sodium phosphate-mediated changes in the concentration of Mg2+ and Na+. After digestion of the nuclei with DNase I or Micrococcus nuclease for a time just sufficient to permit extraction of a maximal amount of chromatin (minimum digestion), solubilization of most of the chromatin was found to occur with the same cation dependency as decondensation of untreated nuclei, while further digestion changed the ionic requirements for solubilization. The cation-dependency of the chromatin solubility and of the nuclear decondensation also exhibited the same variations with temperature. The chromatin in the nuclei became up to 4-times more sensitive to DNase I by decondensation, which also induced a shift in the DNase I cleavage mode from a 200 bp to a 100 bp repeat pattern. In contrast, the sensitivity to Micrococcus nuclease appeared to be nearly unchanged. These results suggest that solubilization of chromatin prepared by a mild endonuclease treatment occurs as a direct consequence of structural changes in the chromatin which take place during decondensation of the nuclei.     

Evidence for vasoactive intestinal polypeptide (VIP) altering the firing rate of preoptic,septal and midbrain central gray neurons

The effect of the iontophoretic application of vasoactive intestinal polypeptide (VIP) on the extracellular electrical activity (neuronal firing rate) of 91 neurons localized in the preoptic (PO), septal (S) region and midbrain central gray (MCG) was studied in urethane-anesthetized female rats. When applied in minute quantities, VIP induced both excitatory ($\text{N = 14}$) and inhibitory ($\text{N = 8}$) changes in the membrane excitability of PO and S neurons (total $\text{N = 58}$), while only inhibitory ($\text{N = 9}$) changes were observed in the MCG neurons (total $\text{N = 33}$; thus 24 MCG neurons were found to be unresponsive to VIP). The latency and duration of the VIP-induced response was, for the most part, characterized by a rapid onset and persisted for the duration of the ejecting pulse. However, five out of the 58 PO and S neurons and one out of the 33 MCG neurons did show responses that were longer and more variable in latency and duration. Of 26 PO neurons recorded and tested with VIP, only five neurons were determined to be antidromically identified (AI) as having their axons in the median eminence. The application of VIP increased the neuronal firing rate in two AI PO neurons, decreased the activity in one, and was ineffective in altering the activity in two other AI PO neurons. The VIP-induced changes in the neuronal firing rate appear to be specific and reproducible, and not related to the ejecting current nor pH of the solution. The results suggest that VIP, a gastrointestinal hormone that is also localized in the brain, can alter the neuronal firing rate of hypothalamic and midbrain neurons, thus providing additional evidence for its possible influence on brain and neuroendocrine function.     

Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones

We examined a possible mechanistic interaction between leptin and thyroid hormones in rats with hypothyroidism induced by thyroidectomy (TX) and propylthiouracil administration. In study 1, the TX rats were treated by vehicle (V, n = 9) or by recombinant murine leptin (L, 0.3 mg. kg(-1). day(-1), n = 9) or were pair-fed (PF, n = 9) against L. In study 2, the TX rats were all given 3, 3'5'-triiodo-L-thyronine (T(3)) replacement (T, 5 microg. kg(-1). day(-1)) to correct hypothyroidism. They were then subdivided into three groups, namely, vehicle (T+V, n = 9), leptin (T+L, n = 10), and pair-feeding (T+PF, n = 9), similar to study 1 except for T(3) (T). Reduced food consumption and weight gain in the TX rats were reversed by T(3) replacement. Leptin suppressed food intake in the TX rats regardless of T(3) replacement. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were reduced in TX rats (P < 0.05 vs. normal) but were normalized by either T(3) or leptin treatment. T+L additively increased VO(2) and VCO(2) (P < 0.05 vs. TX, T(3), and L). The respiratory exchange ratio was unaltered in TX rats, with and without T(3), but was significantly reduced by L or T+L treatments. These results indicate that the metabolic actions of leptin are not dependent on a normal thyroid status and that the effects of leptin and T(3) on oxidative metabolism are additive.     

Concepts related to salt resistant estradiol receptors in rat uterine nuclei: nuclear matrix

When ³H-estradiol (0.1 μg) is injected into immature female rats, virtually all of the label that is recovered with uterine nuclei can be solubilized by 0.6 M KCl. Salt resistant uterine nuclear estrogen binding sites do not become labeled within one hour after the injection of ³H-estradiol, but these sites do exist and can be revealed when isolated nuclei are subjected to an $\text{in vitro}$ estradiol exchange assay. These saturable, high affinity salt resistant sites appear to be associated with the uterine nuclear matrix, a residual structure of the nucleus.     

Presenilin-1 polymorphisms are not relevant in susceptibility to ventricular septal defect: a case-control study

Although many studies have demonstrated that presenilin-1 plays a vital role in cardiovascular system development, no data are available concerning association of polymorphisms of presenilin-1 with ventricular septal defect (VSD) in the Chinese population. The aim of this study was to evaluate the association between two single-nucleotide polymorphisms (rs1800844 and rs177415) of presenilin-1 and VSD. A total of 151 isolated VSD patients and 296 controls were included in the study. The genotype of the polymorphisms was determined by polymerase chain reaction-restriction fragment length polymorphism. Our study showed no statistically significant differences in genotype and allele frequencies between VSD and controls with any of the presenilin-1 genetic variants. These data may provide evidence that the presenilin-1 gene is not a genetic marker for VSD susceptibility in the Han Chinese population.     

Methylgroups of ribosomal protein L11 are not related to the synthesis of ppGpp

Summary Ribosomes carrying either a normally methylated or an undermethylated L11, respectively, were tested with respect to the stringency reaction in the presence of crude stringent factor. Systems with either kind of ribosomes synthesize ppGpp with the same efficiency. The ppGpp synthesis in presence of ribosomes with undermethylated L11 depends also on stringent factor, mRNA and deacylated tRNA whereas aminoacyl-tRNA and peptidyl-analogous tRNA show no effect. Thus, the absence of methylation in L11 does not influence the stringency reaction.     

Hepatic-dependent and -independent insulin actions are impaired in the obese Zucker rat model

Objective: Whole‐body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N‐monomethyl‐l ‐arginine (l ‐NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic‐dependent pathway is diminished in OZR, resulting in IR. Research Methods and Procedures: Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post‐atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, l ‐NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic‐dependent IS was assessed by subtracting the response after atropine or l ‐NMMA from the basal response. Results: In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 ± 14.2; LZR, 289.2 ± 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 ± 8.0%; LZR, 40.1 ± 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 ± 1.6; LZR, 287.4 ± 22.7 mg glucose/kg bw; p < 0.001). l ‐NMMA induced IS inhibition in both groups (OZR, 48.3 ± 6.6%; LZR, 46.4 ± 4.1%), similar to that after atropine. Discussion: We show that the IR in OZR is due to similar impairment of both hepatic‐dependent and ‐independent components of insulin action, suggesting the existence of a defect common to both pathways.     

Mechanistic origin of the sigmoidal rate behaviour of rat liver hexokinase D (''glucokinase'').

Two recent proposals to account for the kinetic co-operativity of hexokinase D ('glucokinase') from rat liver are examined. A model in which the deviations from Michaelis-Menten kinetics result from a random order of binding of the substrates [Pettersson (1986) Biochem. J. 233, 347-350] accounts satisfactorily for the behaviour as a function of glucose concentrations, but it also predicts observable substrate inhibition by MgATP, which is in fact not observed. An alternative proposal in which the deviations arise from recycling of an enzyme-MgADP complex [Pettersson (1986) Eur. J. Biochem. 154, 167-170] also accounts satisfactorily for some of the data, but the required enzyme-MgADP complex could not be detected in isotope-exchange measurements. Thus the mnemonical mechanism proposed originally [Storer & Cornish-Bowden (1977) Biochem. J. 165, 61-69], which explains the deviations in terms of a relatively slow interconversion between two forms of free enzyme, remains the most parsimonious explanation of the behavior of hexokinase D.     

Measurement of 5HT turnover rate in discrete nuclei of rat brain

Five non-isotopic methods of measuring serotonin turnover rate in vivo were compared in discrete nuclei of rat brain. The concentration of serotonin or 5-hydroxyindoleacetic acid was measured by high pressure liquid chromatography in the raphe nuclei, caudate nucleus and hippocampus of rats at various times after the injection of pargyline, probenecid, RO 4/4602 or α-propyldopacetamide. The turnover rate is more rapid in the cell bodies than in axon terminals.     

Pressure (< or=4 ATA) increases membrane conductance and firing rate in the rat solitary complex.

Neuronal sensitivity to pressure, barosensitivity, is illustrated by high-pressure nervous syndrome, which manifests as increased central nervous system excitability when heliox or trimix is breathed at >15 atmospheres absolute (ATA). We have tested the hypothesis that smaller levels of pressure (相似文献