Neurosteroid effects at α4βδ GABAA receptors alter spatial learning and synaptic plasticity in CA1 hippocampus across the estrous cycle of the mouse.

Fluctuations in circulating levels of ovarian hormones have been shown to regulate cognition (Sherwin and Grigorova, 2011. Fertil. Steril.

Characterization of neurosteroid effects on hyperpolarizing current at α4β2δ GABAA receptors.

Rationale: The neurosteroid 3α,5β-THP (3α-OH-5β-pregnan-20-one, pregnanolone) is a modulator of the GABAA receptor (GABAR), with α4β2δ GABARs the most sensitive. However, the effects of 3α,5β-THP at α4β2δ are polarity-dependent: 3α,5β-THP potentiates depolarizing current, as has been widely reported, but decreases hyperpolarizing current by accelerating desensitization.

Objectives: The present study further characterized 3α,5β-THP inhibition of hyperpolarizing current at this receptor and compared effects of other related steroids at α4β2δ GABARs.

One-stage correction of aortic coarctation and severe mitral regurgitation via left posteriolateral thoracotomy in a 2-year-old child.

We successfully treated a case of a 2-year-old male with aortic coarctation coexisting with severe mitral regurgitation via left posteriolateral thoracotomy at one stage. After a mitral valve replacement under perfused ventricular fibrillation with moderate hypothermia, we repaired the aortic coarctation with coarctation resection and end-to-end anastamosis with the aid of deep hypothermic circulatory arrest and selective low-flow cerebral perfusion. The patient had an uneventful hospital course and remains well.

Two novel mutations of the LDL receptor gene associated with familial hypercholesterolemia in a Chinese family.

Background: Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C). In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives.

Ethanol effects on GABA-gated current in a model of increased alpha4betadelta GABAA receptor expression depend on time course and preexposure to low concentrations of the drug.

Several recent studies have suggested that alphabetadelta subtypes of gamma-aminobutyric acid type A (GABAA) receptors (delta-GABAR) are a target for low dose ethanol (<30 mM). However, there are also conflicting reports suggesting that only high doses of the drug (100 mM) modulate these receptors. In addition, the studies which have demonstrated a clear effect of low dose ethanol on delta-GABAR find different effective concentrations for this effect.

Neurosteroid regulation of GABA(A) receptors: Focus on the alpha4 and delta subunits.

Neurosteroids, such as the progesterone metabolite 3alpha-OH-5alpha[beta]-pregnan-20-one (THP or [allo]pregnanolone), function as potent positive modulators of the GABA(A) receptor (GABAR) when acutely administered. However, fluctuations in the circulating levels of this steroid at puberty, across endogenous ovarian cycles, during pregnancy or following chronic stress produce periods of prolonged exposure and withdrawal, where changes in GABAR subunit composition may occur as compensatory responses to sustained levels of inhibition. A number of laboratories have demonstrated that both chronic administration of THP as well as its withdrawal transiently increase expression of the alpha4 subunit of the GABAR in several areas of the central nervous system (CNS) as well as in in vitro neuronal systems.

[Multifactor analysis of postoperative mechanical ventilation supporting time in infants with congenital heart diseases].

Objective: To analyze the multiple factors affecting the postoperative mechanical ventilation supporting time in infants less than 10 kg with simple congenital heart diseases and to seize time by the forelock of extube and improve the outcome of surgical treatment.

Methods: Data of 231 infants less than 10 kg with atrial septal defect(ASD),ventricular septal defect, and combining patent ductus arteriosus were retrospectively analyzed. The multivaricate stepwise logistic regression statistics were done for the predisposing factors affecting the ventilative supporting time.

Reversal of neurosteroid effects at alpha4beta2delta GABAA receptors triggers anxiety at puberty.

Puberty is characterized by mood swings and anxiety, which are often produced by stress. Here we show that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxiety in pubertal female mice, in contrast to its anxiety-reducing effect in adults. Anxiety is regulated by GABAergic inhibition in limbic circuits.

[Surgical treatment of partial atrioventricular septal defect].

Objective: To summarize the experience of surgical treatments of partial atrioventricular septal defect in 60 patients.

Methods: From April 1999 to April 2004, 60 patients of partial atrioventricular septal defect were operated. Fifty-eight patients were performed with suture of the cleft of mitral valve and the other 2 were given mitral valve replacement; For closure of primum ASD, 53 patients with pericardial patches and 7 with Dacron patches.

Short-term steroid treatment increases delta GABAA receptor subunit expression in rat CA1 hippocampus: pharmacological and behavioral effects.

In this study, 48 h administration of 3alpha-OH-5beta-pregnan-20-one (3alpha,5beta-THP) or 17beta-estradiol (E2)+progesterone (P) to female rats increased expression of the delta subunit of the GABA(A) receptor (GABAR) in CA1 hippocampus. Coexpression of alpha4 and delta subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7- tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 microM lanthanum (La3+). Because alpha4betadelta GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice.

[Diagnosis and surgical treatment of 102 cases of ventricular septal defect with patent ductus arteriosus].

Objective: To summarize the experience of diagnosis and surgical treatment of ventricular septal defect with patent ductus arteriosus.

Methods: We retrospectively analyzed the clinical data of 102 cases of ventricular septal defect combined with patent ductus arteriosus who underwent surgical treatment. Preoperative ultrasonic cardiogram (UCG) showed ventricular septal defect combined with patent ductus arteriosus in 82 cases and ventricular septal defect in 20 cases.

Neurosteroid administration and withdrawal alter GABAA receptor kinetics in CA1 hippocampus of female rats.

Withdrawal from the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) following exposure of female rats to the parent compound progesterone (P) produces a syndrome characterized by behavioural excitability in association with up-regulation of the alpha4 subunit of the GABA(A) receptor (GABAR) in the hippocampus. Similar changes are seen after 48 h exposure to its stereoisomer, 3alpha,5beta-THP. Here, we further characterize the effects of P withdrawal on GABAR kinetics, using brief (1 ms) application of 5-10 mm GABA to outside-out patches from acutely isolated CA1 hippocampal pyramidal cells.

Effects of a low dose of ethanol in an animal model of premenstrual anxiety.

Low (1 mM), but not 10 mM, concentrations of ethanol selectively potentiate current gated by alpha(4)beta(2)delta subunit combinations of the gamma-aminobutyric acid type A (GABA(A)) receptor, a subtype increased in hippocampus after withdrawal from progesterone in a rodent model of premenstrual anxiety. In the current study, we tested the hypothesis that the anxiolytic effect of ethanol would exhibit a similar dose-response effect by using the acoustic startle response (ASR) and elevated plus-maze as behavioral models. To this end, adult, female rats were tested (1) 24 h after removal of a progesterone-filled capsule implanted subcutaneously for 21 days (progesterone withdrawal) or (2) on the day of diestrus, a low hormone state.

Ethanol administration rapidly reverses alpha4 GABAA receptor subunit upregulation following steroid exposure.

Both short-term (48 h) exposure to the neuroactive steroid 3alpha,5alpha[beta]-THP and its withdrawal increase expression of the benzodiazepine (BDZ)-insensitive GABAA receptor (GABAR) alpha4 subunit in hippocampus. This increase in alpha4 subunit expression was associated with a relative insensitivity of CA1 hippocampal pyramidal cells to modulation of GABA-gated current by the BDZ lorazepam (LZM), assessed using whole cell patch clamp techniques. Chronic ethanol is also known to regulate expression of the alpha4 subunit.

Hormonally regulated alpha(4)beta(2)delta GABA(A) receptors are a target for alcohol.

Here we report that low concentrations of alcohol (1-3 mM) increased Cl(-) currents gated by a recombinant GABA(A) receptor, alpha(4)beta(2)delta, by 40-50% in Xenopus laevis oocytes. We also found greater hippocampal expression of receptors containing alpha(4) and delta subunits, using a rat model of premenstrual syndrome (PMS) in which 1-3 mM alcohol preferentially enhanced GABA-gated currents, and low doses of alcohol attenuated anxiety and behavioral reactivity. The alcohol sensitivity of delta-containing receptors may underlie the reinforcing effects of alcohol during PMS, when eye saccade responses to low doses of alcohol are increased.