BDNF boosts spike fidelity in chaotic neural oscillations.

Oscillatory activity and its nonlinear dynamics are of fundamental importance for information processing in the central nervous system. Here we show that in aperiodic oscillations, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances the accuracy of action potentials in terms of spike reliability and temporal precision. Cultured hippocampal neurons displayed irregular oscillations of membrane potential in response to sinusoidal 20-Hz somatic current injection, yielding wobbly orbits in the phase space, i.

Developmental switch in axon guidance modes of hippocampal mossy fibers in vitro.

Hippocampal mossy fibers (MFs), axons of dentate granule cells, run through a narrow strip, called the stratum lucidum, and make synaptic contacts with CA3 pyramidal cells. This stereotyped pathfinding is assumed to require a tightly controlled guidance system, but the responsible mechanisms have not been proven directly. To clarify the cellular basis for the MF pathfinding, microslices of the dentate gyrus (DG) and Ammon's horn (AH) were topographically arranged in an organotypic explant coculture system.

Laboratory diagnosis of canine GM2-gangliosidosis using blood and cerebrospinal fluid.

In the present study, laboratory techniques were used to diagnose canine GM2-gangliosidosis using blood and cerebrospinal fluid (CSF) that can be collected noninvasively from living individuals. Lysosomal acid beta-hexosaminidase (Hex) was measured spectrofluorometrically using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide and 4-methylumbelliferyl 7-(6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside) as substrates. Main isoenzymes A and B of Hex in leukocytes were also analyzed using cellulose acetate membrane electrophoresis.

NF-kappa B controls cell fate specification, survival, and molecular differentiation of immunoregulatory natural T lymphocytes.

Ontogenetic, homeostatic, and functional deficiencies within immunoregulatory natural T (iNKT) lymphocytes underlie various inflammatory immune disorders including autoimmunity. Signaling events that control cell fate specification and molecular differentiation of iNKT cells are only partly understood. Here we demonstrate that these processes within iNKT cells require classical NF-kappaB signaling.

5-Fluorouracil, methotrexate, leucovorin, CDDP and epirubicin (FEPMTX): a wide-spectrum regimen of salvage chemotherapy for high-grade advanced gastric cancer.

Background/aims: Twenty-one patients with primary stage IV gastric cancer were treated with a wide-spectrum regimen, designated as FEPMTX therapy to establish an effective salvage chemotherapy.

Methodology: FEPMTX therapy consisted of 5-fluorouracil and the triple biochemical modulators in addition to epirubicin. The schedule comprised 3 days continuous administration of 5-fluorouracil (350 mg/m2/day) and; methotrexate (MTX; 35 mg/m2) on day 1, calcium leucovorin (LV; 30 mg/m2) on day 2 and 3, cisplatin (CDDP; 30 mg/m2) and epirubicin (20 mg/m2) on day 3 every 2 weeks in principle.

A murine locus on chromosome 18 controls NKT cell homeostasis and Th cell differentiation.

Th cell differentiation is a critical event in the adaptive immune response. C57BL strains develop predominant Th1 responses while BALB/c develops a predominant Th2 response. To identify quantitative trait loci controlling this variation, we performed Th1/Th2 differentiation assays of F(1) x BALB/c progeny.

Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected].

Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor beta-chain repertoire and how alpha-galactosylceramide (alpha-GalCer) analogues induce distinct functional responses have remained elusive.

Beta-amyloid prevents excitotoxicity via recruitment of glial glutamate transporters.

Amyloid beta-protein (Abeta), a putative pathogenic endotoxin involved in Alzheimer's disease, induces redistribution of glutamate transporters in astrocytes and promotes their pump activity. Because the transporters are assumed to protect neurons against excitotoxicity by removing extracellular glutamate, we hypothesized that Abeta alters the vulnerability of neurons to glutamate. Cerebrocortical neuron-astroglial co-cultures were exposed to glutamate, the concentration of which was selected so that only 20% of the neurons exhibited degeneration.

Estrogens inhibit l-glutamate uptake activity of astrocytes via membrane estrogen receptor alpha.

We investigated the effects of estrogen-related compounds including xenoestrogens [17beta-estradiol (E2), 17alpha-ethynylestradiol (EE), diethylstilbestrol (DES), p-nonylphenol (PNP), bisphenol A (BPA) and 17alpha-estradiol (17alpha)] on l-glu uptake by cultured astrocytes via glutamate-aspartate transporter (GLAST). After 24 h treatment, E2 inhibited the l-glu uptake at 1 micro m and higher concentrations. EE and DES also inhibited the l-glu uptake at 1 nm and higher concentrations.

Activity-evoked capacitative Ca2+ entry: implications in synaptic plasticity.

The Ca2+ influx controlled by intracellular Ca2+ stores, called store-operated Ca2+ entry (SOC), occurs in various eukaryotic cells, but whether CNS neurons are endowed with SOC capability and how they may operate have been contentious issues. Using Ca2+ imaging, we present evidence for the presence of SOC in cultured hippocampal pyramidal neurons. Depletion of internal Ca2+ stores by thapsigargin caused intracellular Ca2+ elevation, which was prevented by SOC channel inhibitors 2-aminoethoxydiphenyl borate (2-APB), SKF96365, and La3+.

Genetic dissection of V alpha 14J alpha 18 natural T cell number and function in autoimmune-prone mice.

Nonobese diabetic (NOD) mice, a model for type I diabetes (TID), have reduced numbers of invariant V alpha 14J alpha 18 TCR alpha-chain-positive natural T (iNKT) cells that do not release IL-4 in response to in vivo activation through their Ag receptor. The deficit in iNKT cell number and function is implicated in immune dysregulation and the etiology of TID. Therefore, we reasoned that the genetic determinant(s) that controls iNKT cell number and function might lie within Idd (insulin-dependent diabetes susceptibility locus) regions, which are known to contain TID resistance or susceptibility genes.

Mossy fiber pathfinding in multilayer organotypic cultures of rat hippocampal slices.

1. Using a novel technique of organotypic cultures, in which two hippocampal slices were cocultured in a bilayer style, we found that the mossy fibers arising from the dentate gyrus grafted onto another dentate tissue grew along the CA3 stratum lucidum of the host hippocampal slice. The same transplantation of a CA1 microslice failed to form a network with the host hippocampus.

Different Ca2+ dynamics between isolated hippocampal pyramidal cells and dentate granule cells.

The hippocampal formation contains a variety of neuronal types. The principal neurons are granule cells in the dentate gyrus and pyramidal cells in Ammon's horn. These two neuron types show distinct cell morphology and display a different vulnerability to ischemic injury or various neurotoxins.

Mossy fibre synaptic NMDA receptors trigger non-Hebbian long-term potentiation at entorhino-CA3 synapses in the rat.

Hippocampal CA3 pyramidal cells receive two independent afferents from the enthorinal cortex, i.e. a direct input via the temporoammonic pathway (TA, perforant path) and an indirect input via the mossy fibres (MF) of dentate granule cells.

Fimbrial control of bidirectional synaptic plasticity of medial perforant path-dentate transmission.

Lesions of the fimbria-fornix (FF) tract cause profound impairments of cognitive ability in animals. Our previous study showed that spatial performance correlates with long-term potentiation (LTP) of the dentate gyrus (DG), but not of the CA1 region, in rats with bilateral FF lesions, suggesting that FF lesions selectively inhibited LTP in the DG. The cortical input to the DG is anatomically and physiologically divided into two types of afferents, i.

[Multidisciplinary therapy for peritoneal dissemination using peritonectomy].

An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia.

Interleukin-1beta abrogates long-term depression of hippocampal CA1 synaptic transmission.

Although interleukin-1beta (IL-1beta) is well known to modulate synaptic transmission and plasticity of the hippocampus, no study has yet evaluated how this cytokine affects long-term depression (LTD), one of the major forms of hippocampal synaptic plasticity. Here we report that at Schaffer collateral-CA1 synapses, bath application of IL-1beta induces a long-lasting decrease in synaptic strength in intact slices, but not in disinhibited slices in the presence of bicuculline, a gamma-aminobutyric acid receptor antagonist. The IL-1beta-induced synaptic depression efficiently foreclosed the subsequent induction of LTD in response to a 1-Hz tetanus and, conversely, it was also prevented by preexisting LTD.

Effects of 17beta-estradiol and xenoestrogens on the neuronal survival in an organotypic hippocampal culture.

Xenoestrogens are man-made compounds that mimic the actions of estrogens through interactions with estrogen receptors (ERs). Although xenoestrogens have received a great deal of attention as possible causes of brain disfunctions, little information concerning the effects of xenoestrogens on the central nervous system is available. In this study, we investigated the effects of 17beta-estradiol (E(2)) and four xenoestrogens (17alpha-ethynylestradiol, diethylstilbestrol, p-nonylphenol and bisphenol A (BPA)) on the neuronal survival using organotypic hippocampal slice cultures.

Effects of isulin-like growth factor-I on maternal and fetal plasma amino acid levels in pregnant rats.

Pregnant rats were subcutaneously administered with recombinant human insulin-like growth factor-I (rhIGF-I) in doses of 0 (control), 1, 2, and 4 microg/g body weight per day from day 18 to 21 of pregnancy. On day 21 of pregnancy, maternal and fetal plasma samples were collected and those amino acid levels were measured. The ratios of fetal/maternal plasma amino acids, especially leucine, isoleucine, tryptophan, phenylalanine and tyrosine, increased in 2 microg rhIGF-I treated group.

Hippocampal long-term depression as an index of spatial working memory.

Long-term potentiation (LTP), a form of synaptic plasticity in the hippocampus, is a cellular model for the neural basis of learning and memory, but few studies have investigated the contribution of long-term depression (LTD), a counterpart of LTP. To address the possible relationship between hippocampal LTD and spatial performance, the spatial cognitive ability of a rat was assessed in a spontaneous alternation test and, thereafter, LTD in response to low-frequency burst stimulation (LFBS) was monitored in the dentate gyrus of the same rat under anaesthesia. To enhance a divergence in the ability for spatial performance, some of the animals received fimbria-fornix (FF) transection 14 days before the experiments.

Effects of epidermal growth factor on placental amino acids uptake in pregnant rats.

To evaluate the effects of epidermal growth factor (EGF) on placental amino acids uptake, transport activities for L-proline, L-leucine, and L-alanine were kinetically examined in placental microvillous vesicles(PMV) obtained from pregnant rats administered with EGF(100 and 200 microg/kg/day) from day 18 to 21 of pregnancy. The Vmax of Na(+)-dependent proline uptake remarkably increased with a dose-dependent manner of EGF, while Km did not change. In contrast, Vmax and Km values of Na(+)-dependent and -independent alanine, and Na(+)-independent leucine uptake were not affected.

Sandhoff disease in a golden retriever dog.

A golden retriever dog is described with total hexosaminidase deficiency and raised GM2-ganglioside in CSF. The animal represents a model for human Sandhoff disease.

Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms in cultured hippocampal neurons.

Brain-derived neurotrophic factor (BDNF) has been implicated in activity-dependent plasticity of neuronal function and network arrangement. To clarify how BDNF exerts its action, we evaluated the physiological, histological, and biochemical characteristics of cultured hippocampal neurons after long-term treatment with BDNF. Here we show that BDNF facilitates high K(+)-elicited release of GABA but not of glutamate and induces an increase in immunoreactive signals of glutamic acid decarboxylase, a GABA-synthesizing enzyme.

Vasopressin induces emesis in Suncus murinus.

This paper reports that vasopressin is emetogenic in the house musk shrew Suncus murinus. Either intravenous or intracerebroventricular administration of vasopressin caused vomiting within a few minutes. The ED50 of intravenous vasopressin was as high as 4.

BDNF attenuates hippocampal LTD via activation of phospholipase C: implications for a vertical shift in the frequency-response curve of synaptic plasticity.

Recent evidence shows that neurotrophins are not only involved in neuronal survival and differentiation during development but also in modulating synaptic strength in the mature brain. To understand how neurotrophins alter this synaptic modification, we have investigated the effect of brain-derived neurotrophic factor (BDNF) on long-term depression (LTD) at Schaffer collateral-CA1 synapses in rat hippocampal slices. The slices treated with BDNF for 5 min showed significantly less LTD in response to a 1-Hz tetanus compared with controls but displayed normal LTD when the afferents were tetanized at 10 Hz.