Agrin regulates growth cone turning of Xenopus spinal motoneurons.

The pivotal role of agrin in inducing postsynaptic specializations at neuromuscular junctions has been well characterized. Increasing evidence suggests that agrin is also involved in neuronal development. In this study, we found that agrin inhibited neurite extension and, more importantly, a gradient of agrin induced repulsive growth-cone turning in cultured Xenopus spinal neurons.

Ca2+-dependent regulation of rho GTPases triggers turning of nerve growth cones.

Cytoplasmic Ca2+ elevation and changes in Rho GTPase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. Here we show that direct elevation of cytoplasmic Ca2+ by extracellular application of a low concentration of ryanodine, which activated Ca2+ release from intracellular stores, upregulated Cdc42/Rac, but downregulated RhoA, in cultured cerebellar granule cells and human embryonic kidney 293T cells. Chemoattractive turning of the growth cone triggered by a gradient of ryanodine was blocked by overexpression of mutant forms of Cdc42 but not of RhoA in Xenopus spinal cord neurons.

Life-threatening hypokalemia in an asthmatic patient treated with high-dose hydrocortisone.

Although modest hypokalemia is frequently observed in asthmatic patients being treated with bronchodilators, profound hypokalemia and metabolic alkalosis are rarely reported in patients receiving high-dose hydrocortisone (HC). We describe a 66-year-old man who complained of generalized muscle weakness, shallow respiration, and palpitations after receiving high-dose intravenous HC (total dose, 2400 mg over 4 days) to treat a severe asthma attack. During this therapy, there was a weight gain of 1.

Calcium signaling in chemorepellant Slit2-dependent regulation of neuronal migration.

Migration of neuronal precursor cells in the developing brain is guided by extracellular cues, but intracellular signaling processes underlying the guidance of neuronal migration are largely unknown. By examining the migration of cerebellar granule neurons along the surface of cocultured astroglial cells, we found that an extracellular gradient of Slit2, a chemorepellant for neuronal migration in vivo, caused a reversal in the direction of migration without affecting the migration speed. A Slit2 gradient elevated the intracellular concentration of Ca2+, probably due to calcium release from the internal store, led to a reversal of the preexisting asymmetric intracellular Ca2+ distribution in the soma of migrating neurons, and this reversal was closely related with its action of reversing the migrating direction.

Hepatoprotective and antioxidant effects of Bupleurum kaoi Liu (Chao et Chuang) extract and its fractions fractionated using supercritical CO(2) on CCl(4)-induced liver damage.

Fractionation with supercritical CO(2) is employed to divide ethanolic extract (E) of B. kaoi into four fractions (R, F1, F2 and F3). To assess the selectivity of the fractionation, extracts of the four fractions were characterized in terms of the hepatoprotective capacity and activity of antioxidant enzymes to against CCl(4)-induced damage.

Bidirectional modification of presynaptic neuronal excitability accompanying spike timing-dependent synaptic plasticity.

Correlated pre- and postsynaptic activity that induces long-term potentiation is known to induce a persistent enhancement of the intrinsic excitability of the presynaptic neuron. Here we report that, associated with the induction of long-term depression in hippocampal cultures and in somatosensory cortical slices, there is also a persistent reduction in the excitability of the presynaptic neuron. This reduction requires postsynaptic Ca(2+) elevation and presynaptic PKA- and PKC-dependent modification of slow-inactivating K(+) channels.

ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression.

Extracellular ATP released from axons is known to assist activity-dependent signaling between neurons and Schwann cells in the peripheral nervous system. Here we report that ATP released from astrocytes as a result of neuronal activity can also modulate central synaptic transmission. In cultures of hippocampal neurons, endogenously released ATP tonically suppresses glutamatergic synapses via presynaptic P2Y receptors, an effect that depends on the presence of cocultured astrocytes.

GDNF acutely potentiates Ca2+ channels and excitatory synaptic transmission in midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) is best known for its long-term survival effect on dopaminergic neurons in the ventral midbrain. A recent study showed that acute application of GDNF to these neurons suppresses A-type potassium channels and potentiates neuronal excitability. Here we have characterized the acute effects of GDNF on Ca(2+) channels and synaptic transmission.

Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications.

Information processing in the neuron requires spatial summation of synaptic inputs at the dendrite. In CA1 pyramidal neurons of the hippocampus, a brief period of correlated pre- and postsynaptic activity, which induces long-term potentiation (LTP) or long-term depression (LTD), results in a persistent increase or decrease in the linearity of spatial summation, respectively. Such bidirectional modification of the summation property is specific to the modified input and reflects localized dendritic changes involving I(h) channels and NMDA receptors.

Signalling and crosstalk of Rho GTPases in mediating axon guidance.

Axon extension during development of the nervous system is guided by many factors, but the signalling mechanisms responsible for triggering this extension remain mostly unknown. Here we have examined the role of Rho family small guanosine triphosphatases (GTPases) in mediating axon guidance by diffusible factors. Expression of either dominant-negative or constitutively active Cdc42 in cultured Xenopus laevis spinal neurons, at a concentration that does not substantially affect filopodial formation and neurite extension, abolishes the chemoattractive growth cone turning induced by a gradient of brain-derived neurotrophic factor that can activate Cdc42 and Rac in cultured neurons.

Nerve growth cone guidance mediated by G protein-coupled receptors.

Growing axons navigate by responding to chemical guidance cues. Here we report that growth cones of rat cerebellar axons in culture turned away from a gradient of SDF-1, a chemokine that attracts migrating leukocytes and cerebellar granule cells via a G protein-coupled receptor (GPCR). Similarly, Xenopus spinal growth cones turned away from a gradient of baclofen, an agonist of the GABA(B) receptor.

Responses of the pyramidal tract to stimulation of the baboon's motor cortex.

1. The arm area of the baboon's precentral motor cortex was stimulated by brief surface-anodal pulses, and the discharge of the corticospinal tract (the ;pyramidal tract waves') was recorded by an electrode resting on the dorsolateral surface of the cervical spinal cord.2.