Developmental exposure to ethanol increases the neuronal vulnerability to oxygen-glucose deprivation in cerebellar granule cell cultures.

Prenatal alcohol exposure is associated with microencephaly, cognitive and behavioral deficits, and growth retardation. Some of the mechanisms of ethanol-induced injury, such as high level oxidative stress and overexpression of pro-apoptotic genes, can increase the sensitivity of fetal neurons towards hypoxic/ischemic stress associated with normal labor. Thus, alcohol-induced sequelae may be the cumulative result of direct ethanol toxicity and increased neuronal vulnerability towards metabolic stressors, including hypoxia.

Chronic NGF treatment induces somatic hyperexcitability in cultured dorsal root ganglion neurons of the rat.

Adult rat dorsal root ganglion (DRG) neurons cultured in the presence of 100-ng/mL NGF were reported to show spontaneous action potentials in the cell-attached recording. In this study, underlying mechanisms were examined in the whole-cell and outside-out voltage clamp recording. In 75% neurons with on-cell firing, transient inward current spikes were repetitively recorded in the voltage clamp mode at -50 mV in the whole-cell configuration (named "Isp").

Vasopressin-induced intracellular Ca²⁺ concentration responses in non-neuronal cells of the rat dorsal root ganglion.

Arginine-vasopressin (AVP) is a nonapeptide of hypothalamic origin that has been shown to exert many important cognitive and physiological functions in neurons and terminals of both the central and peripheral nervous system (CNS and PNS). Here we report for the first time that AVP induced an increase in intracellular Ca²⁺ concentration ([Ca²⁺](i)) in non-neuronal cells isolated from the rat dorsal root ganglion (DRG) and cultured in vitro. The ratiometric [Ca²⁺](i) measurements showed that AVP evoked [Ca²⁺](i) responses in the non-neuronal cells and these concentration-dependent (100 pM to 1 μM) responses increased with days in vitro in culture, reaching a maximum amplitude after 4-5 day.

Repeated PTZ treatment at 25-day intervals leads to a highly efficient accumulation of doublecortin in the dorsal hippocampus of rats.

Background: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility.

The effect of aging-associated impaired mitochondrial status on kainate-evoked hippocampal gamma oscillations.

Oscillations in hippocampal neuronal networks in the gamma frequency band have been implicated in various cognitive tasks and we showed previously that aging reduces the power of such oscillations. Here, using submerged hippocampal slices allowing simultaneous electrophysiological recordings and imaging, we studied the correlation between the kainate-evoked gamma oscillation and mitochondrial activity, as monitored by rhodamine 123. We show that the initiation of kainate-evoked gamma oscillations induces mitochondrial depolarization, indicating a metabolic response.

Segregation of calcium signalling mechanisms in magnocellular neurones and terminals.

Every cell or neuronal type utilizes its own specific organization of its Ca(2+) homeostasis depending on its specific function and its physiological needs. The magnocellular neurones, with their somata situated in the supraoptic and paraventricular nuclei of the hypothalamus and their nerve terminals populating the posterior hypophysis (neural lobe) are a typical and classical example of a neuroendocrine system, and an important experimental model for attempting to understand the characteristics of the neuronal organization of Ca(2+) homeostasis. The magnocellular neurones synthesize, in a cell specific manner, two neurohormones: arginine-vasopressin (AVP) and oxytocin (OT), which can be released, in a strict Ca(2+)-dependent manner, both at the axonal terminals, in the neural lobe, and at the somatodendritic level.

Neuroendocrine signalling: natural variations on a Ca2+ theme.

This special issue on Ca(2+) signalling in neuroendocrine cells is an opportunity to assess, through a range of first-class review articles, the complex world of endocrine signalling, a complexity that is probably best captured by calling it "diversity in unity". The unity comes from the fact that all the endocrine cells are excitable cells, able to generate action potentials and are using Ca(2+) as an essential informational molecule, coupling cell stimulation with the activation of secretion, through the exocytotic process. The 'diversity' element, illustrated by almost all the reviews, stems from the modalities employed to achieve the increase in cytosolic Ca(2+) signal, the balance between the participation of Ca(2+) entry through the plasma membrane voltage-operated Ca(2+) channels and the release of Ca(2+) from intracellular Ca(2+) stores, and the cross-talk between the Ca(2+) and cyclic AMP signalling pathways.

In vitro hippocampal gamma oscillation power as an index of in vivo CA3 gamma oscillation strength and spatial reference memory.

Neuronal synchronisation at gamma frequencies (30-100 Hz) has been implicated in cognition and memory. Gamma oscillations can be studied in various in vitro models, but their in vivo validity and their relationship with reference memory remains to be proven. By using the natural variation of wild type C57bl/6J mice, we assessed the relationships between reference memory and gamma oscillations recorded in hippocampal area CA3 in vivo and in vitro.

Calcium and normal brain ageing.

Normal brain ageing is associated with a varying degree of cognitive impairment. Although ageing is a complex, multifactorial process, and no single process could explain the ageing phenotype, a number of processes and homeostatic systems, due to their central roles in cellular physiology, have been identified as playing important roles in the process of normal ageing. In this review we revisit the basic tenets of the Ca2+ hypothesis of neuronal ageing and stress the major conceptual changes that occurred between the time of its original proposal and now, in particular in respect to the extent of neuronal loss in normal ageing.

Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent.

Normal ageing-associated spatial memory impairment has been linked to subtle changes in the hippocampal network. Here we test whether the age-dependent reduction in gamma oscillations can be explained by the changes in intrinsic properties of hippocampal interneurons. Kainate-induced gamma oscillations, but not spontaneous gamma oscillations, were reduced in slices from aged mice.

Blood-brain barrier alterations in ageing and dementia.

The current pathogenic scenarios of different types of dementia are based on a number of common mechanisms of neurodegeneration, such as accumulation of abnormal proteins (within or outside cells), mitochondrial dysfunction and oxidative stress, calcium homeostasis dysregulation, early synaptic disconnection and late apoptotic cell death. Ageing itself is associated with mild cognitive deterioration, probably due to subtle multifactorial changes resulting in a global decrease of a functional brain reserve. Increased age is a risk factor for neurodegeneration and key pathological features of dementia can also be found in aged brains.

Alterations in Ca2+-buffering in prion-null mice: association with reduced afterhyperpolarizations in CA1 hippocampal neurons.

Prion protein (PrP) is a normal component of neurons, which confers susceptibility to prion diseases. Despite its evolutionary conservation, its normal function remains controversial. PrP-deficient (Prnp(0/0)) mice have weaker afterhyperpolarizations (AHPs) in cerebellar and hippocampal neurons.

The importance of being subtle: small changes in calcium homeostasis control cognitive decline in normal aging.

Aging is a complex, multifactorial process. One of the features of normal aging of the brain is a decline in cognitive functions and much experimental attention has been devoted to understanding this process. Evidence accumulated in the last decade indicates that such functional changes are not due to gross morphological alterations, but to subtle functional modification of synaptic connectivity and intracellular signalling and metabolism.

Sphingosine 1-phosphate receptor expression profile and regulation of migration in human thyroid cancer cells.

S1P (sphingosine 1-phosphate) receptor expression and the effects of S1P on migration were studied in one papillary (NPA), two follicular (ML-1, WRO) and two anaplastic (FRO, ARO) thyroid cancer cell lines, as well as in human thyroid cells in primary culture. Additionally, the effects of S1P on proliferation, adhesion and calcium signalling were addressed in ML-1 and FRO cells. All cell types expressed multiple S1P receptors.

Normal brain ageing: models and mechanisms.

Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria-reactive oxygen species (ROS)-intracellular Ca2+.

Ca2+ regulation and gene expression in normal brain aging.

Understanding the cellular mechanisms that characterize the functional changes of the aged brain is an ongoing and formidable challenge for the neuroscience community. Evidence now links changes in Ca(2+) influx and homeostasis with perturbations induced by the aging process in the function of the main intracellular organelles involved in Ca(2+) regulation: the endoplasmic reticulum and mitochondria. New perspectives are also offered by recent gene microarray studies, illustrating the multifactorial nature of the aging process.

Hypoxia sensing and pathways of cytosolic Ca2+ increases.

Oxygen-sensing and reactivity to changes in the concentration of oxygen is a fundamental property of cellular physiology. This central role is determined, mainly, by, to the fact that oxygen represents the final acceptor of electrons, derived from the normal cellular metabolism, at the end of the mitochondrial respiratory chain. Despite significant advances in molecular characterization of various oxygen-sensitive processes, the nature of the oxygen-sensor molecules and the mechanisms that link sensors to effects remains unclear.

Mitochondrial polarisation status and [Ca2+]i signalling in rat cerebellar granule neurones aged in vitro.

Mitochondrial membrane potential is a major factor that controls, ultimately, the cellular energy supply. By use of a mitochondrial membrane potential dye (rhodamine 123, R123) and image analysis we show that during long-term (>3 weeks) culture of primary neurones (cerebellar granule neurones) there is a gradual and time-dependent depolarisation of neuronal mitochondria. This process was demonstrated by analysing the changes in the heterogeneity of the cytosolic rhodamine 123 fluorescent signal as a function of the age in culture and by measuring the amplitude of the rhodamine 123 fluorescence evoked by the addition of a mitochondrial protonophore (FCCP).

Neuronal ageing from an intraneuronal perspective: roles of endoplasmic reticulum and mitochondria.

The nature of brain ageing and the age-dependent decline in cognitive functions remains poorly understood. Physiological brain ageing is characterised by mild mental dysfunctions, whereas age-dependent neurodegeneration, as illustrated by Alzheimer disease (AD), results rapidly in severe dementia. These two states of the aged brain, the physiological and the pathological, are fundamentally different as the latter stems from significant neuronal loss, whereas the former develops without significant neuronal demise.