[A 3D cell network which brings out relief in the pituitary gland].
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Animals↗
Biomedical subjects
Xavier Bonnefont
Publications and source records attributed to Xavier Bonnefont.
Revealing the large-scale network organization of growth hormone-secreting cells.
Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues.
Animals↗
Altered food-anticipatory activity rhythm in Cryptochrome-deficient mice.
In nocturnal rodents, restricted feeding to daytime (RF) causes feeding-associated diurnal locomotor activity that persists for the next 1-2 days when food is withheld. Along with this anticipatory behavior, the expression pattern of clock genes such as mPer1 and mPer2 changes from a nocturnal to diurnal pattern in the liver and cerebral cortex but not in the suprachiasmatic nucleus (SCN). Whether the molecular clockwork, in which mCry1 and mCry2 genes are essential components, is involved in food-anticipatory circadian rhythms is unknown. In this study, we investigated the impact of the absence of mCRY products upon the locomotion pattern induced by RF. RF caused an increase in daytime activity that lasted even for 2 days after food was withheld, in wild-type and mCry1-/-mCry2-/- mice. However, RF-induced activity was less stable and appeared more gradually in mutant mice. Similar results were obtained with mice housed under constant darkness or with SCN-lesioned wild-type and mutant mice. Our data reveal that mCry proteins are basically dispensable for food-entrainable oscillation. However, it is also important to note that mCry deficiency affects the stability and development of RF-induced anticipatory locomotor activity.
Animals↗
Acute exposure to GSM 900-MHz electromagnetic fields induces glial reactivity and biochemical modifications in the rat brain.
The worldwide proliferation of mobile phones raises the question of the effects of 900-MHz electromagnetic fields (EMF) on the brain. Using a head-only exposure device in the rat, we showed that a 15-min exposure to 900-MHz pulsed microwaves at a high brain-averaged power of 6 W/kg induced a strong glial reaction in the brain. This effect, which suggests neuronal damage, was particularly pronounced in the striatum. Moreover, we observed significant and immediate effects on the Kd and Bmax values of N-methyl-D-aspartate (NMDA) and GABA(A) receptors as well as on dopamine transporters. Decrease of the amount of NMDA receptors at the postsynaptic membrane is also reported. Although we showed that the rat general locomotor behavior was not significantly altered on the short term, our results provide the first evidence for rapid cellular and molecular alterations in the rat brain after an acute exposure to high power GSM (Global System for Mobile communication) 900-MHz microwaves.
Animals↗
Electrical activity in endocrine pituitary cells in situ: a support for a multiple-function coding.
The anterior pituitary is an endocrine gland that controls basic body functions. Pituitary cell functioning depends on membrane excitability, which induces cytosolic calcium rises. Here, we reported the first identification of small-amplitude voltage fluctuations that controlled spike firing in endocrine cells recorded in situ. Three patterns of voltage fluctuations were distinguishable by their durations (1-100 s). These patterns could be ordered on top of each other, namely in response to secretagogues. Thus, pituitary endocrine cells express in situ a cell code in which small-amplitude voltage fluctuations lead to a multimodal arrangement of spike firing, which may finely tune calcium-dependent functions.
Action Potentials↗
Light signalling in cryptochrome-deficient mice.
The mammalian master clock driving circadian rhythmicity in physiology, metabolism, and behaviour resides within the suprachiasmatic nuclei (SCN) of the anterior hypothalamus and is composed of intertwined negative and positive autoregulatory transcription-translation feedback loops. The Cryptochrome 1 and 2 gene products act in the negative feedback loop and are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel running behaviour and absence of cyclic clock gene expression in mCry1/mCry2 double mutant mice in constant darkness. Recently, we have measured real-time multi-unit electrode activity recordings in hypothalamic slices from mCry-deficient mice kept in constant darkness and observed a complete lack of circadian oscillations in firing patterns. This proves that CRY proteins, and thus an intact circadian clock, are prerequisite for circadian rhythmicity in membrane excitability in SCN neurons. Strikingly, when mCry-deficient mice are housed in normal light-dark cycles, a single non-circadian peak in neuronal activity can be detected in SCN slices prepared two hours after the beginning of the day. This light-induced increase in electric activity of the SCN suggests that deletion of the mCry genes converts the core oscillator in an hour-glass-like timekeeper and may explain why in normal day-night cycles mCry-deficient mice show apparently normal behaviour.
Animals↗
Cryptochrome-deficient mice lack circadian electrical activity in the suprachiasmatic nuclei.
The mammalian master clock driving circadian rhythmicity in physiology and behavior resides within the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Circadian rhythms are generated by a set of clock genes via intertwined negative and positive autoregulatory transcription-translation feedback loops. The Cryptochrome 1 and 2 genes are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel-running behavior and lack of rhythmic clock gene expression in mCry1/mCry2 double-mutant mice in constant darkness. In the present study, using real-time multiunit electrode activity recordings in hypothalamic slices, we show that SCN neurons from mCry-deficient mice kept in constant darkness lack circadian oscillations in firing patterns. This proves that cryptochromes, and thus an intact circadian clockwork, are prerequisites for circadian electrical activity in SCN neurons. Interestingly, when mCry-deficient mice were kept in normal light-dark conditions and SCN slices were prepared 2 hr after the beginning of the day, a single noncircadian peak in neuronal activity was detected. This light-induced rise in electrical activity of the SCN may explain why mCry-deficient mice lack the arrhythmic short bouts of wheel-running activity and instead show apparently normal behavior in normal day-night cycles.
Action Potentials↗