Neuroscience
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It was recently reported that glia cell line-derived neurotrophic factor (GDNF) facilitates presynaptic axonal growth and neurotransmitter release at neuromuscular synapses. Little is known, however, whether GDNF can also act on the postsynaptic apparatus and its underlying mechanisms. Using biochemical cold blocking of existing membrane acetylcholine receptors (AchRs) and biotinylation of newly inserted receptors we demonstrate that GDNF increases the insertion of AChRs into the surface membrane of mouse primary cultured muscle cells and that this does not require protein synthesis. ⋯ GDNF may signal through c-Ret as well as NCAM-140 pathways since both the signaling receptors are expressed in the neuromuscular junction (NMJ). These data suggest that GDNF is an autocrine regulator of NMJ to promote the insertion and stabilization of postsynaptic AchRs. In vivo, GDNF may function as a synaptotrophic modulator for both pre- and postsynaptic differentiation to strengthen the functional and structural connections between nerve and muscle, and contribute to the synaptogenesis and plasticity of neuromuscular synapses.
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Comparative Study
The hypothalamic-pituitary-adrenal and glucose responses to daily repeated immobilisation stress in rats: individual differences.
It is accepted that there are important individual differences in the vulnerability to stress-induced pathologies, most of them associated to the hypothalamic-pituitary and sympatho-medullo-adrenal axes, the two prototypical stress-responsive systems. However, there are few studies specifically aimed at characterising individual differences in the physiological response to daily repeated stress in rats. In the present work, male rats were submitted to repeated immobilisation (IMO) stress (1 h daily for 13 days) and several samples were taken at specific days and time points. ⋯ When the animals were classified in three groups on the basis of their plasma ACTH levels immediately after the first immobilisation, individual differences in the ACTH response progressively disappeared on successive exposures to the stressor, whereas those in corticosterone and glucose were more sustained. The present results suggest that there are individual differences in the physiological response to stress that tend to be reduced rather than accentuated by repeated exposure to the stressor. Nevertheless, this buffering effect of repeated stress was dependent on the particular variable studied.
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The medial preoptic area (MPOA) is important for reproductive behavior in females. However, the descending pathways mediating these responses to the spinal motor output are unknown. The MPOA does not directly innervate the spinal cord. ⋯ Injection of biotinylated dextran amine into the MPOA produced dense labeling in specific regions of the PAG and Barrington's nucleus; anterogradely labeled fibers terminated close to neurons retrogradely labeled from the spinal cord in the PAG, Barrington's nucleus, nPGi, lateral hypothalamus and paraventricular nucleus (PVN). Anterogradely labeled fibers and varicosities were also found close to neurons retrogradely labeled from the nPGi in the PAG, lateral hypothalamus and PVN. These results suggest that the major MPOA output relays in the PAG and nPGi before descending to innervate spinal circuits regulating female genital reflexes and that the MPOA plays a multifaceted role in female reproductive behavior through its modulation of PAG output systems.
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Different lines of evidence indicate that ATP and nitric oxide (NO) play key roles in mediating neuronal responses after cell damage. Purinergic and nitrergic interactions have been proposed in non neural tissues physiological functions and, in different experimental models of brain injury, both purinergic and nitrergic activations have been reported. The present study was planned to ascertain possible relations of these two systems after brain damage. ⋯ Present data demonstrate that after cerebellar lesion nitrergic and purinergic systems are activated with similar time courses in precerebellar stations. Further, time differences in the relation between nNOS expression and cell survival suggest a multifarious role of NO in mediating cell reaction to axotomy. The tight cellular co-localization and temporal co-activation of purinergic and nitrergic markers indicate possible interactions between these two systems also in the CNS.
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Comparative Study
Initiation of electrographic seizures by neuronal networks in entorhinal and perirhinal cortices in vitro.
The hippocampus is often considered to play a major role in the pathophysiology of mesial temporal lobe epilepsy. However, emerging clinical and experimental evidence suggests that parahippocampal areas may contribute to a greater extent to limbic seizure initiation, and perhaps epileptogenesis. To date, little is known about the participation of entorhinal and perirhinal networks to epileptiform synchronization. ⋯ These procedures also shortened ictal discharge duration in the entorhinal cortices, but not in the perirhinal area. Similar results could be obtained by applying Mg(2+)-free medium (n=7). These findings indicate that parahippocampal networks provide independent epileptiform synchronization sufficient to sustain limbic seizures as well as that the perirhinal cortex plays a preferential role in in vitro ictogenesis.