Neuroscience
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Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the mechanisms of hyperexcitability that lead to seizures. ⋯ KCC2 IR was observed in neurons of different size, including large dysplastic neurons, but not in balloon cells or in glial cells with astrocytic morphology. Double-labeling experiments confirmed the differential cellular distribution of the two CCTs and their expression in GABA(A) receptor (alpha1 subunit)-positive dysplastic neurons. The cellular distribution of CCTs, with high expression of NKCC1 in dysplastic neurons and altered subcellular distribution of KCC2 resembles that of immature cortex and suggests a possible contribution of CCTs to the high epileptogenicity of malformations of cortical development.
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Neuropathic pain is typified by injuries to the peripheral and central nervous system and derives from such causes as cancer, diabetes, multiple sclerosis, post-herpetic neuralgia, physical trauma or surgery, and many others. Patients suffering neuropathic pain do not respond to conventional treatment with non-steroidal anti-inflammatory drugs and show a reduced sensitivity to opiates often associated with serious side effects. Recently, it has been demonstrated that botulinum neurotoxin serotype-A (BoNT/A) is able to induce analgesia in inflammatory pain conditions. ⋯ Remarkably, a single non-toxic dose of BoNT/A was sufficient to induce anti-allodynic effects, which lasted for at least 3 weeks. This result is particularly relevant since neuropathic pain is poorly treated by current drug therapies. This communication enlarges our knowledge on potentially new medical uses of BoNT/A in efforts to ameliorate human health conditions, with very important implications in the development of new pharmacotherapeutic approaches against neuropathic pain.
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The skewed amplitude distribution of spontaneous excitatory junction potentials (sEJPs) in the mouse vas deferens and other electrically-coupled smooth muscle syncytia has been attributed to electrically-attenuated depolarizations resulting from the spontaneous release of quantized packets of ATP acting on remote smooth muscle cells (SMCs). However, in the present investigation surface SMCs of the mouse isolated vas deferens were poorly electrically coupled, with input resistances (176+/-18 MOmega, range: 141-221 MOmega, n=4) similar to those of dissociated cells. Furthermore, the amplitude of evoked EJPs was more variable in surface compared with deeper SMCs (F test, F=17.4, P<0.0001). ⋯ The temporal correlation between sEJPs of widely ranging amplitude with NCTs in the impaled SMC demonstrates that all sEJPs could arise from neurotransmitter action on the impaled cell and that the skewed distribution of sEJPs can be explained by the variable effect of packets of ATP on a single SMC. The amplitude correlation of sEJPs and NCTs argues against the attenuation of electrical signal amplitude along the length of a single SMC. The skewed sEJP amplitude distribution arising from neurotransmitter release on single SMCs is consistent with a broad neurotransmitter packet size distribution at sympathetic neuroeffector junctions.
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Previous studies have demonstrated that opioid receptors in the prefrontal ventrolateral orbital cortex (VLO) are involved in anti-nociception. The aim of this current study was to examine whether opioid receptors in the VLO have effects on the hypersensitivity induced by contralateral L5 and L6 spinal nerve ligation (SNL), termed as mirror neuropathic pain (MNP) in the male rat. Morphine (1.0, 2.5, 5.0 microg) microinjected into the VLO contralateral to the SNL depressed the mechanical paw withdrawal assessed by von Frey filaments and the cold plate (4 degrees C)-induced paw lifting in a dose-dependent manner on the side without SNL. ⋯ The effects of both drugs were blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75 microg), but the effect of the DADLE was not influenced by the selective delta-receptor antagonist naltrindole (5.0 microg). Microinjection of the kappa-opioid receptor agonist spiradoline mesylate salt (U-62066) (100 microg) had no effect on the MNP. These results suggest that the VLO is involved in opioid-induced inhibition of the MNP and the effect is mediated by mu- (but not delta- and kappa-) opioid receptors.
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Recent in vitro studies have found that astrocytes exert powerful control over the number of neuronal synapses, leading us to consider why glia can exert this control and what the underlying mechanism(s) may be. To understand the potential possibility, we studied the formation of synapses and synaptic function in primary rat cortical neurons. We found that primary cultured neonatal rat cortical astrocytes modulate synaptogenesis and synaptic function through producing and secreting estradiol into culture medium. ⋯ Finally, to understand whether astrocyte-derived estradiol regulates the synaptic transmission via presynapse, the release of presynaptic vesicle from neuron was monitored by FM 4-64 assay. The results showed that when ACM or exogenic estradiol was added into neurons, the kinetics of vesicle release speed are similar to that of neuronal cultured with astrocytes, which were faster than that of just pure neuronal cultures. These observations suggest that estrogen synthesized and secreted by astrocytes can regulate synapse formation and synaptic transmission.