Neuroscience
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Different forms of electrical paroxysms in experimental animals mimic the patterns of absence seizures associated with spike-wave complexes at approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike-wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20 Hz. Both these types of electrical seizures are preferentially generated during slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker that would account for suddenly generalized spike-wave seizures as well as the idea of an exclusive role of synaptic excitation in the generation of paroxysmal depolarizing components, and we focus on three points, based on multiple intracellular and field potential recordings in vivo that are corroborated by some clinical studies: (a) the role of neocortical bursting neurons, especially fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200 Hz) in seizure initiation; (b) the cortical origin of both these types of electrical paroxysms, the synaptic propagation of seizures from one to other, local and distant, cortical sites, finally reaching the thalamus, where the synchronous cortical firing excites thalamic reticular inhibitory neurons and thus leads to steady hyperpolarization and phasic inhibitory postsynaptic potentials in a majority of thalamocortical neurons, which might explain the obliteration of signals from the external world and the unconsciousness during absence seizures; and (c) the cessation of seizures, whose cellular mechanisms have only begun to be investigated and remain an open avenue for research.
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Aquaporin-4 (AQP4) is the major water channel in the CNS. Its expression at fluid-tissue barriers (blood-brain and brain-cerebrospinal fluid barriers) throughout the brain and spinal cord suggests a role in water transport under normal and pathological conditions. Phenotype studies of transgenic mice lacking AQP4 have provided evidence for a role of AQP4 in cerebral water balance and neural signal transduction. ⋯ In contrast, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema caused by freeze-injury and brain tumor, probably due to impaired AQP4-dependent brain water clearance. AQP4-null mice also have markedly reduced acoustic brainstem response potentials and significantly increased seizure threshold in response to chemical convulsants, implicating AQP4 in modulation of neural signal transduction. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the CNS associated with altered brain water balance.
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Comparative Study
Serotonergic response to social stress and artificial social sign stimuli during paired interactions between male Anolis carolinensis.
Serotonergic activity is influenced by social status and manipulation of social signals. In the lizard Anolis carolinensis, eyespot formation, i.e. darkening of postorbital skin from green to black, appears during stressful and agonistic situations, forming first in males that become dominant. To assess the effect of eyespots on central serotonergic activity during social interaction, males were paired by weight and painted postorbitally with green or black paint. ⋯ Decreased hypothalamic serotonin was associated with increased aggressive behavior. These results, when compared with previous studies, suggest some flexibility in central serotonergic systems, which may shape dominant and subordinate rank acquisition, and appear to be influenced by the completion of social role formation. Furthermore, social status and central serotonergic activity was influenced by a visual cue, the presence or absence of postorbital eyespots on an opponent.
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Comparative Study
Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy.
Previous studies have raised the possibility that a decrease in voltage-gated K+ currents may contribute to hyperexcitability of injured dorsal root ganglion (DRG) neurons and the emergence of neuropathic pain. We examined the effects of axotomy on mRNA levels for various Kv1 family subunits and voltage-gated K+ currents in L4-L5 DRG neurons from sham-operated and sciatic nerve-transected rats. RNase protection assay revealed that Kv1.1 and Kv 1.2 mRNAs are highly abundant while Kv1.3, Kv1.4, Kv1.5 and Kv1.6 mRNAs were detected at lower levels in L4-L5 DRGs from sham and intact rats. ⋯ Axotomy decreased both types of K+ currents by 50-60% in injured DRG neurons. In addition, axotomy increased the alpha-dendrotoxin sensitivity of the delayed rectifier, but not slow A-type K+ currents in injured DRG neurons. These results suggest that Kv1.1 and Kv1.2 subunits are major components of voltage-gated K+ channels in L4-L5 DRG neurons and that the decreased expression of Kv1-family subunits significantly contributes to the reduction and altered kinetics of Kv current in axotomized neurons.
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Comparative Study
Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea.
Chronic intermittent hypoxia (CIH), as occurs in obstructive sleep apnea (SA), is associated with substantial cortico-hippocampal damage leading to impairments of neurocognitive, respiratory and cardiovascular functions. Previous studies in a rat model have shown that CIH increases brain cortical neuronal cell death. However, the molecular events leading to CIH-mediated neuronal cell death remain largely undefined. ⋯ Furthermore, exposure of mice to CIH induced caspase-3 activation and increased some cortical neuronal cell apoptosis. On the other hand, transgenic mice overexpressing Cu,Zn-superoxide dismutase exposed to CIH conditions had a lower level of steady-state ROS production and reduced neuronal apoptosis in brain cortex compared with that of normal control mice. Taken together, these findings suggest that the increased ROS production and oxidative stress propagation contribute, at least partially, to CIH-mediated cortical neuronal apoptosis and neurocognitive dysfunction.