Neuroscience
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Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence. ⋯ No differences in spread of evoked activity were observed between spontaneously and non-spontaneously active LA slices, i.e. basic properties of evoked synaptic responses were similar in the two functional types of LA slices, including input-output relationship, and paired-pulse depression. These results indicate a directed propagation of synaptic signals within the human LA in spontaneously active epileptic slices. We suggest that the lack of differences in local and in systemic information processing has to be found in confined epileptiform circuits within the amygdala likely involving well-known "epileptic neurons".
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Alteration in gene expression along the pain signaling pathway is a key mechanism contributing to the genesis of neuropathic pain. Accumulating studies have shown that epigenetic regulation plays a crucial role in nociceptive process in the spinal dorsal horn. In this present study, we investigated the role of enhancer of zeste homolog-2 (EZH2), a subunit of the polycomb repressive complex 2, in the spinal dorsal horn in the genesis of neuropathic pain in rats induced by partial sciatic nerve ligation. ⋯ Intrathecal injection of the EZH2 inhibitor attenuated the development and maintenance of mechanical and thermal hyperalgesia in rats with nerve injury. Such analgesic effects were concurrently associated with the reduced levels of EZH2, H3K27TM, Iba1, GFAP, TNF-α, IL-1β, and MCP-1 in the spinal dorsal horn in rats with nerve injury. Our results highly suggest that targeting the EZH2 signaling pathway could be an effective approach for the management of neuropathic pain.
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Altered corneal reflex activity is a common feature of dry eye disease (DE). Trigeminal sensory nerves supply the ocular surface and terminate at the trigeminal interpolaris/caudalis (ViVc) transition and spinomedullary (VcC1) regions. Although both regions contribute to corneal reflexes, their role under dry eye conditions is not well defined. ⋯ Blockade of N-methyl-D-aspartate (NMDA) receptors at either region reduced HS-evoked OOemgL activity in DE and sham rats. GABAαβ3 receptor density was reduced at the ViVc transition, while NMDA receptor density was increased at both regions in DE rats. Loss of GABAergic inhibition at the ViVc transition coupled with enhanced NMDA excitatory amino acid neurotransmission at the ViVc transition and the VcC1 region likely contribute to altered corneal reflexes under dry eye conditions.
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Neuroinflammation is known to play a key role in the prognosis of functional recovery after spinal cord injury (SCI). The involvement of microglial and mast cells in early and late stages of inflammation has been receiving increasing attention. This study was aimed at determining the influence of a pro-inflammatory cytokine, the granulocyte macrophage-colony stimulating factor (GM-CSF), on microglia and mast cell activation, glial scar formation and functional recovery following SCI. ⋯ A transient decrease in pro-inflammatory cytokines after GM-CSF treatment was also observed, whereas the endogenous GM-CSF level was unchanged. While the beneficial role of GM-CSF in reducing glial scar is confirmed, our findings reveal that neuroinflammatory events mediated by microglial and mast cells as well as the alteration of IL-1β and IL-6 levels are paralleled with an improvement in tactile recovery. These mechanisms could limit the duration and intensity of homeostatic imbalance and promote the plasticity of spared tissues.
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Increases in plasma osmolality activates the paraventricular nucleus of the hypothalamus (PVN) which in turn mounts a physiological response by increasing the release of arginine vasopressin and sympathetic nerve activity to end organs such as the kidney. The PVN expresses an abundance of purinergic receptors including P2X2 receptors. In the present study, we sought to determine (1) whether P2X2-expressing PVN neurons are activated by hypertonic saline or hypertonic mannitol and (2) what effects P2X receptor blockade has on sympathetic nerve activation mediated by a hyperosmotic stimulus. ⋯ Microinjection of a P2X receptor antagonist, PPADS, within the PVN significantly attenuated sympathetic nerve activation driven by a hyperosmotic stimulus. The hyperosmotically induced increase in lumbar sympathetic nerve activity was significantly blunted after PPADS pre-treatment. Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X2 expressing PVN neurons that might facilitate increased sympathetic drive.