Neuroscience
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Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception. In the present study, we explored the interaction between the two systems by examining the mutual effects between TNF-α and the Ang II/AT1 receptor axis in dorsal root ganglion (DRG) neurons. Rat DRG neurons were treated with TNF-α in different concentrations for different lengths of time in the presence or absence of transcription inhibitor actinomycin D, TNF receptor 1 (TNFR1) inhibitor SPD304, β-catenin signaling inhibitor CCT031374, or different kinase inhibitors. ⋯ In conclusion, we demonstrate that TNF-α inhibits AT1 receptor expression at the transcription level via TNFR1 in rat DRG neurons by increasing the soluble β-catenin level through the p38 MAPK/GSK-3β pathway. In addition, Ang II appears to inhibit and induce TNF-α expression via the AT1 receptor and the AT2 receptor in DRG neurons, respectively. This is the first evidence of crosstalk between TNF-α and the Ang II/AT receptor axis in DRG neurons.
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Non-invasive brain imaging requires comprehensive interpretation of hemodynamic signals. In functional magnetic resonance imaging, blood oxygen level dependent (BOLD) signals are used to infer neural processes. This necessitates a clear understanding of how BOLD signals and neural activity are related. ⋯ During excitatory binocular interaction, we find that metabolic, spiking, and local field potential responses are correlated. However, during suppressive binocular interaction, spiking activity and local field potentials (LFP) are dissociated while only the latter is coupled with metabolic response. These results suggest that inhibitory connections may be a key factor in the dissociation between LFP and spiking activity, which may contribute substantially to the close coupling between the BOLD signal and synchronized synaptic activity in the brain.
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Migraine attacks are typically described as unilateral, throbbing pain that is usually accompanied by nausea, vomiting, and exaggerated sensitivities to light, noise and smell. The headache phase of a migraine attack is mediated by activation of the trigeminovascular pathway; a nociceptive pathway that originates in the meninges and carries pain signals through meningeal nociceptors to the spinal trigeminal nucleus and from there to the cortex through relay neurons in the thalamus. Recent studies in our lab have identified a population of trigeminovascular neurons in the posterior (Po) and lateral posterior (LP) thalamic nuclei that may be involved in the perception of whole-body allodynia (abnormal skin sensitivity) and photophobia (abnormal sensitivity to light) during migraine. ⋯ Such injections yielded retrogradely labeled neurons in the nucleus of the diagonal band of Broca, the dopaminergic cells group A11/A13, the ventromedial and ventral tuberomammillary nuclei of the hypothalamus. We also found that some of these neurons contain acetylcholine, dopamine, cholecystokinin and histamine, respectively. Accordingly, we speculate that these forebrain/hypothalamic projections to Po and LP may play a role in those migraine attacks triggered by disrupted sleep, skipping meals and emotional reactions.
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Intracerebroventricular (i.c.v.) injection of kynurenic acid (KYNA) had sedative and hypnotic effects during stress in neonatal chicks. However, its mechanism has not been clarified. KYNA is an endogenous antagonist of the α7 nicotinic acetylcholine (α7nACh) receptor and N-methyl-d-aspartate (NMDA) receptor. ⋯ In Experiment 2, the role of the NMDA receptor was investigated using the NMDA receptor antagonist (+)-MK-801, d-serine which has high affinity to a co-agonist glycine site at the NMDA receptors, NMDA as the NMDA receptor agonist, and 2,3-pyridinedicarboxylic acid (QUIN), an agonist of the NMDA receptor subgroup containing the subunits NR2A and NR2B. The behavioral changes following KYNA were partially attenuated by QUIN alone. In conclusion, we suggest that KYNA functioned via the simultaneous inhibition of the α7nACh receptor and NMDA receptor subgroup containing the subunits NR2A and NR2B.
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The kinetics of neurotransmitter release was recognized recently as an important contributor to synaptic efficiency. Since adenosine is the ubiquitous modulator of presynaptic release in peripheral and central synapses, in the current project we studied the action of this purine on the timing of acetylcholine quantal release from motor nerve terminals in the skeletal muscle. Using extracellular recording from frog neuromuscular junction we tested the action of adenosine on the latencies of single quantal events in the pro-oxidant and antioxidant conditions. ⋯ Thus, adenosine which is generated at the neuromuscular junction from the breakdown of the co-transmitter ATP induces the synchronization of quantal events. The effect of adenosine on release timing should preserve the fidelity of synaptic transmission via "cost-effective" use of less transmitter quanta. Our findings also revealed important crosstalk between purinergic and redox modulation of synaptic processes which could take place in the elderly or in neuromuscular diseases associated with oxidative stress like lateral amyotrophic sclerosis.