Neuroscience
-
In the CNS, chemokines and chemokine receptors are involved in pleiotropic physiological and pathological activities. Several evidences demonstrated that chemokine signaling in the CNS plays key homeostatic roles and, being expressed on neurons, glia and endothelial cells, chemokines mediate the bidirectional cross-talk among parenchymal cells. ⋯ In this review we summarize the evidence that chemokines (CXCL12, CX3CL1, CXCL16 and CCL2) modulate neuroprotective processes upon different noxious stimuli and participate to orchestrate neurons-microglia-astrocytes action to preserve and limit brain damage. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
Review
'Fragmentation' of NMJs: a sign of degeneration or regeneration? A long journey with many junctions.
Mammalian neuromuscular junctions (NMJs) often consist of curved bands of synaptic contact, about 3-6 μm wide, which resemble pretzels. This contrasts with the NMJs of most animal species which consist of a cluster of separate synaptic spots, each of which is also about 3-6 μm across. In a number of situations, including a variety of disease states as well as normal ageing, mammalian NMJs acquire a more 'fragmented' appearance that resembles somewhat that of other species. ⋯ Further, where appropriate studies have been performed, no evidence of a correlation between the degree of fragmentation and the efficacy of transmission has emerged. It may therefore be more appropriate to consider NMJ 'fragmentation' as a form of regeneration, rather than of degeneration. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
Review
Presynaptic Black Box Opened by Pioneers at Biophysics Department in University College London.
The mechanism of chemical synaptic transmission was elucidated at the frog neuromuscular junction (NMJ) and at the squid giant synapse by Katz, Miledi and other researchers. Later progress in molecular biology revealed numerous types of proteins in mammalian central synapses. To establish molecular-functional correlation in synaptic transmission, it now seems essential to re-address the fundamental mechanisms at mammalian central synapses. ⋯ However, at the calyx of Held, unlike at the squid synapse, the input-output relationship had a wide safety margin, protecting transmitter release from a diminishment of presynaptic action potentials. As in the NMJ, Ca2+ remaining in the cytosol after action potential facilitates subsequent release. As a downstream mechanism of this residual Ca2+, a Ca2+-induced Ca2+ channel activation via high-affinity Ca2+ binding proteins was discovered at mammalian central synapses.
-
Extracellular adenosine triphosphate (ATP) participates in maintaining the vascular tone in the CNS, particularly in the retina, via the tonic activity of ligand gated activated P2X1 receptors. P2X1 receptors are characterized by their high affinity for ATP and their strong desensitization to concentrations of ATP that are 200-fold lower than their EC50. The mechanism behind P2X1 tonic activity remains unclear. ⋯ In the presence of extracellular Ca2+ the activity of hP2X1 receptors is greatly amplified by its coupling with Ca2+-activated Cl- channels. Future studies addressing the relationship between hP2X1 receptors and Ca2+-activated Cl- channels in vascular smooth muscle cells should provide information about additional mechanisms that regulate the vascular tone and their potential as pharmaceutical targets. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
Attention deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric childhood disorder, characterized by hyperactivity, impulsivity and impaired attention, treated most frequently with methylphenidate (MPH). For children and adults with ADHD who do not respond satisfactorily or do not tolerate well stimulants such as MPH or D-Amphetamine, for them the alternative is to use Atomoxetine (ATX), a norepinephrine (NE) transporter inhibitor that increase extracellular NE. We examined the effects of ATX on behavior and hippocampal synaptic plasticity in the murine prenatal nicotine exposure (PNE) model of ADHD. ⋯ Paired-pulse ratios (PPR) were not significantly different for any condition. These results indicate that administration of ATX in a PNE model of ADHD reestablishes TBS-dependent LTP in CA3-CA1 synapses. The results suggest postsynaptic changes in synaptic plasticity as part of the mechanisms that underlie improvement of ADHD symptoms induced by ATX.