Neuroscience
-
Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. ⋯ However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission.
-
Sensorineural hearing loss, as a consequence of acoustic trauma, aging, genetic defects or ototoxic drugs, is highly associated with irreversible damage of cochlear hair cells (HCs) and secondary degeneration of spiral ganglion (SG) cells. Cochlear implants (CIs), which bypass the lost HC function by direct electrical stimulation of the remaining auditory neurons, offer an effective therapy option. Several studies imply that components of the extracellular matrix (ECM) have a great impact on the adhesion and growth of spiral ganglion neurons (SGNs) during development. ⋯ The DSD-1 carbohydrate epitope is specifically localized to HC stereocilia and SG fibers. Interestingly, TN-C and the DSD-1-PG exhibit a mutually exclusive expression pattern, with the exception of a very restricted region beneath the habenula perforata, where SG neurites grow through the basilar membrane (BM) toward the HCs. The complementary expression of TN-C, LN, FN, and the DSD-1 epitope suggests that TN-C may act as an important boundary formation molecule in the developing postnatal mouse inner ear, which makes it a promising candidate to regulate neurite outgrowth in the light of CIs.
-
The tumor necrosis factor like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (Fn14), mediate inflammation and neuronal apoptosis in cerebral edema, ischemic stroke and multiple sclerosis. The downstream effectors and pathways linked to TWEAK-Fn14 signaling are strongly implicated in the pathology of Parkinson's disease (PD), thus indicating a putative role for TWEAK/Fn14 signaling in PD neurodegeneration. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, we aimed to determine whether genetic ablation or pharmacologic mitigation of the TWEAK protein and its Fn14 receptor affected substantia nigra and striatum Parkinsonian pathology. ⋯ Mitigating the effects of endogenous TWEAK protein using neutralizing antibody did affect MPTP-mediated neurotoxicity in the substantia nigra using the sub-acute model of MPTP (30mg/kg i.p. over five consecutive days). Neither TWEAK nor Fn14 genetic ablation led to attenuation of MPTP-toxicity in the acute model. These findings suggest that TWEAK signaling might be an aspect of MPTP-mediated neuropathology and be involved in the overall neurodegenerative pathology of PD.
-
Acetylcholinesterase plays a major role in neuromuscular transmission and is regulated by neuromuscular activity. Since fast-twitch motor units are recruited with increased motor demand, we examined acetylcholinesterase regulation in rat leg muscles following treadmill training. ⋯ Electron microscopy showed that acetylcholinesterase increased in postjunctional folds and primary cleft, where it was added adjacent to the postsynaptic muscle membrane. Thus, although the primary acetylcholinesterase at the neuromuscular junction is the collagen-tailed asymmetric isoform associated with synaptic basal lamina, physiological demands such as strenuous exercise, or potentially pathological conditions, can selectively recruit the membrane-bound acetylcholinesterase tetramer to the synapse for optimal synaptic transmission.