Neuroscience
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Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. ⋯ Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves.
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In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. ⋯ Furthermore, using single-cell RT-PCR, all four connexins were detected in different subtypes of HCs, suggesting overlapping expression patterns. Thus, the composition of gj mediating homologous coupling between subtypes of carp HCs appears to be more complex than expected. Moreover, BLAST searches of the preliminary carp genome, using novel sequences as query, suggest that most of the analyzed connexin genes are duplicated in carp.
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GM1 gangliosides (GM1) are acidic glycosphingolipids that are present in cell membranes and lipid raft domains, being particularly abundant in central nervous systems. GM1 participate in modulating cell membrane properties, intercellular recognition, cell regulation, and signaling. We previously demonstrated that GM1 are expressed inside astrocytes but not on the cell surface. ⋯ Interestingly, this increase in GM1 expression induced the accumulation of autophagosomes in astrocytes. Moreover, the effect of haloperidol on the σ1R induced a decrease in GM1 in the cellular membrane of astrocytes. These findings suggested that the effects of haloperidol on the σ1R induced GM1 accumulation in the autophagosomes of astrocytes through activating the ERK pathway and a decrease in GM1 expression on the cell surface.
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Although it is still debated whether vasoconstriction underlies migraine resolution by triptans, they are not recommended in patients at cardiovascular risk. However, relationship between stroke incidence and triptan use is unclear, and it is unknown whether acute or chronic use of these drugs worsens ischemic brain injury. To address this issue, we investigated the effect of clinically-relevant doses of the potent cerebral artery vasoconstrictor eletriptan on cerebral blood flow (CBF) and brain infarct volumes, as well as on expression of genes involved in cerebrovascular regulation. ⋯ Finally, chronic eletriptan reduced brain mRNAs for PACAP and VIP, leaving unaffected those for 5HT1B/DR and CGRP. No significant transcript changes were found in dura mater. Data suggest that the impact of triptans on cerebral hemodynamic should be re-evaluated, as well as their propensity to increase stroke risk in migraineurs.
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Cannabinoid type-1 (CB1) and transient receptor potential vanilloid type-1 (TRPV1) receptors may have opposite roles in modulating neural activity and, consequently, in regulating the stress response. These receptors are widely expressed in several brain structures, including the ventral medial prefrontal cortex (vmPFC). The functional consequences of the interaction between CB1 and TRPV1, however, have scarcely been explored. ⋯ Furthermore, the co-administration of URB597 and SB366791 in sub-effective doses induced an antidepressant-like effect in the FST. Additionally, the antidepressant-like effect of AA-5HT was prevented by the CB1 antagonist. Together, these results suggest that both, CB1 and TRPV1 receptors located in the vmPFC are involved in the behavioral responses to stress, although in opposite ways.