ATF3 is a novel nuclear marker for migrating ependymal stem cells in the rat spinal cord

Mladinić, Miranda; Bianchetti, Elena; Dekanić, Ana; Mazzone, Graciela L.; Nistri, Andrea

doi:10.1016/j.scr.2014.03.006

Cited by 35 publications

(32 citation statements)

References 49 publications

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“…Western blot analysis was performed on whole brainstem treated according to the protocols described above and previously published (Mladinic et al . ). Tissues were lysed in CHAPS buffer solution (0.5% CHAPS, 50 m m Tris pH 7.5, 1 m m EDTA, 150 m m NaCl, 10% glycerol plus protease inhibitors mixture; Complete, Roche Applied Science, Basel, Switzerland) and immunoblotted with rabbit anti‐UGGT (1:7000, Abcam) and mouse anti‐β‐actin (1:2000, Sigma) antibodies.…”

Section: Methodsmentioning

confidence: 97%

Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Corsini

Tortora

Nistri

2016

The Journal of Physiology

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Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 μm nicotine, whereas nAChR antagonists facilitated burst emergence in non-burster cells. Furthermore, nicotine inhibited excitatory transmission and enhanced synaptic inhibition. Strong neuroprotection by nicotine prevented the HM loss observed after 4 h of TBOA exposure. This neuroprotective action was due to suppression of downstream effectors of neurotoxicity such as increased intracellular levels of reactive oxygen species, impaired energy metabolism and upregulated genes involved in endoplasmic reticulum (ER) stress. In addition, HMs surviving TBOA toxicity often expressed UDP-glucose glycoprotein glucosyltransferase, a key element in repair of misfolded proteins: this phenomenon was absent after nicotine application, indicative of ER stress prevention. Our results suggest nAChRs to be potential targets for inhibiting excitotoxic damage of motoneurons at an early stage of the neurodegenerative process.

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Section: Methodsmentioning

confidence: 97%

Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Corsini

Tortora

Nistri

2016

The Journal of Physiology

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“…70 Total lysates, cytoplasmic and membrane fractions were analyzed. Total lysates were obtained by homogenizing samples in CHAPS buffer solution (0.5% CHAPS, 50 mM Tris pH 7.5, 1 mM EDTA, 150 mM NaCl, 10% glycerol plus protease inhibitors mixture and reducing agents; Complete, Roche Applied Science, Basel, Switzerland; and Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

et al. 2017

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Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca2+ transients time locked among nearby HMs, whose number fell by about 30% 4 h later. As nicotine or the gap junction blocker carbenoxolone suppressed bursting, we studied connexin 36 (Cx36), which constitutes gap junctions in neurons and found it largely expressed by HMs. Cx36 was downregulated when nicotine or carbenoxolone was co-applied with TBOA. Expression of Cx36 was preferentially observed in cytosolic rather than membrane fractions after nicotine and TBOA, suggesting protein redistribution with no change in synthesis. Nicotine raised the expression of heat shock protein 70 (Hsp70), a protective factor that binds the apoptotic-inducing factor (AIF) whose nuclear translocation is a cause of cell death. TBOA increased intracellular AIF, an effect blocked by nicotine. These results indicate that activation of neuronal nicotinic receptors is an early tool for protecting motoneurons from excitotoxicity and that this process is carried out via the combined decrease in Cx36 activity, overexpression of Hsp70 and fall in AIF translocation. Thus, retarding or inhibiting HM death may be experimentally achieved by targeting one of these processes leading to motoneuron death.

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“…This could be one of the first pieces of evidence supporting the hypothesis of Molofsky and Deneen (2015) on the as-yet-undefined presence of a second wave of migration of astrocyte precursors from the CC area to the periphery. Migration of cells from the CC lining toward the ventral and dorsal funiculi, as proposed by Mladinic et al (2014) and Mladinic and Nistri (2015) for their in vitro model, could be another explanation for this phenomenon. A significant decline in unit cellularity between P8 and P15 was also observed in mice (unpublished results) but was not investigated in more detail because it was not the objective of this study.…”

Section: Assessment Of the Cellularity Of The CC Lining In The Referementioning

confidence: 79%

Quantitative analyses of cellularity and proliferative activity reveals the dynamics of the central canal lining during postnatal development of the rat

Matiašová

Ševc

Tomori

et al. 2016

J of Comparative Neurology

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According to previous opinion, the derivation of neurons and glia from the central canal (CC) lining of the spinal cord in rodents should occur in the embryonic period. Reports of the mitotic activity observed in the lining during postnatal development have often been contradictory, and proliferation was ascribed to the generation of ependymocytes, which are necessary for the elongation of CC walls. Our study quantifies the intensity of proliferation and determines the cellularity of the CC lining in reference to lumbar spinal segment L4 during the postnatal development of rats. The presence of dividing cells peaks in the CC lining on postnatal day 8 (P8), with division occurring in 19.2% ± 3.2% of cells. In adult rats, 3.6% ± 0.9% of cells still proliferate, whereas, in mice, 10.3% ± 2.3% of cells at P8 and only 0.6% ± 0.2% of cells in the CC lining in adulthood are proliferating. In the rat, the length of the cell cycle increases from 100.3 ± 35.7 hours at P1 to 401.4 ± 80.6 hours at P43, with a sudden extension between P15 and P22. Despite the intensive proliferation, the total cellularity of the CC lining at the L4 spinal segment significantly descended in from P8 to P15. According to our calculations, the estimated cellularity was significantly higher compared with the measured cellularity of the CC lining at P15. Our results indicate that CC lining serves as a source of cells beyond ependymal cells during the first postnatal weeks of the rat. J. Comp. Neurol. 525:693-707, 2017. © 2016 Wiley Periodicals, Inc.

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ATF3 is a novel nuclear marker for migrating ependymal stem cells in the rat spinal cord

Cited by 35 publications

References 49 publications

Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

Quantitative analyses of cellularity and proliferative activity reveals the dynamics of the central canal lining during postnatal development of the rat

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