| Autor: |
Więckowska, Angelika, Gajewska‐Woźniak, Olga, Głowacka, Anna, Ji, Benjun, Grycz, Kamil, Czarkowska‐Bauch, Julita, Skup, Małgorzata |
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| Zdroj: |
Journal of Neurochemistry; Nov2018, Vol. 147 Issue 3, p361-379, 19p |
| Abstrakt: |
Complete thoracic spinal cord transection (SCT) impairs excitatory cholinergic inputs to ankle extensor (soleus; Sol) but not to flexor (tibialis anterior; TA) α‐motoneurons (MNs) modifiable by locomotor training applied post‐transection. The purpose of this study was to investigate whether Sol and TA MNs adapt to changes in cholinergic environment by differential regulation of their muscarinic receptors M2 (M2R). We examined Chrm2 (M2R gene) transcript level, high‐affinity 3‐quinuclidinyl benzilate‐3H ([3H]QNB) ligand binding, distribution and density of M2R immunolabeling in lumbar (L) segments in intact and SCT rats, with or without inclusion of 5‐week treadmill locomotor training. We show that at the second week after SCT the levels of Chrm2 transcript are reduced in the L3–6 segments, with [3H]QNB binding decreased selectively in the L5–6 segments, where ankle extensor MNs are predominantly located. At 5 weeks after SCT, [3H]QNB binding differences between the L3–4 and L5–6 segments are maintained, accompanied by higher density of M2R immunolabeling in the plasma membrane and cytoplasm of TA than Sol MNs and by enriched synaptic versus extrasynaptic M2R pools (52% TA vs. 25% Sol MNs). Training normalized M2R in TA MNs, improved locomotion, and reduced frequency of clonic episodes. Our findings indicate higher sensitivity of TA than Sol MNs to cholinergic signaling after SCT, which might shorten flexor twitches duration and contribute to generation of clonic movements. Synaptic enrichment in M2R density may reflect a compensatory mechanism activated in TA and Sol MNs to different extent in response to reduced strength of cholinergic signaling to each MN pool. Open Practices: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/ Spinal cord transection causes hypercholinergic state and clonic movements in paraplegic rats despite of reduced cholinergic inputs to the ankle extensor (Sol) but not to flexor (TA) α‐motoneurons (MNs). We show a deepening of that imbalance postsynaptically: muscarinic acetylcholine receptor type 2 (M2R) density in the synaptic regions of cell membrane (orange/red regions) and in cytoplasm was increased more in TA than Sol MNs. M2R enrichment may reflect a maladaptive mechanism activated in TA and Sol to different extent. Locomotor training normalized M2R in TA MNs, improved locomotion and reduced frequency of clonic episodes. [ABSTRACT FROM AUTHOR] |
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