Synaptic Soluble and Membrane-Bound Choline Acetyltransferase as a Marker of Cholinergic Function In Vitro and In Vivo

Захарова, Е. И.; Dudchenko, A. M.

doi:10.5772/58307

Cited by 5 publications

(12 citation statements)

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“…In the light and heavy synaptosomes of both the neocortex and the hippocampus, the activity of ChAT, a marker of cholinergic neurons, has a similar proportion. Together with usually detected differences in the response of ChAT in these synaptosomal fractions to the experimental impacts, this suggests the concentration of presynapses of cholinergic projective neurons in the light fractions of synaptosomes and presynapses of interneurons—in the heavy fraction of synaptosomes [ 24 , 25 , 28 ]. Hence, it is highly likely that the reciprocal changes in the activity of mChAT, observed after HBH in the hippocampus, took place in the presynapses of cholinergic projective neurons.…”

Section: Discussionmentioning

confidence: 92%

“…The advantage of such methodology was repeatedly seen, since the division of synaptosomes into sub-fractions allows the study and comparison of: (1) functionally different compartments of presynapses synaptic membranes and synaptoplasm; (2) minor biochemical, membrane-bound parameters whose changes are not detected in the total fractions and at the same time they are indicators of synaptic transmitter function. Moreover, we studied separately the synaptic components of the fractions of “light” and “heavy” synaptosomes, because they include the presynapses of functionally different cholinergic neuron populations [ 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

et al. 2020

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(1) Background. A one-time moderate hypobaric hypoxia (HBH) has a preconditioning effect whose neuronal mechanisms are not studied well. Previously, we found a stable correlation between the HBH efficiency and acoustic startle prepulse inhibition (PPI). This makes it possible to predict the individual efficiency of HBH in animals and to study its potential adaptive mechanisms. We revealed a bi-directional action of nicotinic α7 receptor agonist PNU-282987 and its solvent dimethyl sulfoxide on HBH efficiency with the level of PPI > or < 40%. (2) The aim of the present study was to estimate cholinergic mechanisms of HBH effects in different brain regions. (3) Methods: in rats pretested for PPI, we evaluated the activity of synaptic membrane-bound and water-soluble choline acetyltransferase (ChAT) in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex, hippocampus and caudal brainstem in the intact brain and after HBH. We tested the dose-dependent influence of PNU-282987 on the HBH efficiency. (4) Results: PPI level and ChAT activity correlated negatively in all brain structures of the intact animals, so that the values of the latter were higher in rats with PPI < 40% compared to those with PPI > 40%. After HBH, this ChAT activity difference was leveled in the neocortex and caudal brainstem, while for membrane-bound ChAT in the ‘light’ synaptosomal fraction of hippocampus, it was reversed to the opposite. In addition, a pharmacological study revealed that PNU-282987 in all used doses and its solvent displayed corresponding opposite effects on HBH efficiency in rats with different levels of PPI. (5) Conclusion: We substantiate that in rats with low and high PPI two opposite hippocampal cholinergic mechanisms are involved in hypoxic preconditioning, and both are implemented by forebrain projections via nicotinic α7 receptors. Possible causes of association between general protective adaptation, HBH, PPI, forebrain cholinergic system and hippocampus are discussed.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

et al. 2020

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“…Thus, compared with sChAT, the correlation of the activity of mChAT from light cortical synaptosomes with behavioural measures appeared later (on day 3) and was more stable (i.e., was seen also in rats trained for 5 days). Specific functions of sChAT and mChAT have been discussed in the literature (Cooper, 1994;Pyle et al, 2000;Pahud et al, 2003;Zakharova and Dudchenko, 2014). To bind to membrane structures, sChAT needs some modifications, in particular, phosphorylation of and binding with proteins in the plasma membrane (Pahud et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Activity of Choline Acetyltransferase From Different Synaptosomal Fractions at the Distinct Stages of Spatial Learning in the Morris Water Maze

Сторожева

Захарова

Proshin

2021

Front. Behav. Neurosci.

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Accumulated data have evidenced that brain cholinergic circuits play a crucial role in learning and memory; however, our knowledge about the participation of neocortical and hippocampal cholinergic systems in spatial learning needs to be refined. The aim of this study was to evaluate the association of the activity of membrane-bound and soluble choline acetyltransferase (ChAT) in the synaptosomal sub-fractions of the neocortex and hippocampus with performance of the spatial navigation task in the Morris water maze at different temporal stages of memory trace formation. To identify distinct stages of memory formation, rats were trained using a 5-day protocol with four trials per day. The mean escape latency for each trial was collected, and the entire dataset was subjected to principal component analysis. Based on the Morris water maze protocol, there were three relatively distinct stages of memory formation: days 1–2, day 3, and days 4–5. The remotely stored memory trace tested in repeated and reversal learning beginning on day 19 (14 days after the end of initial learning) was associated at the individual level mainly with performance during the second trial on day 21 (the third day or repeated or reversal learning). The ChAT activity data suggest the participation of cortical cholinergic projections mainly in the first stage of spatial learning (automatic sensory processing) and the involvement of hippocampal interneurons in the second stage (error-corrected learning). Cholinergic cortical interneurons participated mainly in the stage of asymptotic performance (days 4–5). It is advisable to evaluate other signalling pathways at the identified stages of memory formation.

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“…We substantiated that the nerve endings of this rat group may be outside NTS. Additionally, a correlation was found between the HBH-induced changes in activity of water-soluble ChAT in caudal brainstem and membrane-bound ChAT in pre-synapses of cortical projection neurons (Figure 6b,t h e cortical light synaptosomal fraction [124,125]) (r = +0.911, p <0 . 0 2 ,n = 6, Pearson's correlative test).…”

Section: In the High-resistant Ratsmentioning

confidence: 91%

“…In the intact rats, cChAT was activated in the cortical interneurons ( Figure 6c, the heavy fraction of synaptosomes [124,125]). There was no correlation between cChAT activity in the caudal brainstem and cortex in this rat group because of the absence of a direct link between the brain stem neurons and the cortical cholinergic interneurons.…”

Section: In the Intact Ratsmentioning

confidence: 99%

Hypoxic Preconditioning: The Multiplicity of Central Neurotransmitter Mechanisms and Method of Predicting Its Efficiency

Захарова¹,

Storozheva²,

Proshin³

et al. 2018

Hypoxia and Anoxia

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In rats, a single moderate hypobaric hypoxia (HBH) increased the resistance to severe hypoxia (SHBH). The HBH efficiency and neurotransmitter mechanisms of its preconditioning action were investigated by biochemical and pharmacological methods. It will be substantiated in the chapter: (1) HBH preconditioning has its own mechanisms that do not depend on an innate resistance to SHBH and prior hypoxic experience of rats; (2) the same preconditioning effect can be achieved by diverse neuronal pathways and synaptic plasticity means; (3) cholinergic and, presumably, serotoninergic, GABAergic and/or glutamatergic systems of the caudal brainstem, cortex and some other brain structures are involved in HBH realisation; (4) the rate of sensorimotor gating estimated in the model of acoustic startle pre-pulse inhibition (PPI) predicts the efficiency of hypoxic preconditioning and (5) the cholinergic system, including α7 nicotinic receptors, is involved in the mechanisms of HBH-PPI-dependent preconditioning effects.

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Synaptic Soluble and Membrane-Bound Choline Acetyltransferase as a Marker of Cholinergic Function In Vitro and In Vivo

Cited by 5 publications

References 159 publications

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

Evaluation of the Activity of Choline Acetyltransferase From Different Synaptosomal Fractions at the Distinct Stages of Spatial Learning in the Morris Water Maze

Hypoxic Preconditioning: The Multiplicity of Central Neurotransmitter Mechanisms and Method of Predicting Its Efficiency

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