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Heterogeneous responses to antioxidants in noradrenergic neurons of the Locus coeruleus indicate differing susceptibility to free radical content.

de Oliveira RB, Gravina FS, Lim R, Brichta AM, Callister RJ, van Helden DF - Oxid Med Cell Longev (2012)

Bottom Line: In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants.Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca(2+) concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential.If this is the case, there may be a protective role for antioxidant therapies.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences and Pharmacy, The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW 2308, Australia.

ABSTRACT
The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca(2+) concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca(2+)-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies.

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Related in: MedlinePlus

Impact of DTT treatment in the pacemaker process of LC neurons. (a) Table demonstrating the effect of 1 mM DTT in the spontaneous firing of LC neurons and comparison of values obtained for AP before (ACSF) and 180 s after 1 mM DTT treatment (n = 19 for spontaneous firing and n = 28 for AP comparison). (b) Averaged APs demonstrating comparison before (ACSF) and after 180 s after 1 mM DDT treatment (n = 28). Hyperpolarizing group was excluded from comparison demonstrated in (a) and (b) due to lack of APs at 180 s treatment. (c) and (d), Example for recordings demonstrating the two minor effects induced by 1 mM DTT where neurons hyperpolarized and ceased firing (c) and stopped firing without hyperpolarization (d) (n = 19).
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fig3: Impact of DTT treatment in the pacemaker process of LC neurons. (a) Table demonstrating the effect of 1 mM DTT in the spontaneous firing of LC neurons and comparison of values obtained for AP before (ACSF) and 180 s after 1 mM DTT treatment (n = 19 for spontaneous firing and n = 28 for AP comparison). (b) Averaged APs demonstrating comparison before (ACSF) and after 180 s after 1 mM DDT treatment (n = 28). Hyperpolarizing group was excluded from comparison demonstrated in (a) and (b) due to lack of APs at 180 s treatment. (c) and (d), Example for recordings demonstrating the two minor effects induced by 1 mM DTT where neurons hyperpolarized and ceased firing (c) and stopped firing without hyperpolarization (d) (n = 19).

Mentions: Dithiothreitol (DTT; 1 mM) also produced varied effects on spontaneous firing activity of 19 LC neurons (Figure 3(a)). AP firing was not significantly altered in 10 neurons and was abolished in 4 due to marked hyperpolarization (Figure 3(c)), and 3 neurons ceased AP firing with no apparent hyperpolarization (Figures 3(a) and 3(d)). A small portion of the neurons (2/19) increased their AP firing rate after depolarization (2 of 19; Figure 3(a)). AP comparison demonstrated no differences in AP shape (Figure 3(b)) as was the case for Trolox.


Heterogeneous responses to antioxidants in noradrenergic neurons of the Locus coeruleus indicate differing susceptibility to free radical content.

de Oliveira RB, Gravina FS, Lim R, Brichta AM, Callister RJ, van Helden DF - Oxid Med Cell Longev (2012)

Impact of DTT treatment in the pacemaker process of LC neurons. (a) Table demonstrating the effect of 1 mM DTT in the spontaneous firing of LC neurons and comparison of values obtained for AP before (ACSF) and 180 s after 1 mM DTT treatment (n = 19 for spontaneous firing and n = 28 for AP comparison). (b) Averaged APs demonstrating comparison before (ACSF) and after 180 s after 1 mM DDT treatment (n = 28). Hyperpolarizing group was excluded from comparison demonstrated in (a) and (b) due to lack of APs at 180 s treatment. (c) and (d), Example for recordings demonstrating the two minor effects induced by 1 mM DTT where neurons hyperpolarized and ceased firing (c) and stopped firing without hyperpolarization (d) (n = 19).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3345253&req=5

fig3: Impact of DTT treatment in the pacemaker process of LC neurons. (a) Table demonstrating the effect of 1 mM DTT in the spontaneous firing of LC neurons and comparison of values obtained for AP before (ACSF) and 180 s after 1 mM DTT treatment (n = 19 for spontaneous firing and n = 28 for AP comparison). (b) Averaged APs demonstrating comparison before (ACSF) and after 180 s after 1 mM DDT treatment (n = 28). Hyperpolarizing group was excluded from comparison demonstrated in (a) and (b) due to lack of APs at 180 s treatment. (c) and (d), Example for recordings demonstrating the two minor effects induced by 1 mM DTT where neurons hyperpolarized and ceased firing (c) and stopped firing without hyperpolarization (d) (n = 19).
Mentions: Dithiothreitol (DTT; 1 mM) also produced varied effects on spontaneous firing activity of 19 LC neurons (Figure 3(a)). AP firing was not significantly altered in 10 neurons and was abolished in 4 due to marked hyperpolarization (Figure 3(c)), and 3 neurons ceased AP firing with no apparent hyperpolarization (Figures 3(a) and 3(d)). A small portion of the neurons (2/19) increased their AP firing rate after depolarization (2 of 19; Figure 3(a)). AP comparison demonstrated no differences in AP shape (Figure 3(b)) as was the case for Trolox.

Bottom Line: In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants.Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca(2+) concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential.If this is the case, there may be a protective role for antioxidant therapies.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences and Pharmacy, The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW 2308, Australia.

ABSTRACT
The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca(2+) concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca(2+)-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies.

Show MeSH
Related in: MedlinePlus