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Central neuroplasticity and decreased heart rate variability after particulate matter exposure in mice.

Pham H, Bonham AC, Pinkerton KE, Chen CY - Environ. Health Perspect. (2009)

Bottom Line: We also determined the effect of iron on PM-exposure-induced decrease in HRV.Iron-soot exposure had no significant effect on resting membrane potential but decreased spiking responses of the identified cardiac vagal neurons to depolarizations (p < 0.05).The decreased spiking response was accompanied with a higher minimal depolarizing current required to evoke spikes and a lower peak discharge frequency.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA

ABSTRACT

Background: Epidemiologic studies show that exposure to fine particulate matter [aerodynamic diameter < or = 2.5 microm (PM(2.5))] increases the total daily cardiovascular mortality. Impaired cardiac autonomic function, which manifests as reduced heart rate variability (HRV), may be one of the underlying causes. However, the cellular mechanism(s) by which PM(2.5) exposure induces decreased HRV is not known.

Objectives: We tested the hypothesis that exposure to PM(2.5) impairs HRV by decreasing the excitability of the cardiac vagal neurons in the nucleus ambiguus. We also determined the effect of iron on PM-exposure-induced decrease in HRV.

Methods: We measured 24-hr HRV in time domains from electrocardiogram telemetry recordings obtained in conscious, freely moving mice after 3 days of exposure to PM(2.5) in the form of soot only or iron-soot. In parallel studies, we determined the intrinsic properties of identified cardiac vagal neurons, retrogradely labeled with a fluorescent dye applied to the sinoatrial node.

Results: Soot-only exposure decreased short-term HRV (root mean square of successive difference). With the addition of iron, all HRV parameters were significantly reduced. In nonexposed mice, vagal blockade significantly reduced all HRV parameters, suggesting that HRV is, in part, under vagal regulation in mice. Iron-soot exposure had no significant effect on resting membrane potential but decreased spiking responses of the identified cardiac vagal neurons to depolarizations (p < 0.05). The decreased spiking response was accompanied with a higher minimal depolarizing current required to evoke spikes and a lower peak discharge frequency.

Conclusions: The data suggest that PM-induced neuroplasticity of cardiac vagal neurons may be one mechanism contributing to the cardiovascular consequences associated with PM(2.5) exposure seen in humans.

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Related in: MedlinePlus

(A) An identified cardiac vagal neuron viewed at 40×: the neuron viewed with IR-DIC (a), the neuron viewed with fluorescence filter set (b), overlay of the IR-DIC and fluorescence images (c), and neuron with patch electrode in whole-cell configuration (d). Bar = 50 μm. (B) Schematic drawing showing composite of recording sites (left) and the brainstem slice viewed at 5×. Abbreviations: LRt, lateral reticular nucleus; NA, nucleus ambiguus; NTS, nucleus tractus solitarii; Py, pyramidal tract; Sp5, spinal trigeminal nucleus; 12, hypoglossal nucleus. Bar = 500 μm.
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f6-ehp-117-1448: (A) An identified cardiac vagal neuron viewed at 40×: the neuron viewed with IR-DIC (a), the neuron viewed with fluorescence filter set (b), overlay of the IR-DIC and fluorescence images (c), and neuron with patch electrode in whole-cell configuration (d). Bar = 50 μm. (B) Schematic drawing showing composite of recording sites (left) and the brainstem slice viewed at 5×. Abbreviations: LRt, lateral reticular nucleus; NA, nucleus ambiguus; NTS, nucleus tractus solitarii; Py, pyramidal tract; Sp5, spinal trigeminal nucleus; 12, hypoglossal nucleus. Bar = 500 μm.

Mentions: Our data suggest that the cardiac vagal limb of the autonomic nervous system plays an important role in HRV regulation and that the PM2.5-exposure–induced decrease in HRV may be due to exposure-induced neuroplasticity in cardiac vagal neurons. To better define the cellular mechanisms underlying the PM2.5-exposure–induced decrease in HRV, we performed electrophysiologic experiments on cardiac vagal neurons in the NA that were identified by the presence of fluorescence dye (Figure 6). PM2.5 exposure in the form of iron-soot decreased neuronal excitability to depolarizing current injections (100–400 pA). Figure 7A shows examples of the spiking responses of cardiac vagal neurons from an FA and a PM-exposed mouse. The neuron from the PM-exposed mouse discharged fewer spikes than did the FA-exposed mouse at the same injected currents. The group data (Figure 7B) illustrate that the total number of spikes discharged in response to depolarizing current injections was significantly lower in the mice exposed to PM2.5 (two-way ANOVA: exposure, p = 0.071; current, p < 0.001; interaction, p = 0.018).


Central neuroplasticity and decreased heart rate variability after particulate matter exposure in mice.

Pham H, Bonham AC, Pinkerton KE, Chen CY - Environ. Health Perspect. (2009)

(A) An identified cardiac vagal neuron viewed at 40×: the neuron viewed with IR-DIC (a), the neuron viewed with fluorescence filter set (b), overlay of the IR-DIC and fluorescence images (c), and neuron with patch electrode in whole-cell configuration (d). Bar = 50 μm. (B) Schematic drawing showing composite of recording sites (left) and the brainstem slice viewed at 5×. Abbreviations: LRt, lateral reticular nucleus; NA, nucleus ambiguus; NTS, nucleus tractus solitarii; Py, pyramidal tract; Sp5, spinal trigeminal nucleus; 12, hypoglossal nucleus. Bar = 500 μm.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2737024&req=5

f6-ehp-117-1448: (A) An identified cardiac vagal neuron viewed at 40×: the neuron viewed with IR-DIC (a), the neuron viewed with fluorescence filter set (b), overlay of the IR-DIC and fluorescence images (c), and neuron with patch electrode in whole-cell configuration (d). Bar = 50 μm. (B) Schematic drawing showing composite of recording sites (left) and the brainstem slice viewed at 5×. Abbreviations: LRt, lateral reticular nucleus; NA, nucleus ambiguus; NTS, nucleus tractus solitarii; Py, pyramidal tract; Sp5, spinal trigeminal nucleus; 12, hypoglossal nucleus. Bar = 500 μm.
Mentions: Our data suggest that the cardiac vagal limb of the autonomic nervous system plays an important role in HRV regulation and that the PM2.5-exposure–induced decrease in HRV may be due to exposure-induced neuroplasticity in cardiac vagal neurons. To better define the cellular mechanisms underlying the PM2.5-exposure–induced decrease in HRV, we performed electrophysiologic experiments on cardiac vagal neurons in the NA that were identified by the presence of fluorescence dye (Figure 6). PM2.5 exposure in the form of iron-soot decreased neuronal excitability to depolarizing current injections (100–400 pA). Figure 7A shows examples of the spiking responses of cardiac vagal neurons from an FA and a PM-exposed mouse. The neuron from the PM-exposed mouse discharged fewer spikes than did the FA-exposed mouse at the same injected currents. The group data (Figure 7B) illustrate that the total number of spikes discharged in response to depolarizing current injections was significantly lower in the mice exposed to PM2.5 (two-way ANOVA: exposure, p = 0.071; current, p < 0.001; interaction, p = 0.018).

Bottom Line: We also determined the effect of iron on PM-exposure-induced decrease in HRV.Iron-soot exposure had no significant effect on resting membrane potential but decreased spiking responses of the identified cardiac vagal neurons to depolarizations (p < 0.05).The decreased spiking response was accompanied with a higher minimal depolarizing current required to evoke spikes and a lower peak discharge frequency.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA

ABSTRACT

Background: Epidemiologic studies show that exposure to fine particulate matter [aerodynamic diameter < or = 2.5 microm (PM(2.5))] increases the total daily cardiovascular mortality. Impaired cardiac autonomic function, which manifests as reduced heart rate variability (HRV), may be one of the underlying causes. However, the cellular mechanism(s) by which PM(2.5) exposure induces decreased HRV is not known.

Objectives: We tested the hypothesis that exposure to PM(2.5) impairs HRV by decreasing the excitability of the cardiac vagal neurons in the nucleus ambiguus. We also determined the effect of iron on PM-exposure-induced decrease in HRV.

Methods: We measured 24-hr HRV in time domains from electrocardiogram telemetry recordings obtained in conscious, freely moving mice after 3 days of exposure to PM(2.5) in the form of soot only or iron-soot. In parallel studies, we determined the intrinsic properties of identified cardiac vagal neurons, retrogradely labeled with a fluorescent dye applied to the sinoatrial node.

Results: Soot-only exposure decreased short-term HRV (root mean square of successive difference). With the addition of iron, all HRV parameters were significantly reduced. In nonexposed mice, vagal blockade significantly reduced all HRV parameters, suggesting that HRV is, in part, under vagal regulation in mice. Iron-soot exposure had no significant effect on resting membrane potential but decreased spiking responses of the identified cardiac vagal neurons to depolarizations (p < 0.05). The decreased spiking response was accompanied with a higher minimal depolarizing current required to evoke spikes and a lower peak discharge frequency.

Conclusions: The data suggest that PM-induced neuroplasticity of cardiac vagal neurons may be one mechanism contributing to the cardiovascular consequences associated with PM(2.5) exposure seen in humans.

Show MeSH
Related in: MedlinePlus