Example Natural Science Poster_Neuroscience
Breathing and Olfactory CO2 Chemoreceptors: Implications in SIDS Jessica Kenemuth and E. Lee Coates Neuroscience Program, Allegheny College, Meadville, PA
Introduction
Methods
“Sudden Infant Death Syndrome (SIDS) is the unexpected, sudden death of a child under age 12 months in which an autopsy does not show an explainable cause of death” (NIH, 2008). The “Triple Risk Model” proposes that SIDS is due to the intersection of a critical developmental period, an exogenous stressor, and an abnormality in cardiorespiratory control (Filano and Kinney, 1990).
Results
Conclusions
Breathing Study
Breathing Study • Breathing was measured in neonatal mice in response to 0, 4, 8% CO2
Breathing Study • Ventilation was successfully measured in neonatal mice.
Ventilatory Response to CO2 - Day 3
• Mice were placed in a plesthysmograph chamber (see Figure below)
Period 1
Pre-CO2
• Breathing responses were measured on days 1,2,3,5, and 8 after birth
Period 2
• Ventilation became more regular with age, indicating that central chemoreceptors are not fully developed at birth.
0% CO2
Breathing Study The objective of this study was to determine if neonatal mice could be used to investigate portions of the “Triple Risk Model” Highest rate 3-6 months
Critical Developmental Period
Electrophysiology Study
4% CO2
High CO2, Low O2, High Temp
• Application of Acetazolamide inhibited the receptor responses to CO2 • Application of QAS and did not affect receptor responses to CO2.
8% CO2
• We conclude that intracellular CA is necessary for the detection of CO2 by olfactory CO2 receptors.
1 sec
Exogenous Stressor
• Extracellular CA does not seem to play a role in the detection of CO2 by olfactory CO2 receptors.
Age-Related Ventilatory Response to CO2
Filiano and Kinney, 1990
Other Risk Factors: - Prone sleeping - Loose bedding - Smoking - Bed sharing - Pre-term birth
Abnormalities in Cardiorespiratory Control
1 minute of 0, 4, or 8% CO2
Pre-CO2
“Back to Sleep” campaign reduced SIDS from 1.2 cases/1000 live births in 1993 to 0.5 cases/1000 live birth in 2003
Coates EL, Silvis ML. (1999) Age-related changes in the ventilatory response to inspired CO2 in neonatal rats. Respiration Physiology 118: 173-179. Day 8 (8% CO2)
Electrophysiology Study
• Receptor responses to CO2 were recorded from the olfactory epithelium
The objective of this part of the study was to record from CO2 olfactory receptors in the mouse to determine the transduction mechanisms used to detect CO2.
• Membrane permeable (acetazolamide) or membrane impermeable (QAS) carbonic anhydrase inhibitors were applied to the olfactory epithelium.
Odorant Odorant
Olfactory receptor response to CO2 (Before and after inhibition with Acetazolamide or QAS)
Electro-olfactogram (EOG) electrode
Mucosal layer Cilia
AC R G CO2 + H2O
cAMP
Mature olfactory neuron
CA H2CO3
Supporting cell H+ + HCO3 -
?
Filiano JJ, Kinney HC. (1994) A perspective on neuropathologic findings in victims of the sudden infant death syndrome: The triple risk model. Biology of the Neonate 65: 194-197.
Electrophysiology Study
Na+, Ca2+
CO2
Coates EL. (2001) Olfactory CO2 chemoreceptors. Respiration Physiology 129: 219-229. 1 sec
Immature neuron Na+, Ca2+
Basement membrane
Axons
EOG Amplitude (% max baseline)
Specifically, we sought to determine the role of intracellular and extracellular carbonic anhydrase (CA)
CO2
References
Period 2
Electrophysiology Study
ATP
Period 2
Day 3 (8% CO2)
0% CO2
Period 1
Period 1
Pre-CO2
0% CO2
• Mice exhibited an age-related increase in ventilation with increasing CO2 concentrations.
120
Before - Acetazolamide After - Acetazolamide
N=7
120
100
100
80
80
60
60
40
40
20
20
0
0
0
5
10 15 20 25 30 35 40 45 50
% CO2
Before - QAS After - QAS
Hunt CE, Hauck FR. (2006) Sudden infant death syndrome. Canadian Medical Association Journal 174: 1861-1869. National Institute of Health (2008) www.NIH.gov
N=6
Acknowledgements We thank Dr. and Mrs. Edward Shanbrom for generously funding this project. 0
5
10 15 20 25 30 35 40 45 50
% CO2
Introduction
Methods
“Sudden Infant Death Syndrome (SIDS) is the unexpected, sudden death of a child under age 12 months in which an autopsy does not show an explainable cause of death” (NIH, 2008). The “Triple Risk Model” proposes that SIDS is due to the intersection of a critical developmental period, an exogenous stressor, and an abnormality in cardiorespiratory control (Filano and Kinney, 1990).
Results
Conclusions
Breathing Study
Breathing Study • Breathing was measured in neonatal mice in response to 0, 4, 8% CO2
Breathing Study • Ventilation was successfully measured in neonatal mice.
Ventilatory Response to CO2 - Day 3
• Mice were placed in a plesthysmograph chamber (see Figure below)
Period 1
Pre-CO2
• Breathing responses were measured on days 1,2,3,5, and 8 after birth
Period 2
• Ventilation became more regular with age, indicating that central chemoreceptors are not fully developed at birth.
0% CO2
Breathing Study The objective of this study was to determine if neonatal mice could be used to investigate portions of the “Triple Risk Model” Highest rate 3-6 months
Critical Developmental Period
Electrophysiology Study
4% CO2
High CO2, Low O2, High Temp
• Application of Acetazolamide inhibited the receptor responses to CO2 • Application of QAS and did not affect receptor responses to CO2.
8% CO2
• We conclude that intracellular CA is necessary for the detection of CO2 by olfactory CO2 receptors.
1 sec
Exogenous Stressor
• Extracellular CA does not seem to play a role in the detection of CO2 by olfactory CO2 receptors.
Age-Related Ventilatory Response to CO2
Filiano and Kinney, 1990
Other Risk Factors: - Prone sleeping - Loose bedding - Smoking - Bed sharing - Pre-term birth
Abnormalities in Cardiorespiratory Control
1 minute of 0, 4, or 8% CO2
Pre-CO2
“Back to Sleep” campaign reduced SIDS from 1.2 cases/1000 live births in 1993 to 0.5 cases/1000 live birth in 2003
Coates EL, Silvis ML. (1999) Age-related changes in the ventilatory response to inspired CO2 in neonatal rats. Respiration Physiology 118: 173-179. Day 8 (8% CO2)
Electrophysiology Study
• Receptor responses to CO2 were recorded from the olfactory epithelium
The objective of this part of the study was to record from CO2 olfactory receptors in the mouse to determine the transduction mechanisms used to detect CO2.
• Membrane permeable (acetazolamide) or membrane impermeable (QAS) carbonic anhydrase inhibitors were applied to the olfactory epithelium.
Odorant Odorant
Olfactory receptor response to CO2 (Before and after inhibition with Acetazolamide or QAS)
Electro-olfactogram (EOG) electrode
Mucosal layer Cilia
AC R G CO2 + H2O
cAMP
Mature olfactory neuron
CA H2CO3
Supporting cell H+ + HCO3 -
?
Filiano JJ, Kinney HC. (1994) A perspective on neuropathologic findings in victims of the sudden infant death syndrome: The triple risk model. Biology of the Neonate 65: 194-197.
Electrophysiology Study
Na+, Ca2+
CO2
Coates EL. (2001) Olfactory CO2 chemoreceptors. Respiration Physiology 129: 219-229. 1 sec
Immature neuron Na+, Ca2+
Basement membrane
Axons
EOG Amplitude (% max baseline)
Specifically, we sought to determine the role of intracellular and extracellular carbonic anhydrase (CA)
CO2
References
Period 2
Electrophysiology Study
ATP
Period 2
Day 3 (8% CO2)
0% CO2
Period 1
Period 1
Pre-CO2
0% CO2
• Mice exhibited an age-related increase in ventilation with increasing CO2 concentrations.
120
Before - Acetazolamide After - Acetazolamide
N=7
120
100
100
80
80
60
60
40
40
20
20
0
0
0
5
10 15 20 25 30 35 40 45 50
% CO2
Before - QAS After - QAS
Hunt CE, Hauck FR. (2006) Sudden infant death syndrome. Canadian Medical Association Journal 174: 1861-1869. National Institute of Health (2008) www.NIH.gov
N=6
Acknowledgements We thank Dr. and Mrs. Edward Shanbrom for generously funding this project. 0
5
10 15 20 25 30 35 40 45 50
% CO2
