Max Shao - Academia.edu (original) (raw)

Papers by Max Shao

Research paper thumbnail of Inspiratory rhythmogenic activity is burst-independent and opioid-sensitive

SummaryHow mammalian neural circuits generate rhythmic activity in motor behaviors, such as breat... more SummaryHow mammalian neural circuits generate rhythmic activity in motor behaviors, such as breathing, walking, and chewing, remains elusive. For breathing, rhythm generation can be localized to a brainstem nucleus called the preBötzinger Complex (preBötC). Rhythmic preBötC population activity consists of small amplitude burstlets, which we hypothesize are rhythmogenic, and larger inspiratory bursts, which drive motoneuronal activity. If burstlets are rhythmogenic, opioids, analgesics that can cause profound respiratory depression, should similarly reduce burstlet frequency. In conditions where burstlets were separated from bursts in medullary slices from neonatal mice, the μ-opioid receptor (μOR) agonist DAMGO decreased burstlet frequency. DAMGO-mediated depression was abolished by genetic deletion of μORs in a glutamatergic preBötC subpopulation and was reduced by Substance P, but not blockade of inhibitory synaptic transmission. Our findings suggest that rhythmogenesis need not r...

Research paper thumbnail of Pharmacology of Nicotinic Receptors in PreBötzinger Complex That Mediate Modulation of Respiratory Pattern

Journal of Neurophysiology, Oct 1, 2002

Research paper thumbnail of Chronic intermittent nicotine delivery with lung alveolar region-targeted aerosol technology produces circadian blood pharmacokinetics in rats resembling human smokers

Research paper thumbnail of Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBötzinger Complex Inspiratory Neurons

Journal of Neurophysiology, Mar 1, 2000

Research paper thumbnail of Flavonoids isolated from Tibetan medicines, binding to GABAA receptor and the anticonvulsant activity

Phytomedicine, Nov 1, 2018

Research paper thumbnail of Dihydromyricetin Ameliorates Behavioral Deficits and Reverses Neuropathology of Transgenic Mouse Models of Alzheimer’s Disease

Neurochemical Research, Apr 13, 2014

Research paper thumbnail of Dihydromyricetin As a Novel Anti-Alcohol Intoxication Medication

The Journal of Neuroscience, Jan 4, 2012

Research paper thumbnail of Electronic Cigarette Use and the Risk of Cardiovascular Diseases

Frontiers in Cardiovascular Medicine

Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolesce... more Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolescents. Despite the widespread use of e-cigarettes and the known detrimental cardiac consequences of nicotine, the effects of e-cigarettes on the cardiovascular system are not well-known. Severalin vitroandin vivostudies delineating the mechanisms of the impact of e-cigarettes on the cardiovascular system have been published. These include mechanisms associated with nicotine or other components of the aerosol or thermal degradation products of e-cigarettes. The increased hyperlipidemia, sympathetic dominance, endothelial dysfunction, DNA damage, and macrophage activation are prominent effects of e-cigarettes. Additionally, oxidative stress and inflammation are unifying mechanisms at many levels of the cardiovascular impairment induced by e-cigarette exposure. This review outlines the contribution of e-cigarettes in the development of cardiovascular diseases and their molecular underpinnings.

Research paper thumbnail of Reprogramming of miR-181a/DNA methylation patterns contribute to the maternal nicotine exposure-induced fetal programming of cardiac ischemia-sensitive phenotype in postnatal life

Research paper thumbnail of Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves Anxiety

Frontiers in Pharmacology, 2020

Research paper thumbnail of Author response: Opioids modulate an emergent rhythmogenic process to depress breathing

Research paper thumbnail of Pod-mod vs. conventional e-cigarettes: nicotine chemistry, pH, and health effects

Journal of Applied Physiology, 2019

Research paper thumbnail of A mouse model for chronic intermittent electronic cigarette exposure exhibits nicotine pharmacokinetics resembling human vapers

Journal of Neuroscience Methods, 2019

Research paper thumbnail of Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice

American Journal of Physiology-Heart and Circulatory Physiology, 2019

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a p... more Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE−/−) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE−/− mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractiona...

Research paper thumbnail of Hepatic DNA Damage Induced by Electronic Cigarette Exposure Is Associated With the Modulation of NAD+/PARP1/SIRT1 Axis

Frontiers in Endocrinology, 2019

Research paper thumbnail of RT-PCR reveals muscarinic acetylcholine receptor mRNA in the pre-Bötzinger complex

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2001

Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspir... more Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspiratory neurons in the pre-Bötzinger complex (pre-BötC), the hypothesized site for respiratory rhythm generation. Because pharmacological tools for identifying the subtypes of the muscarinic receptors that underlie these effects are limited, we probed for mRNA for these receptors in the pre-BötC. We used RT-PCR to determine the expression of muscarinic receptor subtypes in tissue punches of the pre-BötC taken from rat medullary slices. Cholinergic receptor subtype M2 and M3 mRNAs were observed in the first round of PCR amplification. All five subtypes, M1–M5, were observed in the second round of amplification. Our results suggest that the majority of muscarinic receptor subtypes in the pre-BötC are M2 and M3, with minor expression of M1, M4, and M5.

Research paper thumbnail of E‐cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases

Hepatology, 2019

The use of electronic nicotine delivery systems (ENDS), also known as e‐cigarettes, with a variet... more The use of electronic nicotine delivery systems (ENDS), also known as e‐cigarettes, with a variety of e‐liquids/e‐juices, is increasing at an alarming rate among adolescents who do not realize the potential harmful health effects. This study examines the harmful effects of ENDS on the liver. Apolipoprotein E null (ApoE‐/‐) mice on a western diet (WD) were exposed to saline or ENDS with 2.4% nicotine aerosol for 12 weeks using our mouse ENDS exposure model system, which delivers nicotine to mice and leads to equivalent serum cotinine levels found in human cigarette users. ApoE‐/‐ mice on a WD exposed to ENDS exhibited a marked increase in hepatic lipid accumulation compared with ApoE‐/‐ on a similar diet exposed to saline aerosol. The detrimental effects of ENDS on hepatic steatosis were associated with significantly greater oxidative stress, increased hepatic triglyceride levels, and increased hepatocyte apoptosis, independent of adenosine monophosphate–activated protein kinase sign...

Research paper thumbnail of Mechanisms Underlying Regulation of Respiratory Pattern by Nicotine in PreBötzinger Complex

Journal of Neurophysiology, 2001

Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from ci... more Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from cigarette smoke affects respiration and is a risk factor for sudden infant death syndrome (SIDS) and sleep-disordered breathing. The cellular and synaptic mechanisms underlying this regulation are not understood. Using a medullary slice preparation from neonatal rat that contains the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythm generation, and generates respiratory-related rhythm in vitro, we examined the effects of nicotine on excitatory neurotransmission affecting inspiratory neurons in preBötC and on the respiratory-related motor activity from hypoglossal nerve (XIIn). Microinjection of nicotine into preBötC increased respiratory frequency and decreased the amplitude of inspiratory bursts, whereas when injected into XII nucleus induced a tonic activity and an increase in amplitude but not in frequency of inspiratory bursts from XIIn. Bath application of n...

Research paper thumbnail of Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers

Journal of Applied Physiology, 2018

Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveola... more Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the par...

Research paper thumbnail of Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBötzinger Complex Inspiratory Neurons

Journal of Neurophysiology, 2000

Perturbations of cholinergic neurotransmission in the brain stem affect respiratory motor pattern... more Perturbations of cholinergic neurotransmission in the brain stem affect respiratory motor pattern both in vivo and in vitro; the underlying cellular mechanisms are unclear. Using a medullary slice preparation from neonatal rat that spontaneously generates respiratory rhythm, we patch-clamped inspiratory neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, and simultaneously recorded respiratory-related motor output from the hypoglossal nerve (XIIn). Most (88%) of the inspiratory neurons tested responded to local application of acetylcholine (ACh) or carbachol (CCh) or bath application of muscarine. Bath application of 50 μM muscarine increased the frequency, amplitude, and duration of XIIn inspiratory bursts. At the cellular level, muscarine induced a tonic inward current, increased the duration, and decreased the amplitude of the phasic inspiratory inward currents in preBötC inspiratory neurons recorded under voltage clamp at −60 m...

Research paper thumbnail of Inspiratory rhythmogenic activity is burst-independent and opioid-sensitive

SummaryHow mammalian neural circuits generate rhythmic activity in motor behaviors, such as breat... more SummaryHow mammalian neural circuits generate rhythmic activity in motor behaviors, such as breathing, walking, and chewing, remains elusive. For breathing, rhythm generation can be localized to a brainstem nucleus called the preBötzinger Complex (preBötC). Rhythmic preBötC population activity consists of small amplitude burstlets, which we hypothesize are rhythmogenic, and larger inspiratory bursts, which drive motoneuronal activity. If burstlets are rhythmogenic, opioids, analgesics that can cause profound respiratory depression, should similarly reduce burstlet frequency. In conditions where burstlets were separated from bursts in medullary slices from neonatal mice, the μ-opioid receptor (μOR) agonist DAMGO decreased burstlet frequency. DAMGO-mediated depression was abolished by genetic deletion of μORs in a glutamatergic preBötC subpopulation and was reduced by Substance P, but not blockade of inhibitory synaptic transmission. Our findings suggest that rhythmogenesis need not r...

Research paper thumbnail of Pharmacology of Nicotinic Receptors in PreBötzinger Complex That Mediate Modulation of Respiratory Pattern

Journal of Neurophysiology, Oct 1, 2002

Research paper thumbnail of Chronic intermittent nicotine delivery with lung alveolar region-targeted aerosol technology produces circadian blood pharmacokinetics in rats resembling human smokers

Research paper thumbnail of Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBötzinger Complex Inspiratory Neurons

Journal of Neurophysiology, Mar 1, 2000

Research paper thumbnail of Flavonoids isolated from Tibetan medicines, binding to GABAA receptor and the anticonvulsant activity

Phytomedicine, Nov 1, 2018

Research paper thumbnail of Dihydromyricetin Ameliorates Behavioral Deficits and Reverses Neuropathology of Transgenic Mouse Models of Alzheimer’s Disease

Neurochemical Research, Apr 13, 2014

Research paper thumbnail of Dihydromyricetin As a Novel Anti-Alcohol Intoxication Medication

The Journal of Neuroscience, Jan 4, 2012

Research paper thumbnail of Electronic Cigarette Use and the Risk of Cardiovascular Diseases

Frontiers in Cardiovascular Medicine

Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolesce... more Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolescents. Despite the widespread use of e-cigarettes and the known detrimental cardiac consequences of nicotine, the effects of e-cigarettes on the cardiovascular system are not well-known. Severalin vitroandin vivostudies delineating the mechanisms of the impact of e-cigarettes on the cardiovascular system have been published. These include mechanisms associated with nicotine or other components of the aerosol or thermal degradation products of e-cigarettes. The increased hyperlipidemia, sympathetic dominance, endothelial dysfunction, DNA damage, and macrophage activation are prominent effects of e-cigarettes. Additionally, oxidative stress and inflammation are unifying mechanisms at many levels of the cardiovascular impairment induced by e-cigarette exposure. This review outlines the contribution of e-cigarettes in the development of cardiovascular diseases and their molecular underpinnings.

Research paper thumbnail of Reprogramming of miR-181a/DNA methylation patterns contribute to the maternal nicotine exposure-induced fetal programming of cardiac ischemia-sensitive phenotype in postnatal life

Research paper thumbnail of Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves Anxiety

Frontiers in Pharmacology, 2020

Research paper thumbnail of Author response: Opioids modulate an emergent rhythmogenic process to depress breathing

Research paper thumbnail of Pod-mod vs. conventional e-cigarettes: nicotine chemistry, pH, and health effects

Journal of Applied Physiology, 2019

Research paper thumbnail of A mouse model for chronic intermittent electronic cigarette exposure exhibits nicotine pharmacokinetics resembling human vapers

Journal of Neuroscience Methods, 2019

Research paper thumbnail of Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice

American Journal of Physiology-Heart and Circulatory Physiology, 2019

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a p... more Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE−/−) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE−/− mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractiona...

Research paper thumbnail of Hepatic DNA Damage Induced by Electronic Cigarette Exposure Is Associated With the Modulation of NAD+/PARP1/SIRT1 Axis

Frontiers in Endocrinology, 2019

Research paper thumbnail of RT-PCR reveals muscarinic acetylcholine receptor mRNA in the pre-Bötzinger complex

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2001

Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspir... more Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspiratory neurons in the pre-Bötzinger complex (pre-BötC), the hypothesized site for respiratory rhythm generation. Because pharmacological tools for identifying the subtypes of the muscarinic receptors that underlie these effects are limited, we probed for mRNA for these receptors in the pre-BötC. We used RT-PCR to determine the expression of muscarinic receptor subtypes in tissue punches of the pre-BötC taken from rat medullary slices. Cholinergic receptor subtype M2 and M3 mRNAs were observed in the first round of PCR amplification. All five subtypes, M1–M5, were observed in the second round of amplification. Our results suggest that the majority of muscarinic receptor subtypes in the pre-BötC are M2 and M3, with minor expression of M1, M4, and M5.

Research paper thumbnail of E‐cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases

Hepatology, 2019

The use of electronic nicotine delivery systems (ENDS), also known as e‐cigarettes, with a variet... more The use of electronic nicotine delivery systems (ENDS), also known as e‐cigarettes, with a variety of e‐liquids/e‐juices, is increasing at an alarming rate among adolescents who do not realize the potential harmful health effects. This study examines the harmful effects of ENDS on the liver. Apolipoprotein E null (ApoE‐/‐) mice on a western diet (WD) were exposed to saline or ENDS with 2.4% nicotine aerosol for 12 weeks using our mouse ENDS exposure model system, which delivers nicotine to mice and leads to equivalent serum cotinine levels found in human cigarette users. ApoE‐/‐ mice on a WD exposed to ENDS exhibited a marked increase in hepatic lipid accumulation compared with ApoE‐/‐ on a similar diet exposed to saline aerosol. The detrimental effects of ENDS on hepatic steatosis were associated with significantly greater oxidative stress, increased hepatic triglyceride levels, and increased hepatocyte apoptosis, independent of adenosine monophosphate–activated protein kinase sign...

Research paper thumbnail of Mechanisms Underlying Regulation of Respiratory Pattern by Nicotine in PreBötzinger Complex

Journal of Neurophysiology, 2001

Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from ci... more Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from cigarette smoke affects respiration and is a risk factor for sudden infant death syndrome (SIDS) and sleep-disordered breathing. The cellular and synaptic mechanisms underlying this regulation are not understood. Using a medullary slice preparation from neonatal rat that contains the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythm generation, and generates respiratory-related rhythm in vitro, we examined the effects of nicotine on excitatory neurotransmission affecting inspiratory neurons in preBötC and on the respiratory-related motor activity from hypoglossal nerve (XIIn). Microinjection of nicotine into preBötC increased respiratory frequency and decreased the amplitude of inspiratory bursts, whereas when injected into XII nucleus induced a tonic activity and an increase in amplitude but not in frequency of inspiratory bursts from XIIn. Bath application of n...

Research paper thumbnail of Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers

Journal of Applied Physiology, 2018

Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveola... more Cigarette smoke is an aerosol containing microparticles that carry nicotine into the lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with episodic intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. We developed an integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method. We characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet-size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. Rats were exposed to nicotine aerosol once every half hour in the dark phase of 12:12-h light-dark cycles for 10 days. We optimized the par...

Research paper thumbnail of Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBötzinger Complex Inspiratory Neurons

Journal of Neurophysiology, 2000

Perturbations of cholinergic neurotransmission in the brain stem affect respiratory motor pattern... more Perturbations of cholinergic neurotransmission in the brain stem affect respiratory motor pattern both in vivo and in vitro; the underlying cellular mechanisms are unclear. Using a medullary slice preparation from neonatal rat that spontaneously generates respiratory rhythm, we patch-clamped inspiratory neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, and simultaneously recorded respiratory-related motor output from the hypoglossal nerve (XIIn). Most (88%) of the inspiratory neurons tested responded to local application of acetylcholine (ACh) or carbachol (CCh) or bath application of muscarine. Bath application of 50 μM muscarine increased the frequency, amplitude, and duration of XIIn inspiratory bursts. At the cellular level, muscarine induced a tonic inward current, increased the duration, and decreased the amplitude of the phasic inspiratory inward currents in preBötC inspiratory neurons recorded under voltage clamp at −60 m...