Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: Partial protection by acute minocycline

Maternal opioids age-dependently impair neonatal respiratory control networks

“…In contrast, burst amplitudes after mu-opioid receptor antagonism increased from baseline in P0-1 neonates after maternal opioids (14% ± 6% change from baseline, p = 0.03), while burst amplitude from older neonates after maternal opioids were unchanged from baseline (P2 neonates after maternal opioids = −10% ± 6% change from baseline, p = 0.09; P3-5 neonates after maternal opioids = −12% ± 4% change from baseline, p = 0.07). The decrease in burst frequency and amplitude in neonates after maternal no treatment is consistent with previous studies using in vitro electrophysiology to study the respiratory network activity ( Alvares et al, 2014 ; Blitz and Ramirez, 2002 ; Camacho-Hernández et al, 2022 ; Johnson et al, 2012 ), reflecting typical changes in activity over time. Thus, lingering neonatal opioids may contribute to acute changes in burst amplitude, but not frequency, in neonates after maternal opioids.…”

“…Our results demonstrating maternal opioids decrease respiratory burst amplitude and emergence of a distinct respiratory pattern at all ages provide support for the hypothesis that maternal opioids disrupt perinatal maturation of central respiratory networks. Many early life stressors, such as gestational intermittent hypoxia ( Gozal et al, 2003 ; Johnson et al, 2017 ), gestational ethanol exposure ( Dubois and Pierrefiche, 2020 ), prenatal anxiety drug exposure ( da Silva Junior et al, 2022 ), perinatal inflammation ( Morrison et al, 2019 ; Camacho-Hernández et al, 2022 ), perinatal nicotine exposure ( Luo et al, 2004 ; Ferng and Fregosi, 2015 ; Cholanian et al, 2017 ), perinatal anti-depressant drug exposure ( Biancardi et al, 2022 ) and neonatal maternal separation ( Kinkead et al, 2005 ; Kinkead and Gulemetova, 2010 ; Rousseau et al, 2017 ; reviewed in Tenorio-Lopes and Kinkead, 2021 ), acutely disrupt neonatal respiratory control. Some of these stressors even have enduring consequences on the adult respiratory system ( Genest et al, 2004 ; Kinkead et al, 2009 ; Soliz et al, 2016 ; Hocker et al, 2019 ; Dubois and Pierrefiche, 2020 ; Biancardi et al, 2022 ).…”

Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease

“…A vital function that is highly sensitive to inflammation and microglial modulation is breathing [189,190,216,217], which is generated by the pre-Bötzinger complex (preBötC) [218][219][220] and can be maintained in a brainstem slice preparation [189,190,217,220,221]. The preBötC and its motor outputs can adapt their function upon changes in oxygen supply [189,190,217,[219][220][221] and can induce long-term facilitation (LTF) in their activity in response to acute intermittent hypoxia (AIH) [190,217,219]. LTF is a form of respiratory plasticity that consists in a long-term increase in inspiratory frequency and/or amplitude evoked by stimulation of respiratory peripheral nerves or AIH [190,217,219].…”

“…The preBötC and its motor outputs can adapt their function upon changes in oxygen supply [189,190,217,[219][220][221] and can induce long-term facilitation (LTF) in their activity in response to acute intermittent hypoxia (AIH) [190,217,219]. LTF is a form of respiratory plasticity that consists in a long-term increase in inspiratory frequency and/or amplitude evoked by stimulation of respiratory peripheral nerves or AIH [190,217,219]. LTF is dependent on both BDNF [222] and adenosine [223].…”

“…LTF is dependent on both BDNF [ 222 ] and adenosine [ 223 ]. This plastic change is highly sensitive to microglial modulation [ 190 , 217 ]. For instance, we have shown that LTF is blocked after microglia depletion and LPS administration in vitro [ 190 ].…”