Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice

Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem neurons.Zfhx4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse brainstem.Mice lacking Zfhx4 died shortly after birth from an apparent inability to initiate respiration.We also found that the electrical rhythm of brainstem‒spinal cord preparations was significantly depressed in Zfhx4-null mice compared to wild-type mice.Immunofluorescence staining revealed that Zfhx4 was coexpressed with Phox2b and Math1 in the brainstem and that Zfhx4 ablation greatly decreased the expression of these proteins,especially in the retrotrapezoid nucleus.Combined ChIP‒seq and mRNA expression microarray analysis identified Phox2b as the direct downstream target gene of Zfhx4,and this finding was validated by ChIP‒qPCR.Previous studies have reported that both Phox2b and Math1 play key roles in the development of the respiratory center,and Phox2b and Math1 knockout mice are neonatal lethal due to severe central apnea.On top of this,our study revealed that Zfhx4 is a critical regulator of Phox2b expression and essential for perinatal breathing.

Effect of vocal respiratory training on respiratory function and respiratory neural plasticity in patients with cervical spinal cord injury:a randomized controlled trial

In previous studies,researchers have used singing to treat respiratory function in patients with spinal cord injury.However,few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury.Vocal respiratory training(VRT)is a type of vocal muscle-related treatment that is often a component of music therapy(MT)and focuses on strengthening respiratory muscles and improving lung function.In this randomized controlled study,we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury.Of an initial group of 37 patients,26 completed the music therapy intervention,which comprised five 30-minute sessions per week for 12 weeks.The intervention group(n=13)received VRT training delivered by professional certified music therapists.The control group(n=13)received respiratory physical therapy delivered by professional physical therapists.Compared with the control group,we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention.Further,the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification,with an increased number,path length,thickness,and density of nerve fiber bundles.These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2020-013-1)on April 1,2020,and was registered with the Chinese Clinical Trial Registry(registration No.Chi CTR2000037871)on September 2,2020.

Neurotoxicity of prenatal alcohol exposure on medullary pre-B?tzinger complex neurons in neonatal rats

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.