RESUMEN
Nanoparticles (NPs) possess unique properties that make their use valuable in all industries. Titanium dioxide (TiO2) NPs are extensively used as a white pigment in food (labeled under the European number E171) and personal care products, which creates a significant potential for chronic consumer exposure. Concerns about the potential toxic effects of TiO2 NPs have arisen, particularly in vulnerable populations, including pregnant women and infants. Recently, human materno-fetal transfer of E171 was demonstrated, and simultaneously, we reported that chronic prenatal exposure to reference P25 TiO2 NPs was found to alter the developing respiratory neural networks. In this study, using whole body plethysmography from postnatal day (P) 0 to P7, we assessed the respiratory function of newborn mice born to mothers fed with E171 during pregnancy. We also evaluated the potential alterations to respiratory centers by using brainstem-spinal cord electrophysiological recordings from P0 to P6. Our study reveals that E171-prenatally exposed animals displayed an abnormally elevated breathing rate from P3 onwards. From P5 to P6, the respiratory-related burst frequency generated by the isolated brainstem-spinal cord preparations was significantly higher in E171-exposed animals than in non-exposed animals. These findings demonstrate prenatal toxicity of E171 to the developing respiratory function and may contribute to policy-making regarding the use of TiO2 NPs.
RESUMEN
Central motor rhythm-generating networks controlling different functions are generally considered to operate mostly independently from one another, each controlling the specific behavioral task to which it is assigned. However, under certain physiological circumstances, central pattern generators (CPGs) can exhibit strong uni- or bidirectional interactions that render them closely inter-dependent. One of the best illustrations of such an inter-CPG interaction is the functional relationship that may occur between rhythmic locomotor and respiratory functions. It is well known that in vertebrates, lung ventilatory rates accelerate at the onset of physical exercise in order to satisfy the accompanying rapid increase in metabolism. Part of this acceleration is sustained by a coupling between locomotion and ventilation, which most often results in a periodic drive of the respiratory cycle by the locomotor rhythm. In terrestrial vertebrates, the likely physiological significance of this coordination is that it serves to reduce the mechanical interference between the two motor systems, thereby producing an energetic benefit and ultimately, enabling sustained aerobic activity. Several decades of studies have shown that locomotor-respiratory coupling is present in most species, independent of the mode of locomotion employed. The present article aims to review and discuss mechanisms engaged in shaping locomotor-respiratory coupling (LRC), with an emphasis on the role of sensory feedback inputs, the direct influences between CPG networks themselves, and finally on spinal cellular candidates that are potentially involved in the coupling of these two vital motor functions.
RESUMEN
BACKGROUND: Over the last two decades, nanotechnologies and the use of nanoparticles represent one of the greatest technological advances in many fields of human activity. Particles of titanium dioxide (TiO2) are one of the nanomaterials most frequently found in everyday consumer products. But, due in particular to their extremely small size, TiO2 nanoparticles (NPs) are prone to cross biological barriers and potentially lead to adverse health effects. The presence of TiO2 NPs found in human placentae and in the infant meconium has indicated unequivocally the capacity for a materno-fetal transfer of this nanomaterial. Although chronic exposure to TiO2 NPs during pregnancy is known to induce offspring cognitive deficits associated with neurotoxicity, the impact of a gestational exposure on a vital motor function such as respiration, whose functional emergence occurs during fetal development, remains unknown. RESULTS: Using in vivo whole-body plethysmographic recordings from neonatal mice, we show that a chronic exposure to TiO2 NPs during pregnancy alters the respiratory activity of offspring, characterized by an abnormally elevated rate of breathing. Correspondingly, using ex vivo electrophysiological recordings performed on isolated brainstem-spinal cord preparations of newborn mice and medullary slice preparations containing specific nuclei controlling breathing frequency, we show that the spontaneously generated respiratory-related rhythm is significantly and abnormally accelerated in animals prenatally exposed to TiO2 NPs. Moreover, such a chronic prenatal exposure was found to impair the capacity of respiratory neural circuitry to effectively adjust breathing rates in response to excitatory environmental stimuli such as an increase in ambient temperature. CONCLUSIONS: Our findings thus demonstrate that a maternal exposure to TiO2 NPs during pregnancy affects the normal development and operation of the respiratory centers in progeny.
Asunto(s)
Nanopartículas del Metal , Nanopartículas , Animales , Femenino , Humanos , Exposición Materna/efectos adversos , Nanopartículas del Metal/toxicidad , Ratones , Nanopartículas/toxicidad , Embarazo , Respiración , Titanio/toxicidadRESUMEN
Early at the onset of exercise, breathing rate accelerates in order to anticipate the increasing metabolic demand resulting from the extra effort produced. Accordingly, the respiratory neural networks are the target of various input signals originating either centrally or peripherally. For example, during locomotion, the activation of muscle sensory afferents is able to entrain and thereby increase the frequency of spontaneous respiratory rhythmogenesis. Moreover, the lumbar spinal networks engaged in generating hindlimb locomotor rhythms are also capable of activating the medullary respiratory generators through an ascending excitatory command. However, in the context of quadrupedal locomotion, the influence of other spinal cord regions, such as cervical and thoracic segments, remains unknown. Using isolated brainstem-spinal cord preparations from neonatal rats and mice, we show that cervicothoracic circuitry may also contribute to locomotion-induced acceleration of respiratory cycle frequency. As previously observed for the hindlimb CPGs, the pharmacological activation of forelimb locomotor networks produces episodes of fictive locomotion that in turn increase the ongoing respiratory rhythm. Thoracic neuronal circuitry may also participate indirectly in this modulation via the activation of both cervical and lumbar CPG neurons. Furthermore, using light stimulation of CHR2-expressing glutamatergic neurons, we found that the modulation of the respiratory rate during locomotion involves lumbar glutamatergic circuitry. Our results demonstrate that during locomotion, the respiratory rhythm-generating networks receive excitatory ascending inputs from the spinal circuits responsible for generating and coordinating fore- and hindlimb movements. This constitutes a distributed central mechanism that contributes to matching breathing rate to the speed of locomotion.