Biology subjects

Karlen-Amarante, M.

Publications and source records attributed to Karlen-Amarante, M..

4 recordsLinked to original sources

bioRxiv2025

Prenatal cannabinoid exposure affects central cardiorespiratory control in young male and female rats

Cannabis use among pregnant women is rising globally, mainly for recreational and medical reasons to relieve symptoms like nausea, vomiting, anxiety, and insomnia. This trend is reinforced by the misconception that its natural origin guarantees safety, along with government policies promoting legalization. However, exposure to cannabinoids in utero can impact normal offsprings neurodevelopment and induce malfunctioning of various physiological systems, including the cardiorespiratory function. The present study investigated whether prenatal cannabinoid exposure disrupts the generation and control of autonomic and respiratory activities in early adulthood. Using in situ preparations of juvenile male and female rats (27-28 days old) exposed to a synthetic cannabinoid (WIN 55,212-2; 0.5 mg/kg/day, n=4-9) or vehicle (n=3-10) during gestation, we analyzed the activity of nerves innervating respiratory muscles and blood vessels. We noticed that females receiving WIN prenatally exhibited a reduced excitatory drive (post-inspiratory activity, post-I) to laryngeal muscles under resting conditions, suggesting impaired control of upper airway patency. Moreover, males and females exposed to WIN displayed reduced post-I and abdominal expiratory motor activities during stimulation of carotid body chemoreceptors (mimicking low oxygen situations) or exposure to high carbon dioxide levels, indicating an inability to mount appropriate reflex respiratory motor responses during blood gas disturbances. In addition, WIN-treated males showed attenuated sympathoexcitatory responses to carotid body activation or hypercapnia, evidencing a limited capacity to promote sympathetic-mediated hemodynamic changes. Thus, manipulating the fetal endocannabinoid system impacts the development of networks controlling respiratory and autonomic functions, leading to negative, long-term consequences for ventilation and cardiovascular function.

physiology↗

bioRxiv2024

Ndufs4 inactivation in glutamatergic neurons reveals swallow-breathing discoordination in a mouse model of Leigh Syndrome

Swallowing, both nutritive and non-nutritive, is highly dysfunctional in children with Leigh Syndrome (LS) and contributes to the need for both gastrostomy and tracheostomy tube placement. Without these interventions aspiration of food, liquid, and mucus occur resulting in repeated bouts of respiratory infection. No study has investigated whether mouse models of LS, a neurometabolic disorder, exhibit dysfunctions in neuromuscular activity of swallow and breathing integration. We used a genetic mouse model of LS in which the NDUFS4 gene is knocked out (KO) specifically in Vglut2 or Gad2 neurons. We found increased variability of the swallow motor pattern, disruption in breathing regeneration post swallow, and water-induced apneas only in Vglut2 KO mice. These physiological changes likely contribute to weight loss and premature death seen in this mouse model. Following chronic hypoxia (CH) exposure, swallow motor pattern, breathing regeneration, weight, and life expectancy were not changed in the Vglut2-Ndufs4-KO CH mice compared to control, indicating a rescue of phenotypes. These findings show that like patients with LS, Ndufs4 mouse models of LS exhibit swallow impairments as well as swallow-breathing dyscoordination alongside the other phenotypic traits described in previous studies. Understanding this aspect of LS will open roads for the development of future more efficacious therapeutic intervention for this illness.

neuroscience↗

bioRxiv2023

Chronic Intermittent Hypoxia reveals role of the Postinspiratory Complex in swallow pattern generation

Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBotzinger Complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.

neuroscience↗

bioRxiv2019

Inhibitory control of active expiration by the Botzinger complex in rats

The expiratory neurons of the Botzinger complex (BotC) provide inhibitory inputs to the respiratory network, which, during eupnea, are critically important for respiratory phase transition and duration control. Herein, we investigated how the BotC neurons interact with the expiratory oscillator located in the parafacial respiratory group (pFRG) and control the abdominal activity during active expiration. Using the decerebrated, arterially perfused in situ rat preparations, we recorded the neuronal activity and performed pharmacological manipulations of the BotC and pFRG during hypercapnia or after the exposure to short-term sustained hypoxia - conditions that generate active expiration. The experimental data were integrated in a mathematical model to gain new insights in the inhibitory connectome within the respiratory central pattern generator. Our results reveal a complex inhibitory circuitry within the BotC that provides inhibitory inputs to the pFRG thus restraining abdominal activity under resting conditions and contributing to abdominal expiratory pattern formation during active expiration.

physiology↗