Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.
Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.
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TG(TH-CRE)FI172GSAT(TH-CRE)定义了全超含量和低氧反射所需的神经元。
DOI:
10.1242/bio.026823
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发表时间:
2017-08-15
期刊:
影响因子:
2.4
通讯作者:
Ray RS
中科院分区:
文献类型:
--
作者:
Sun JJ;Ray RS
The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat (Th-Cre)-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREADD-mediated inhibition of Th-Cre-defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5% CO2/21% O2/74% N2), perturbation of Th-Cre neurons results in reduced fR, and . Under a hypoxic challenge (10% O2/90% N2), we saw reduced fR, and , in addition to instability in both interbreath interval and tidal volume, resulting in a Cheyne-Stokes-like respiratory pattern. These findings demonstrate the necessity of Th-Cre-defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-CA expression domains of the Tg(Th-Cre)FI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to CA neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges. Summary: DREADD-mediated silencing of Tg(Th-Cre)FI172Gsat-defined neurons in adult mice results in reduced O2 and CO2 breathing reflexes and respiratory rhythm destabilization under hypoxic challenge, resembling Cheyne-Stokes respiration.
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影响因子:
3.4
作者:
Hakim F;Gozal D;Kheirandish-Gozal L
通讯作者:
Kheirandish-Gozal L
DOI:
10.1126/science.1205295
发表时间:
2011-07-29
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
Ray RS;Corcoran AE;Brust RD;Kim JC;Richerson GB;Nattie E;Dymecki SM
通讯作者:
Dymecki SM
影响因子:
5.5
作者:
Cummings, KJ;Pendlebury, JD;Wilson, RJA
通讯作者:
Wilson, RJA
DOI:
10.1073/pnas.0906593106
发表时间:
2009-11-10
影响因子:
11.1
作者:
Guettier, Jean-Marc;Gautam, Dinesh;Wess, Juergen
通讯作者:
Wess, Juergen
影响因子:
2.3
作者:
Viemari, Jean-Charles
通讯作者:
Viemari, Jean-Charles