分类： 生物学 >> 生物医药 提交时间： 2017-03-30
摘要： Mammalian vocalizations require the precise coordination of separate laryngeal and respiratory motor pathways. Precisely how and where in the brain vocal motor patterns interact with respiratory rhythm control is unknown. The parabrachial nucleus (PB) is known to mediate key respiratory reflexes and is also considered a principle component of the mammalian vocal motor pathway, making it a likely site for vocal–respiratory interactions, yet a specific role for the PB in vocalizing has yet to be demonstrated. To investigate the role of the PB in vocal–respiratory coordination, we pharmacologically manipulated synaptic activity in the PB while spontaneously vocalizing horseshoe bats were provoked to emit either short, single syllable or long, multisyllabic vocal motor patterns. Iontophoresis of theGABAA agonist muscimol (MUS) into the lateral PB extended expiratory durations surrounding all vocalizations and increased mean call durations. Alternatively, application of the GABAA antagonist bicuculline methiodide (BIC) shortened expirations and call durations. In addition, BIC eliminated the occurrence of multisyllabic vocalizations. BIC caused a mild increase in quiet breathing rates, whereasMUS tended to slow quiet breathing. The results indicate thatGABAA receptor-mediated inhibition in the lateral PB modulates the time course of respiratory phase switching during vocalizing, and is needed for proper coordination of calling and breathing in mammals. We hypothesize that vocal–respiratory rhythm entrainment is achieved at least in part via mechanisms similar to other forms of locomotorrespiratory coupling, namely somatosensory feedback influences on respiratory phase-switching in the lateral PB.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-05
Wu, R.
Chen, H.
Ma, J.
He, Q.
Yuan, Z.
Wu, R.
Ma, J.
He, Q.
Yuan, Z.
Chen, H.
Yuan, Z.
Huang, Q.
Li, M.
Huang, Q.
Li, M.
Liu, Q.
摘要： Oxidative stress is a major cause of sporadic Parkinson's disease (PD). Here, we demonstrated that c-Abl plays an important role in oxidative stress-induced neuronal cell death. C-Abl, a nonreceptor tyrosine kinase, was activated in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced acute PD model. Conditional knockout of c-Abl in neurons or treatment of mice with STI571, a c-Abl family kinase inhibitor, reduced the loss of dopaminergic neurons and ameliorated the locomotive defects induced by short-term MPTP treatment. By combining the SILAC (stable isotope labeling with amino acids in cell culture) technique with other biochemical methods, we identified p38 alpha as a major substrate of c-Abl both in vitro and in vivo and c-Abl-mediated phosphorylation is critical for the dimerization of p38 alpha. Furthermore, p38 alpha inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38 alpha signaling may represent a therapeutic target for PD.
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