Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

Zhang, Zhe; Yang, Dong; Zhang, Mengdi; Zhu, Nianyong; Zhou, Yanfen; Storm, Daniel R.; Wang, Zhenshan

doi:10.3389/fncel.2017.00001

Cited by 90 publications

(127 citation statements)

References 77 publications

(102 reference statements)

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“…Interestingly, there is little mention of ototoxicity in horses, which may be a major complication in human patients 23. Recommended target trough concentrations are variable although generally considered to be no higher than 1–2 μg/mL, although little evidence supports this concentration range 9.…”

Section: Discussionmentioning

confidence: 99%

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice

Durham¹

2018

Veterinary Internal Medicne

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BackgroundTherapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.Hypothesis/ObjectivesTo measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected.MethodsRetrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints.ResultsThe median serum gentamicin concentration at 60 minutes after administration (C 60min) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses.Conclusions and Clinical ImportanceGentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study.

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Section: Discussionmentioning

confidence: 99%

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice

Durham¹

2018

Veterinary Internal Medicne

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“…This high [Cl − ] i is maintained by the activity of the isoform 1 of the Na + -dependent K + , Cl − Cotransporter (NKCC1), which mediates an uptake of Cl − 4 – 8 . The depolarizing GABAergic responses in the immature hippocampus have been associated with the generation of spontaneous oscillatory activity transients that are essential for brain development 9 , 10 , but also to the higher incidence and pharmacological refractoriness of epileptic seizures in the immature CNS 11 – 14 .…”

Section: Introductionmentioning

confidence: 99%

NKCC-1 mediated Cl− uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs

Kolbaev

Mohapatra

Chen

et al. 2020

Sci Rep

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Activation of GABAA receptors causes in immature neurons a functionally relevant decrease in the intracellular Cl− concentration ([Cl−]i), a process termed ionic plasticity. Amount and duration of ionic plasticity depends on kinetic properties of [Cl−]i homeostasis. In order to characterize the capacity of Cl− accumulation and to quantify the effect of persistent GABAergic activity on [Cl−]i, we performed gramicidin-perforated patch-clamp recordings from CA3 pyramidal neurons of immature (postnatal day 4–7) rat hippocampal slices. These experiments revealed that inhibition of NKCC1 decreased [Cl−]i toward passive distribution with a time constant of 381 s. In contrast, active Cl− accumulation occurred with a time constant of 155 s, corresponding to a rate of 15.4 µM/s. Inhibition of phasic GABAergic activity had no significant effect on steady state [Cl−]i. Inhibition of tonic GABAergic currents induced a significant [Cl−]i increase by 1.6 mM, while activation of tonic extrasynaptic GABAA receptors with THIP significantly reduced [Cl−]i.. Simulations of neuronal [Cl−]i homeostasis supported the observation, that basal levels of synaptic GABAergic activation do not affect [Cl−]i. In summary, these results indicate that active Cl−-uptake in immature hippocampal neurons is sufficient to maintain stable [Cl−]i at basal levels of phasic and to some extent also to compensate tonic GABAergic activity.

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“…The molecular pathways underlying the crucial functions of glial cells, astrocytes, microglia, and oligodendroglial lineage cells, which were in the past thought to have simply a supportive or “glue” - like function, in both the healthy and diseased central nervous system (CNS), are increasingly being elucidated (Jäkel and Dimou, 2017). Astrocytes have a multitude of essential functions in the CNS (see also above), providing neurotrophic support, promoting formation and maintenance of synaptic activity and transmission, regulating blood flow and determining some functions and properties of the blood-brain barrier (BBB) or neurovascular unit (NVU) (Sofroniew, 2009; Sofroniew and Vinters, 2010).…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…Oligodendroglial lineage cells include oligodendrocytes and the oligodendrocyte precursors, NG2-glia (Jäkel and Dimou, 2017). Although the functions of these NG2 proteoglycan protein expressing glia are still unclear, they generate mature myelinating oligodendrocytes and are able to form functional synapses with neurons (Jäkel and Dimou, 2017; Nave, 2010).…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…Although the functions of these NG2 proteoglycan protein expressing glia are still unclear, they generate mature myelinating oligodendrocytes and are able to form functional synapses with neurons (Jäkel and Dimou, 2017; Nave, 2010). Oligodendrocytes are abundant in the grey and white matter of the brain and spinal cord and produce myelin to insulate CNS axons for rapid saltatory conduction and provide neurotrophic support (Dewar et al, 2003; Jäkel and Dimou, 2017). They contain abundant microtubules for transporting myelin proteins to their processes, and the microtubule associated protein tau.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

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Glial function (and dysfunction) in the normal & ischemic brain

2018

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Astrocytes are the most abundant cell type in the central nervous system (CNS). Once considered to be of fairly homogeneous phenotype throughout the brain and spinal cord, they are now understood to be heterogeneous in both structure and function. They are important in brain functions as diverse as ion and fluid balance in the interstitial space, contributing to integrity of the neurovascular unit (blood-brain barrier), neurotransmitter regulation, metabolism of energy substrates and possibly even axonal regeneration. After ischemic or hemorrhagic brain/spinal cord injury, formation of an astrocytic scar adjacent to the ‘lesion’ is a characteristic histopathologic feature, and this astrogliosis can be demonstrated by immunohistochemistry, usually using primary antibodies to glial fibrillary acidic protein (GFAP). Astrocytes interact with microglia and oligodendroglia in novel ways that will be discussed in this review. This article is part of the Special Issue entitled ‘Cerebral Ischemia’.

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Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

Cited by 90 publications

References 77 publications

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice

NKCC-1 mediated Cl− uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs

Glial function (and dysfunction) in the normal & ischemic brain

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