scholarly journals Differential role of type I and type II vestibular hair cells in two anti-gravity reflexes in the rat

2020 ◽  
Author(s):  
Alberto F. Maroto ◽  
Alejandro Barrallo-Gimeno ◽  
Jordi Llorens

AbstractThe tail-lift reflex and the air-righting reflex in rats are anti-gravity reflexes that depend on vestibular function. We assessed reflex loss in relationship to the graded lesions caused in the vestibular sensory epithelia by varying doses of an ototoxic compound. Using high-speed video recording, we obtained nose-back of the neck-tail angles from the tail-lift reflex and time to right in the air-righting test. We then correlated these measures with type I (HCI), type II (HCII) and all hair cell (HC) counts in central and peripheral zones of the crista, utricle, and saccule. Correlations varied with the cell type, zone and end-organ considered, and those of tail-lift angles were strikingly greater with HCI counts that HCII counts. A similar HCI vs HCII difference was not recorded for air-righting times. We conclude that these two reflexes depend differently on HCI and HCII function and that the tail-lift angle measures HCI function.

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 125S-133S ◽  
Author(s):  
Terry J. Prins ◽  
Johnny J. Saldate ◽  
Gerald S. Berke ◽  
Larry F. Hoffman

Objectives: Early in his career, David Lim recognized the scientific impact of genetically anomalous mice exhibiting otoconia agenesis as models of drastically compromised vestibular function. While these studies focused on the mutant pallid mouse, contemporary genetic tools have produced other models with engineered functional modifications. Lim and colleagues foresaw the need to analyze vestibular epithelia from pallid mice to verify the absence of downstream consequences that might be secondary to the altered load represented by otoconial agenesis. More generally, however, such comparisons also contribute to an understanding of the susceptibility of labyrinthine sensory epithelia to more widespread cellular changes associated with what may appear as isolated modifications. Methods: Our laboratory utilizes a model of vestibular hypofunction produced through genetic alteration, the otoferlin-null mouse, which has been shown to exhibit severely compromised stimulus-evoked neurotransmitter release in type I hair cells of the utricular striola. The present study, reminiscent of early investigations of Lim and colleagues that explored the utility of a genetically altered mouse to explore its utility as a model of vestibular hypofunction, endeavored to compare the expression of the hair cell marker oncomodulin in vestibular epithelia from wild-type and otoferlin-null mice. Results: We found that levels of oncomodulin expression were much greater in type I than type II hair cells, though were similar across the 3 genotypes examined (ie, including heterozygotes). Conclusion: These findings support the notion that modifications resulting in a specific component of vestibular hypofunction are not accompanied by widespread morphologic and cellular changes in the vestibular sensory epithelia.


2005 ◽  
Vol 93 (1) ◽  
pp. 251-266 ◽  
Author(s):  
Sapan S. Desai ◽  
Catherine Zeh ◽  
Anna Lysakowski

Calyx afferents, a group of morphologically and physiologically distinct afferent fibers innervating the striolar region of vestibular sensory epithelia, are selectively labeled by antibodies to the calcium-binding protein calretinin. In this study, the population of calretinin-stained calyx afferents was used to delineate and quantify the striolar region in six rodent species: mouse, rat, gerbil, guinea pig, chinchilla, and tree squirrel. Morphometric studies and hair cell and calyx afferent counts were done. Numbers of hair cells, area, length, and width of the sensory epithelium increase from mouse to tree squirrel. In the mouse and rat, calretinin is found in 5–9% of all type I hair cells, 20–40% of striolar type II hair cells, and 70–80% of extrastriolar type II hair cells. Numbers of calyx afferents increase from mouse to squirrel, with more complex calyx afferents in larger species. About 10% of calyx afferents are branched. Based on our counts of total numbers of calyx afferents in chinchilla maculae and in comparison to fiber counts in the literature, the proportion of calyx afferents is greater than previously described, constituting nearly 20% of the total. Because morphometric measures increase with body weight, we obtained additional data on vestibular end organ surface areas from the literature and used this to construct a power law function describing this relationship. The function holds for species with body weights less than ∼4 kg. Greater than 4 kg, the surface area of the sensory epithelia remains constant even with increasing body weight.


2019 ◽  
Author(s):  
Vanessa Martins-Lopes ◽  
Anna Bellmunt ◽  
Erin A. Greguske ◽  
Alberto F. Maroto ◽  
Pere Boadas-Vaello ◽  
...  

AbstractThe tail-lift reflex and the air-righting reflex are anti-gravity reflexes in rats that depend on vestibular function. To obtain objective and quantitative measures of performance, we recorded these reflexes with slow motion video in two experiments. In the first experiment, vestibular dysfunction was elicited by acute exposure to 0 (control), 400, 600 or 1000 mg/kg of 3,3’-iminodipropionitrile (IDPN), which causes dose-dependent hair cell degeneration. In the second, rats were exposed to sub-chronic IDPN in the drinking water for 0 (control), 4 or 8 weeks; this causes reversible or irreversible loss of vestibular function depending on exposure time. In the tail-lift test, we obtained the minimum angle defined during the lift and descent maneuver by the nose, the back of the neck and the base of the tail. In the air-righting test, we obtained the time to right the head. We also obtained Vestibular Dysfunction Ratings (VDRs) using a previously validated behavioral test battery. Each measure, VDR, tail-lift angle and air-righting time, demonstrated dose-dependent loss of vestibular function after acute IDPN, and time-dependent loss of vestibular function after sub-chronic IDPN. All measures showed high correlations between each other, and maximal correlation coefficients were found between VDRs and tail-lift angles. In scanning electron microscopy evaluation of the vestibular sensory epithelia, the utricle and the saccule showed diverse pathological outcomes, suggesting that they have a different role in these reflexes. We conclude that these anti-gravity reflexes provide useful objective and quantitative measures of vestibular function in rats that are open to further development.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1641
Author(s):  
Emily E. S. Brettschneider ◽  
Masaki Terabe

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.


Minerals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 451
Author(s):  
Galina Palyanova ◽  
Valery Murzin ◽  
Andrey Borovikov ◽  
Nikolay Karmanov ◽  
Sergei Kuznetsov

Composition of native gold and minerals in intergrowth with rhyolites of the Chudnoe Au-Pd-REE deposit (Subpolar Urals, Russia) was studied using optical microscopy, scanning electron microscopy, and electron microprobe analysis. Five varieties of native gold have been identified, based on the set of impurity elements and their quantities, and on intergrown minerals. Native gold in rhyolites from the Ludnaya ore zone is homogeneous and contains only Ag (fineness 720‰, type I). It is in intergrowth with fuchsite or allanite and mertieite-II. In rhyolites from the Slavnaya ore zone, native gold is heterogeneous, has a higher fineness, different sets and contents of elements: Ag, Cu, 840–860‰ (type II); Ag, Cu, Pd, 830–890‰ (III); Ag, Pd, Cu, Hg, 840–870‰ (IV). It occurs in intergrowth with fuchsite, albite, and mertieite-II (type II), or albite, quartz, and atheneite (III), or quartz, albite, K-feldspar, and mertieite-II (IV). High fineness gold (930–1000‰, type V) with low contents of Ag, Cu, and Pd or their absence occurs in the form as microveins, fringes and microinclusions in native gold II–IV. Tetra-auricupride (AuCu) is presented as isometric inclusions in gold II and platelets in the decay structures in gold III and IV. The preliminary data of a fluid inclusions study showed that gold mineralization at the Chudnoe deposit could have been formed by chloride fluids of low and medium salinity at temperatures from 105 to 230 °C and pressures from 5 to 115 MPa. The formation of native gold I is probably related to fuchsitization and allanitization of rhyolites. The formation of native gold II-V is also associated with the same processes, but it is more complicated and occurred later with a significant role of Na-, Si-, and K-metasomatism. The presence of Pd and Cu in the ores and Cr in fuchsite indicates the important role of mafic-ultramafic magmatism.


2010 ◽  
Vol 10 ◽  
pp. 2367-2384 ◽  
Author(s):  
Eduardo Pérez-Gómez ◽  
Gaelle del Castillo ◽  
Juan Francisco Santibáñez ◽  
Jose Miguel Lêpez-Novoa ◽  
Carmelo Bernabéu ◽  
...  

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.


1985 ◽  
Vol 248 (3) ◽  
pp. R302-R307 ◽  
Author(s):  
W. W. Winder ◽  
M. L. Terry ◽  
V. M. Mitchell

We have investigated the physiological role of the marked increase in plasma epinephrine that occurs in fasted exercising rats. Fasted adrenodemedullated (ADM) rats show a marked reduction in endurance run times compared with sham-operated (SO) controls. After running for 30 min at 21 m/min up a 10% grade, ADM rats' blood glucose was 2.9 +/- 0.1 mM vs. 4.3 +/- 0.2 mM in SO rats. At the same time, blood lactate was 3.0 +/- 0.2 mM in SO rats compared with 1.0 +/- 0.1 mM in ADM rats. Glycogenolysis was impaired in ADM rats in the fast-twitch white region of the quadriceps, lateral gastrocnemius, and soleus muscles but not in the fast-twitch red region of the quadriceps muscle. Hepatic adenosine 3',-5'-cyclic monophosphate was increased to the same extent in ADM and SO rats during exercise. Infusion of epinephrine into ADM rats during exercise corrected the hypoglycemia, restored lactate to normal, and stimulated glycogenolysis in soleus, white quadriceps, and lateral gastrocnemius muscles. Epinephrine-dependent glycogenolysis in contracting type I and noncontracting type II muscle fibers apparently provides essential quantities of lactate for hepatic gluconeogenesis in fasted exercising rats.


2004 ◽  
Vol 19 (2) ◽  
pp. 155-169 ◽  
Author(s):  
Manning J. Correia ◽  
Thomas G. Wood ◽  
Deborah Prusak ◽  
Tianxiang Weng ◽  
Katherine J. Rennie ◽  
...  

A fast inwardly rectifying current has been observed in some of the sensory cells (hair cells) of the inner ear of several species. While the current was presumed to be an IKir current, contradictory evidence existed as to whether the cloned channel actually belonged to the Kir2.0 subfamily of potassium inward rectifiers. In this paper, we report for the first time converging evidence from electrophysiological, biochemical, immunohistochemical, and genetic studies that show that the Kir2.1 channel carries the fast inwardly rectifying currents found in pigeon vestibular hair cells. Following cytoplasm extraction from single type II and multiple pigeon vestibular hair cells, mRNA was reverse transcribed, amplified, and sequenced. The open reading frame (ORF), consisting of a 1,284-bp nucleotide sequence, showed 94, 85, and 83% identity with Kir2.1 subunit sequences from chick lens, Kir2 sequences from human heart, and a mouse macrophage cell line, respectively. Phylogenetic analyses revealed that pKir2.1 formed an immediate node with hKir2.1 but not with hKir2.2–2.4. Hair cells (type I and type II) and supporting cells in the sensory epithelium reacted positively with a Kir2.1 antibody. The whole cell current recorded in oocytes and CHO cells, transfected with pigeon hair cell Kir2.1 (pKir2.1), demonstrated blockage by Ba2+ and sensitivity to changing K+ concentration. The mean single-channel linear slope conductance in transfected CHO cells was 29 pS. The open dwell time was long (∼300 ms at −100 mV), and the closed dwell time was short (∼34 ms at −100 mV). Multistates ranging from 3–6 were noted in some single-channel responses. All of the above features have been described for other Kir2.1 channels. Current clamp studies of native pigeon vestibular hair cells illustrated possible physiological roles of the channel and showed that blockage of the channel by Ba2+ depolarized the resting membrane potential by ∼30 mV. Negative currents hyperpolarized the membrane ∼20 mV before block but ∼60 mV following block. RT-PCR studies revealed that the pKir2.1 channels found in pigeon vestibular hair cells were also present in pigeon vestibular nerve, vestibular ganglion, lens, neck muscle, brain (brain stem, cerebellum and optic tectum), liver, and heart.


Reproduction ◽  
2002 ◽  
pp. 799-806 ◽  
Author(s):  
KF Rodriguez ◽  
RM Petters ◽  
AE Crosier ◽  
CE Farin

The aims of this study were to examine the role of transcription and the coincident involvement of type I and type II protein kinase A (PKA) in the resumption of meiosis in murine cumulus-oocyte complexes (COCs) using the transcriptional inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) and alpha-amanitin. The first series of experiments was designed to: (i) characterize the role of transcription in gonadotrophin-mediated and spontaneous maturation of murine oocytes; (ii) examine the roles of specific gonadotrophins (FSH versus hCG) and cumulus cells in transcriptionally mediated oocyte maturation; and (iii) determine the reversibility of the transcriptional arrest of meiosis. In the presence of FSH, transcriptional inhibitors arrested germinal vesicle breakdown (GVBD) (DRB: 2 +/- 2% and control: 76 +/- 2%; alpha-amanitin: 4 +/- 4% and control: 70 +/- 4%). Furthermore, cumulus cells were required for transcriptional inhibitors to arrest GVBD (DRB with cumulus cells: 0 +/- 15%; DRB without cumulus cells: 94 +/- 13%; alpha-amanitin with cumulus cells: 15 +/- 2%; alpha-amanitin without cumulus cells: 99 +/- 2%). Thus, in mice, FSH-mediated GVBD uses a transcriptional mechanism, which probably occurs within the cumulus cell compartment. In a second series of experiments, the role of transcription in mediating the resumption of meiosis after activation of either type I or type II PKA was examined. Activation of type I PKA in murine COCs resulted in an arrest of GVBD that was independent of a transcriptional event (with DRB: 7 +/- 9% GVBD; without DRB: 11 +/- 9% GVBD). In contrast, activation of type II PKA resulted in a resumption of meiosis, which required the occurrence of gene transcription (with DRB: 12 +/- 9% GVBD; without DRB: 80 +/- 9% GVBD). As FSH binding to cumulus cells activates the PKA second messenger system, our results indicate that, in cultured murine COCs, FSH binding to cumulus cells results in the activation of type II PKA, which, in turn, mediates a downstream transcriptional event required for the initiation of GVBD.


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