scholarly journals Spontaneous Calcium Waves in Bergman Glia Increase with Age and Hypoxia and may Reduce Tissue Oxygen

2012 ◽  
Vol 33 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Claus Mathiesen ◽  
Alexey Brazhe ◽  
Kirsten Thomsen ◽  
Martin Lauritzen
Keyword(s):  
Oxygen Tension ◽  
Cerebellar Cortex ◽  
Energy Homeostasis ◽  
Oxygen Metabolism ◽  
Wave Activity ◽  
Blood Oxygen Saturation ◽  
Brain Oxygen ◽  
Adult Mice ◽  
Intracellular Ca

Glial calcium (Ca2+) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca2+ waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O2 tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca2+ activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

scholarly journals Parasagittally aligned, mGluR1-dependent patches are evoked at long latencies by parallel fiber stimulation in the mouse cerebellar cortex in vivo

2011 ◽  
Vol 105 (4) ◽  
pp. 1732-1746 ◽  
Author(s):  
Xinming Wang ◽  
Gang Chen ◽  
Wangcai Gao ◽  
Timothy J. Ebner
Keyword(s):  
Glutamate Receptor ◽  
Cerebellar Cortex ◽  
High Frequency ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
Metabotropic Glutamate ◽  
Zebrin Ii ◽  
Long Latency ◽  
Intracellular Ca

The parallel fibers (PFs) in the cerebellar cortex extend several millimeters along a folium in the mediolateral direction. The PFs are orthogonal to and cross several parasagittal zones defined by the olivocerebellar and corticonuclear pathways and the expression of molecular markers on Purkinje cells (PCs). The functions of these two organizations remain unclear, including whether the bands respond similarly or differentially to PF input. By using flavoprotein imaging in the anesthetized mouse in vivo, this study demonstrates that high-frequency PF stimulation, which activates a beamlike response at short latency, also evokes patches of activation at long latencies. These patches consist of increased fluorescence along the beam at latencies of 20–25 s with peak activation at 35 s. The long-latency patches are completely blocked by the type 1 metabotropic glutamate receptor (mGluR1) antagonist LY367385. Conversely, the AMPA and NMDA glutamate receptor antagonists DNQX and APV have little effect. Organized in parasagittal bands, the long-latency patches align with zebrin II-positive PC stripes. Additional Ca2+ imaging demonstrates that the patches reflect increases in intracellular Ca2+. Both the PLCβ inhibitor U73122 and the ryanodine receptor inhibitor ryanodine completely block the long-latency patches, indicating that the patches are due to Ca2+ release from intracellular stores. Robust, mGluR1-dependent long-term potentiation (LTP) of the patches is induced using a high-frequency PF stimulation conditioning paradigm that generates LTP of PF-PC synapses. Therefore, the parasagittal bands, as defined by the molecular compartmentalization of PCs, respond differentially to PF inputs via mGluR1-mediated release of internal Ca2+.

scholarly journals Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

2021 ◽  
Vol 15 ◽  
Author(s):  
Bing-Xue Li ◽  
Guang-Hui Dong ◽  
Hao-Long Li ◽  
Jia-Song Zhang ◽  
Yan-Hua Bing ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Sensory Information ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Chronic Ethanol Exposure ◽  
Adult Mice

Sensory information is transferred to the cerebellar cortex via the mossy fiber–granule cell (MF–GC) pathway, which participates in motor coordination and motor learning. We previously reported that chronic ethanol exposure from adolescence facilitated the sensory-evoked molecular layer interneuron–Purkinje cell synaptic transmission in adult mice in vivo. Herein, we investigated the effect of chronic ethanol exposure from adolescence on facial stimulation-evoked MF–GC synaptic transmission in the adult mouse cerebellar cortex using electrophysiological recording techniques and pharmacological methods. Chronic ethanol exposure from adolescence induced an enhancement of facial stimulation-evoked MF–GC synaptic transmission in the cerebellar cortex of adult mice. The application of an N-methyl-D-aspartate receptor (NMDAR) antagonist, D-APV (250 μM), induced stronger depression of facial stimulation-evoked MF–GC synaptic transmission in chronic ethanol-exposed mice compared with that in control mice. Chronic ethanol exposure-induced facilitation of facial stimulation evoked by MF–GC synaptic transmission was abolished by a selective GluN2A antagonist, PEAQX (10 μM), but was unaffected by the application of a selective GluN2B antagonist, TCN-237 (10 μM), or a type 1 metabotropic glutamate receptor blocker, JNJ16259685 (10 μM). These results indicate that chronic ethanol exposure from adolescence enhances facial stimulation-evoked MF–GC synaptic transmission via GluN2A, which suggests that chronic ethanol exposure from adolescence impairs the high-fidelity transmission capability of sensory information in the cerebellar cortex by enhancing the NMDAR-mediated components of MF–GC synaptic transmission in adult mice in vivo.

scholarly journals Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice

2019 ◽  
Vol 51 (8) ◽  
pp. 379-389 ◽  
Author(s):  
Yu-Han Hung ◽  
Matt Kanke ◽  
C. Lisa Kurtz ◽  
Rebecca Cubitt ◽  
Rodica P. Bunaciu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Energy Homeostasis ◽  
Fasting Blood Glucose ◽  
Locked Nucleic Acid ◽  
Small Rna Sequencing ◽  
Sequencing Analysis ◽  
Adult Mice

MicroRNAs (miRNAs) are important posttranscriptional regulators of metabolism and energy homeostasis. Dysregulation of certain miRNAs in the liver has been shown to contribute to the pathogenesis of Type 2 diabetes (T2D), in part by impairing hepatic insulin sensitivity. By small RNA-sequencing analysis, we identified seven hepatic miRNAs (including miR-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin resistance (IR). We also showed that hepatic miR-29b exhibits persistent dysregulation during disease progression in a rat model of diabetes, UCD-T2DM. Furthermore, we observed that hepatic levels of miR-29 family members are attenuated by interventions known to improve IR in rodent and rhesus macaque models. To examine the function of the miR-29 family in modulating insulin sensitivity, we used locked nucleic acid (LNA) technology and demonstrated that acute in vivo suppression of the miR-29 family in adult mice leads to significant reduction of fasting blood glucose (in both chow-fed lean and high-fat diet-fed obese mice) and improvement in insulin sensitivity (in chow-fed lean mice). We carried out whole transcriptome studies and uncovered candidate mechanisms, including regulation of DNA methyltransferase 3a ( Dnmt3a) and the hormone-encoding gene Energy homeostasis associated ( Enho). In sum, we showed that IR/T2D is linked to dysregulation of hepatic miR-29b across numerous models and that acute suppression of the miR-29 family in adult mice leads to improved glycemic control. Future studies should investigate the therapeutic utility of miR-29 suppression in different metabolic disease states. Enho; insulin resistance; liver; microRNA-29 (miR-29); UCD-T2DM

scholarly journals Somatic calcium level reports integrated spiking activity of cerebellar interneurons in vitro and in vivo

2011 ◽  
Vol 106 (4) ◽  
pp. 1793-1805 ◽  
Author(s):  
Romain Franconville ◽  
Gaëlle Revet ◽  
Guadalupe Astorga ◽  
Beat Schwaller ◽  
Isabel Llano
Keyword(s):  
Time Course ◽  
Molecular Layer ◽  
Concentration Data ◽  
Two Photon Microscopy ◽  
Adult Mice ◽  
Intracellular Ca ◽  
The Relationship ◽  
Spiking Activity

We examined the relationship between somatic Ca2+ signals and spiking activity of cerebellar molecular layer interneurons (MLIs) in adult mice. Using two-photon microscopy in conjunction with cell-attached recordings in slices, we show that in tonically firing MLIs loaded with high-affinity Ca2+ probes, Ca2+-dependent fluorescence transients are absent. Spike-triggered averages of fluorescence traces for MLIs spiking at low rates revealed that the fluorescence change associated with an action potential is small (1% of the basal fluorescence). To uncover the relationship between intracellular Ca2+ concentration ([Ca2+]i) and firing rates, spikes were transiently silenced with puffs of the GABAA receptor agonist muscimol. [Ca2+]i relaxed toward basal levels following a single exponential whose amplitude correlated to the preceding spike frequency. The relaxation time constant was slow (2.5 s) and independent of the probe concentration. Data from parvalbumin (PV)−/− animals indicate that PV controls the amplitude and decay time of spike-triggered averages as well as the time course of [Ca2+]i relaxations following spike silencing. The [Ca2+]i signals were sensitive to the L-type Ca2+ channel blocker nimodipine and insensitive to ryanodine. In anesthetized mice, as in slices, fluorescence traces from most MLIs did not show spontaneous transients. They nonetheless responded to muscimol iontophoresis with relaxations similar to those obtained in vitro, suggesting a state of tonic firing with estimated spiking rates ranging from 2 to 30 Hz. Altogether, the [Ca2+]i signal appears to reflect the integral of the spiking activity in MLIs. We propose that the muscimol silencing strategy can be extended to other tonically spiking neurons with similar [Ca2+]i homeostasis.

scholarly journals Quantitative Measurements of Cerebral Blood Oxygen Saturation Using Magnetic Resonance Imaging

2000 ◽  
Vol 20 (8) ◽  
pp. 1225-1236 ◽  
Author(s):  
Hongyu An ◽  
Weili Lin
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Oxygen Saturation ◽  
Spin Echo ◽  
Oxygen Metabolism ◽  
Whole Body ◽  
Blood Oxygen ◽  
Resonance Imaging ◽  
Blood Oxygen Saturation

A quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease because of the fact that it could potentially provide information on tissue viability in vivo. In the current study, a multi-echo gradient and spin echo magnetic resonance imaging sequence was used to acquire images from eight normal volunteer subjects. All images were acquired on a Siemens 1.5T Symphony whole-body scanner (Siemens, Erlangen, Germany). A theoretical signal model, which describes the signal dephasing phenomena in the presence of deoxyhemoglobin, was used for postprocessing of the acquired images and obtaining a quantitative measurement of cerebral blood oxygen saturation in vivo. With a region-of-interest analysis, a mean cerebral blood oxygen saturation of 58.4% ± 1.8% was obtained in the brain parenchyma from all volunteers. It is in excellent agreement with the known cerebral blood oxygen saturation under normal physiologic conditions in humans. Although further studies are needed to overcome some of the confounding factors affecting the estimates of cerebral blood oxygen saturation, these preliminary results are encouraging and should open a new avenue for the noninvasive investigation of cerebral oxygen metabolism under different pathophysiologic conditions using a magnetic resonance imaging approach.

scholarly journals Mode Switch of Ca2 + Oscillation-Mediated Uterine Peristalsis and Associated Embryo Implantation Impairments in Mouse Adenomyosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingzi Qu ◽  
Ping Lu ◽  
Karl Bellve ◽  
Lawrence M. Lifshitz ◽  
Ronghua ZhuGe
Keyword(s):  
Tissue Injury ◽  
Embryo Implantation ◽  
Peak Frequency ◽  
Mode Switch ◽  
Adult Mice ◽  
Receptor Modulator ◽  
Intracellular Ca ◽  
Injury And Repair ◽  
Uterine Peristalsis

Adenomyosis is a debilitating gynecological disease of the uterus with no medicinal cure. The tissue injury and repair hypothesis for adenomyosis suggests that uterine hyperperistalsis or dysperistalsis plays a pivotal role in establishing adenomyotic lesions. However, specific impairments in uterine peristalsis and the underlying cellular signals for these changes in adenomyosis remain elusive. Here, we report a precision-cut uterine slice preparation that preserves in vivo uterine architecture and generates peristalsis similar to that seen in the whole uterus. We found that uterine peristalsis in neonatal mice at day 14 and adult mice at day 55 presents as bursts with multiple peaks induced by intracellular Ca2+ oscillations. Using a mouse model of adenomyosis induced by tamoxifen, a selective estrogen receptor modulator, we discovered that uterine peristalsis and Ca2+ oscillations from adenomyotic uteri on days 14 and 55 become spikes (single peaks) with smaller amplitudes. The peak frequency of Ca2+ oscillations or peristalsis does not show a difference between control and adenomyotic mice. However, both the estimated force generated by uterine peristalsis and the total Ca2+ raised by Ca2+ oscillations are smaller in uteri from adenomyotic mice. Uteri from adenomyotic mice on day 14, but not on day 55, exhibit hyperresponsiveness to oxytocin. Embryo implantations are decreased in adenomyotic adult mice. Our results reveal a mode switch from bursts to spikes (rather than an increased peak frequency) of uterine Ca2+ oscillations and peristalsis and concurrent hyperresponsiveness to oxytocin in the neonatal stage are two characteristics of adenomyosis. These characteristics may contribute to embryo implantation impairments and decreased fertility in adenomyosis.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

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