Notes

Abstracts through the Seventh Yearly Baylor University or college Infirmary Health care Education Study Online community 2021.
Additionally, we present 16 genes that express solely circRNAs, without linear RNAs co-expression, exclusively in young and aged synaptosomes, suggesting a synaptic gene network that functions along canonical splicing activity.Dendrite-targeting somatostatin-expressing interneurons (SST-INs) powerfully control signal integration and synaptic plasticity in pyramidal dendrites during cortical development. We previously showed that synaptic transmission from SST-INs to pyramidal cells (PCs) (SST-IN → PC) in the mouse visual cortex suddenly declined at around the second postnatal week. However, it is unclear what specific postsynaptic mechanisms underlie this developmental change. Using multiple whole-cell patch-clamp recordings, we found that application of an α5-GABAA receptor-selective inverse agonist, alpha5IA, significantly weakened SST-IN → PC unitary inhibitory postsynaptic currents (uIPSCs) in layer 2/3 of the mouse visual cortex, but had no effect on uIPSCs from SST-INs to other types of interneurons. The extent of alpha5IA-induced reduction of SST-IN → PC synaptic transmission was significantly larger at postnatal days 11-13 (P11-13) than P14-17. Moreover, α5-subunit-containing GABAA receptors (α5-GABAARs)-mediated uIPSCs had slow rise and decay kinetics. Apart from pharmacological test, we observed that SST-IN → PC synapses did indeed contain α5-GABAARs by immunogold labeling for electron microscopy. More importantly, coinciding with the weakening of SST-IN → PC synaptic transmission, the number of α5-GABAAR particles in SST-IN → PC synapses significantly decreased at around the second postnatal week. Together, these data indicate that α5-GABAARs are involved in synaptic transmission from SST-INs to PCs in the neocortex, and are significantly diminished around the second postnatal week.The theory of communication through coherence (CTC) posits the synchronization of brain oscillations as a key mechanism for information sharing and perceptual binding. In a parallel literature, hippocampal theta activity (4-10 Hz) has been shown to modulate the appearance of neocortical fast gamma oscillations (100-150 Hz), a phenomenon known as cross-frequency coupling (CFC). Even though CFC has also been previously associated with information routing, it remains to be determined whether it directly relates to CTC. In particular, for the theta-fast gamma example at hand, a critical question is to know if the phase of the theta cycle influences gamma synchronization across the neocortex. To answer this question, we combined CFC (modulation index) and CTC (phase-locking value) metrics in order to detect the modulation of the cross-regional high-frequency synchronization by the phase of slower oscillations. Upon applying this method, we found that the inter-hemispheric synchronization of neocortical fast gamma during REM sleep depends on the instantaneous phase of the theta rhythm. These results show that CFC is likely to aid long-range information transfer by facilitating the synchronization of faster rhythms, thus consistent with classical CTC views.Understanding how the brain decodes sensory information to give rise to behaviour remains an important problem in systems neuroscience. Across various sensory modalities (e.g. auditory, visual), the time-varying contrast of natural stimuli has been shown to carry behaviourally relevant information. However, it is unclear how such information is actually decoded by the brain to evoke perception and behaviour. Here we investigated how midbrain electrosensory neurons respond to weak contrasts in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We found that these neurons displayed lower detection thresholds than their afferent hindbrain electrosensory neurons. Further analysis revealed that the lower detection thresholds of midbrain neurons were not due to increased sensitivity to the stimulus. Rather, these were due to the fact that midbrain neurons displayed lower variability in their firing activities in the absence of stimulation, which is due to lower firing rates. Our results suggest that midbrain neurons play an active role towards enabling the detection of weak stimulus contrasts, which in turn leads to perception and behavioral responses.
To compare in vivo glutamate-weighted chemical exchange saturation transfer (GluCEST-weighted) signal changes between in a rat model of demyelinated multiple sclerosis and control groups.

Using a pre-clinical 7 T magnetic resonance imaging (MRI) system, CEST imaging was applied to a toxin (lysophosphatidylcholine; LPC) induced rat (MS
) and control (CTRL) groups to compare in vivo glutamate signal changes. The GluCEST-weighted signals were analyzed based on the magnetization transfer ratio asymmetry approach at 3.0 ppm on the region-of-interests (ROIs) in the corpus callosum and hippocampus at each hemispheric region.

GluCEST-weighted signals were significantly changed between the CTRL and MS
groups, while higher glutamate signals were indicated in the MS
than the CTRL group ([MS
/ CTRL]; hippocampus [6.159 ± 0.790 / 4.336 ± 0.446] and corpus callosum [-3.545 ± 0.945 / -6.038 ± 0.620], all p = 0.001).

Our results show increased GluCEST-weighted signals in the LPC-induced demyelination rat brain compared with control. GluCEST-weighted imaging could be a useful tool for defining a biomarker to estimate the glutamate-related metabolism in MS.
Our results show increased GluCEST-weighted signals in the LPC-induced demyelination rat brain compared with control. GluCEST-weighted imaging could be a useful tool for defining a biomarker to estimate the glutamate-related metabolism in MS.Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist. HSP inhibitor We investigated the impact of brain CYP2D metabolism on central tramadol and ODSMT levels, and resulting analgesic response after oral tramadol administration in rats. CYP2D inhibitors propranolol and propafenone were administered intracerebroventricularly prior to oral tramadol administration and analgesia was measured by tail-flick latency. Drug levels of tramadol and its metabolites, ODSMT and N-desmethyltramadol, were assessed in plasma and in brain by microdialysis using LC-ESI-MS/MS. Inhibiting brain CYP2D with propafenone pretreatment increased analgesia after oral tramadol administration (ANOVA p = 0.02), resulting in a 1.5-fold increase in area under the analgesia-time curve (AUC0-60, p less then 0.01). This effect was associated with changes in the brain levels of tramadol and its metabolites consistent with brain CYP2D inhibition. In conclusion, under oral tramadol dosing pretreatment with a central administration of the CYP2D inhibitor propafenone increased analgesia (without altering plasma drug or metabolite levels), indicating that tramadol itself (and activity of CYP2D within the brain) contributed to analgesia.Our recent report demonstrated that hesperetin (Hst) as a citrus flavonoid, significantly reduces the levels of demyelination in optic chiasm of rats. Previous evidence also indicated that nano-hesperetin (nano-Hst) possesses beneficial impacts in experimental models of Alzheimer's disease and autism. In this study, the effects of nano-Hst on latency of visual signals, demyelination levels, glial activation, and expression of Olig2 and MBP were evaluated in lysolecithin (LPC)-induced demyelination model. Focal demyelination was induced by injection of LPC (1%, 2 μL) into the rat optic chiasm. Animals received oral administration of nano-Hst at dose of 20 mg/kg for 14 or 21 days post LPC injection. Visual evoked potential (VEP) recording showed that nano-Hst reduces the latency of visual signals and ameliorates the extent of demyelination areas and glial activation. Expression levels of the Olig2 and MBP were also significantly increased in nano-Hst treated rats. Overall, our data suggest that nano-Hst reduces the latency of visual signals through its protective effects on myelin sheath, amelioration of glial activation, and enhancement of endogenous remyelination.The present study was undertaken to further investigate the spinal anti-allodynic effects of endomorphins (EMs) and their C-terminal hydrazide modified analogs EM-1-NHNH2 and EM-2-NHNH2 in the spared nerve injury (SNI) model of neuropathic pain in mice. Our results demonstrated that intrathecal (i.t.) administration of endomorphin-1 (EM-1), endomorphin-2 (EM-2), EM-1-NHNH2 and EM-2-NHNH2 produced potent anti-allodynic effects ipsilaterally in neuropathic pain model. Judging from the area under the curve (AUC) values, these two analogs exhibited higher antinociception than their parent peptides. Moreover, they also displayed significant antinociceptive effects in the contralateral paw administered intrathecally. Interestingly, EM-1 and its analog EM-1-NHNH2 displayed their antinociception probably by μ2-opioid receptor subtype since the μ1-opioid receptor antagonist naloxonazine didn't significantly block the anti-allodynia of EM-1 and EM-1-NHNH2, which implied a same opioid mechanism. However, the anti-allodynia induced by EM-2, but not EM-2-NHNH2 was significantly reduced by both μ1-opioid antagonist, naloxonazine and κ-antagonist, nor-binaltorphamine (nor-BNI), indicating multiple opioid receptors were involved in the anti-allodynic effects of EM-2. Most importantly, EM-1-NHNH2 decreased the antinociceptive tolerance, and EM-2-NHNH2 displayed non-tolerance-forming antinociception. Therefore, C-terminal amide to hydrazide conversion changed the spinal antinociceptive profiles of EMs in neuropathic pain. The present investigation is of great value in the development of novel opioid therapeutics against neuropathic pain.
Dialysis for end stage renal disease is considered a major public health challenge. link2 Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization.

This case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure.

In total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval 3.99-5.05). The ORs for acute-temporary (N=23,418) and chronic dialysis (N=13,291) were 5.57 (4.83-6.42) and 2.37 (1.90-2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N=12,030) were 3.25 (2.53-4.19) and 4.85 (4.24-5.54) in early CKD patients (N=24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57-5.48).

In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. link3 We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.
In this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.
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