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Journal of Nanobiotechnology Jun 2024Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability,...
Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.
PubMed: 38918787
DOI: 10.1186/s12951-024-02595-1 -
The Journal of Neuroscience : the... Jun 2024Metabotropic glutamate receptor 8 (mGlu8) is a heterogeneously expressed and poorly understood glutamate receptor with potential pharmacological significance. The...
Metabotropic glutamate receptor 8 (mGlu8) is a heterogeneously expressed and poorly understood glutamate receptor with potential pharmacological significance. The thalamic reticular nucleus (TRN) is a critical inhibitory modulator of the thalamocortical-corticothalamic (TC-CT) network and plays a crucial role in information processing throughout the brain, is implicated in a variety of psychiatric conditions, and is also a site of significant mGlu8 expression. Using both male and female mice, we determined via fluorescent hybridization that parvalbumin-expressing cells in the TRN core and shell matrices (identified by and expression, respectively) as well as the cortical layers involved in corticothalamic signaling, express mRNA. We then assayed the physiological and behavioral impacts of perturbing signaling in the TC circuit through conditional (AAV-CRE mediated) and cell type-specific constitutive deletion strategies. We show that constitutive parvalbumin knockout (PV KO) mice exhibited 1) increased spontaneous excitatory drive onto dorsal thalamus relay cells and 2) impaired sensorimotor gating, measured via paired-pulse inhibition, but observed no differences in locomotion and thigmotaxis in repeated bouts of open field testing. Conversely, we observed hyperlocomotive phenotypes and anxiolytic effects of AAV-mediated conditional knockdown of in the TRN (TRN KD) in repeated open field testing. Our findings underscore a role for mGlu8 in regulating excitatory neurotransmission as well as anxiety-related locomotor behavior and sensorimotor gating, revealing potential therapeutic applications for various neuropsychiatric disorders and guiding future research endeavors into mGlu8 signaling and TRN function. Group III mGlu receptors and the Thalamic Reticular Nucleus (TRN) are critical modulators of reciprocal cortico-thalamic neurotransmission and are implicated in anxiety and locomotor behaviors. The present study demonstrates a specific enrichment of mRNA within the TRN and thalamus-projecting cortical layers and characterizes the role of mGlu8 receptors in controlling spontaneous excitatory neurotransmission onto cells located within the dorsal thalamus and regulating sensorimotor behaviors from open field and PPI testing. These findings add to growing bodies of literature regarding both TRN and regulation of thalamocortical activity and related behaviors implicated in neurological and neuropsychiatric disorders.
PubMed: 38918065
DOI: 10.1523/JNEUROSCI.0119-24.2024 -
ENeuro Jun 2024The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae....
The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae. In this study, we examined the involvement of the anterior tuberal nucleus (AT) in auditory processing in adult zebrafish. Our tract-tracing experiments revealed that the dorsal subdivision of AT is strongly bidirectionally connected to the central nucleus of the torus semicircularis (TSc), a major auditory nucleus in fishes. Immunohistochemical visualisation of the ribosomal protein S6 (pS6) phosphorylation to map neural activity in response to auditory stimulation substantiated this finding: the dorsal but not the ventral part of AT responded strongly to auditory stimulation. A similar response to auditory stimulation was present in the TSc but not in the nucleus isthmi (NI), a visual region, which we used as a control for testing if the pS6 activation was specific to the auditory stimulation. We also measured the time course of pS6 phosphorylation, which was previously unreported in teleost fish. After auditory stimulation, we found that pS6 phosphorylation peaked between 100-130 minutes and returned to baseline levels after 190 minutes. This information will be valuable for the design of future pS6 experiments. Our results suggest an anatomical and functional subdivision of AT, where only the dorsal part connects to the auditory network and processes auditory information. We investigated the involvement of the anterior tuberal nucleus in zebrafish in auditory processing. Our study revealed a functional and anatomical subdivision of this region. We show that its dorsal subdivision is strongly connected to the central nucleus of the torus semicircularis, a major auditory nucleus in fishes. pS6 phosphorylation, as an indirect marker of neuronal activity after auditory stimulation, substantiated that only the dorsal anterior tuberal nucleus, processes auditory information. We also show that after auditory stimulation, pS6 phosphorylation peaked between 100-130 minutes and returned to baseline levels after 190 minutes, providing valuable information for future studies.
PubMed: 38918052
DOI: 10.1523/ENEURO.0062-24.2024 -
Journal of Reconstructive Microsurgery Jun 2024When free tissue transfer is precluded or undesired, the pedicled trapezius flap is a viable alternative for adults requiring complex head and neck (H&N) defect...
BACKGROUND
When free tissue transfer is precluded or undesired, the pedicled trapezius flap is a viable alternative for adults requiring complex head and neck (H&N) defect reconstruction. However, the application of this flap in pediatric reconstruction is underexplored. This systematic review aimed to describe the use of the pedicled trapezius flap and investigate its efficacy in pediatric H&N reconstruction.
METHODS
A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles describing the trapezius flap for H&N reconstruction in pediatric patients were included. Patient demographics, surgical indications, wound characteristics, flap characteristics, complications, and functional outcomes were abstracted.
RESULTS
A systematic review identified 22 articles for inclusion. Studies mainly consisted of case reports ( = 11) and case series ( = 8). In total, 67 pedicled trapezius flaps were successfully performed for H&N reconstruction in 63 patients. The most common surgical indications included burn scar contractures ( = 46, 73.0%) and chronic wounds secondary to H&N masses ( = 9, 14.3%). Defects were most commonly located in the neck ( = 28, 41.8%). The mean flap area and arc of rotation were 326.4 ± 241.7 cm and 157.6 ± 33.2 degrees, respectively. Most flaps were myocutaneous ( = 48, 71.6%) and based on the dorsal scapular artery ( = 32, 47.8%). Complications occurred in 10 (14.9%) flaps. The flap's survival rate was 100% ( = 67). No instances of functional donor site morbidity were reported. The mean follow-up was 2.2 ± 1.8 years.
CONCLUSION
This systematic review demonstrated the reliability of the pedicled trapezius flap in pediatric H&N reconstruction, with a low complication rate, no reports of functional donor site morbidity, and a 100% flap survival rate. The flap's substantial surface area, bulk, and arc of rotation contribute to its efficacy in covering soft tissue defects ranging from the proximal neck to the vertex of the scalp. The pedicled trapezius flap is a viable option for pediatric H&N reconstruction.
PubMed: 38917840
DOI: 10.1055/s-0044-1787741 -
Advances in Experimental Medicine and... 2024In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a... (Review)
Review
In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.
Topics: Basal Ganglia; Animals; Humans; Time Perception; Neurons; Sensation
PubMed: 38918350
DOI: 10.1007/978-3-031-60183-5_8 -
Experimental Brain Research Jun 2024The purpose of the present study was to elucidate whether an external reference frame contributes to tactile localization in blindfolded healthy humans. In a session,...
The purpose of the present study was to elucidate whether an external reference frame contributes to tactile localization in blindfolded healthy humans. In a session, the right forearm was passively moved until the elbow finally reached to the target angle, and participants reached the left index finger to the right middle fingertip. The locus of the right middle fingertip indicated by the participants deviated in the direction of the elbow extension when vibration was provided to the biceps brachii muscle during the passive movement. This finding indicates that proprioception contributes to the identification of the spatial coordinate of the specific body part in an external reference frame. In another session, the tactile stimulus was provided to the dorsal of the right hand during the passive movement, and the participants reached the left index finger to the spatial locus at which the tactile stimulus was provided. Vibration to the biceps brachii muscle did not change the perceived locus of the tactile stimulus indicated by the left index finger. This finding indicates that an external reference frame does not contribute to tactile localization during the passive movement. Humans may estimate the spatial coordinate of the tactile stimulus based on the time between the movement onset and the time at which the tactile stimulus is provided.
PubMed: 38918211
DOI: 10.1007/s00221-024-06877-w -
PLoS Biology Jun 2024Low and high beta frequency rhythms were observed in the motor cortex, but their respective sources and behavioral correlates remain unknown. We studied local field...
Low and high beta frequency rhythms were observed in the motor cortex, but their respective sources and behavioral correlates remain unknown. We studied local field potentials (LFPs) during pre-cued reaching behavior in macaques. They contained a low beta band (<20 Hz) dominant in primary motor cortex and a high beta band (>20 Hz) dominant in dorsal premotor cortex (PMd). Low beta correlated positively with reaction time (RT) from visual cue onset and negatively with uninstructed hand postural micro-movements throughout the trial. High beta reflected temporal task prediction, with selective modulations before and during cues, which were enhanced in moments of increased focal attention when the gaze was on the work area. This double-dissociation in sources and behavioral correlates of motor cortical low and high beta, with respect to both task-instructed and spontaneous behavior, reconciles the largely disparate roles proposed for the beta rhythm, by suggesting band-specific roles in both movement control and spatiotemporal attention.
Topics: Animals; Motor Cortex; Attention; Beta Rhythm; Movement; Reaction Time; Macaca mulatta; Male; Cues; Psychomotor Performance
PubMed: 38917200
DOI: 10.1371/journal.pbio.3002670 -
Proceedings of the National Academy of... Jul 2024Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition...
Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition occurs and whether its restoration alleviates allodynic pain are poorly understood. Here, we show that a critical step in the loss of inhibitory tone is the change in the firing pattern of inhibitory parvalbumin (PV)-expressing neurons (PVNs). Our results show that PV, a calcium-binding protein, controls the firing activity of PVNs by enabling them to sustain high-frequency tonic firing patterns. Upon nerve injury, PVNs transition to adaptive firing and decrease their PV expression. Interestingly, decreased PV is necessary and sufficient for the development of mechanical allodynia and the transition of PVNs to adaptive firing. This transition of the firing pattern is due to the recruitment of calcium-activated potassium (SK) channels, and blocking them during chronic pain restores normal tonic firing and alleviates chronic pain. Our findings indicate that PV is essential for controlling the firing pattern of PVNs and for preventing allodynia. Developing approaches to manipulate these mechanisms may lead to different strategies for chronic pain relief.
Topics: Parvalbumins; Animals; Chronic Pain; Mice; Neurons; Hyperalgesia; Male; Action Potentials; Small-Conductance Calcium-Activated Potassium Channels
PubMed: 38916998
DOI: 10.1073/pnas.2403777121 -
Acta Veterinaria Hungarica Jun 2024The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical...
The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG).The study was performed on 13 mixed breed dogs affected by retinal atrophy (11 males and 2 females that were 1.5-14 years old). Depending on the advancement of RA, SD-OCT examinations identified retinal abnormalities ranging from layer disorganisation to advanced atrophy. The most advanced RA occurred ventral to the optic disc. Total retinal thickness in both eyes (mean ± SD) was lower in dogs with RA compared to controls dorsally (77.7 ± 39.5 μm vs 173.5 ± 13.3 μm), ventrally (33.4 ± 29.9 μm vs 139.5 ± 10.8 μm), nasally (65.0 ± 34.5 μm vs 163.9 ± 11.0 μm) and temporally (61.8 ± 41.7 μm vs 171.9 ± 11.1 μm) to the optic disc. In dogs with locally normal architecture of inner retina, loss of definition of outer retinal layers occurred in many regions. Dark and light-adapted ERGs were reduced in 2 dogs with RA and were unrecordable in 11 dogs. Lesions evident in SD-OCT scans of mixed breed dogs affected with retinal atrophy initially appear ventrally to the optic disc and ventro-dorsally in advanced RA. In all mixed breed dogs with retinal atrophy, clinical signs and SD-OCT results correlate with ERG findings.
PubMed: 38916958
DOI: 10.1556/004.2024.00872 -
Brain Structure & Function Jun 2024In layer II of the entorhinal cortex, the principal neurons that project to the dentate gyrus and the CA3/2 hippocampal fields markedly express the large glycoprotein...
In layer II of the entorhinal cortex, the principal neurons that project to the dentate gyrus and the CA3/2 hippocampal fields markedly express the large glycoprotein reelin (Re + ECLII neurons). In rodents, neurons located at the dorsal extreme of the EC, which border the rhinal fissure, express the highest levels, and the expression gradually decreases at levels successively further away from the rhinal fissure. Here, we test two predictions deducible from the hypothesis that reelin expression is strongly correlated with neuronal metabolic rate. Since the mitochondrial turnover rate serves as a proxy for energy expenditure, the mitophagy rate arguably also qualifies as such. Because messenger RNA of the canonical promitophagic BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) is known to be highly expressed in the EC, we predicted that Bnip3 would be upregulated in Re + ECLII neurons, and that the degree of upregulation would strongly correlate with the expression level of reelin in these neurons. We confirm both predictions, supporting that the energy requirement of Re + ECLII neurons is generally high and that there is a systematic increase in metabolic rate as one moves successively closer to the rhinal fissure. Intriguingly, the systematic variation in energy requirement of the neurons that manifest the observed reelin gradient appears to be consonant with the level of spatial and temporal detail by which they encode information about the external environment.
PubMed: 38916724
DOI: 10.1007/s00429-024-02816-1