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ENeuro Mar 2024Layer 4 of the rodent somatosensory cortex has unitary structures called barrels that receive tactile information from individual vibrissae. Barrels in the anterolateral...
Layer 4 of the rodent somatosensory cortex has unitary structures called barrels that receive tactile information from individual vibrissae. Barrels in the anterolateral barrel subfield (ALBSF) are much smaller and have gained less attention than larger barrels in the posteromedial barrel subfield (PMBSF), though the former outnumber the latter. We compared the morphological features of barrels between the ALBSF and PMBSF in male mice using deformation-free tangential sections and confocal optical slice-based, precise reconstructions of barrels. The average volume of a single barrel in the ALBSF was 34.7% of that in the PMBSF, but the numerical density of parvalbumin (PV)-positive interneurons in the former was 1.49 times higher than that in the latter. Moreover, PV neuron density in septa was 2.08 times higher in the ALBSF than that in the PMBSF. The proportions of PV neuron number to both all neuron number and all GABAergic neuron number in the ALBSF were also higher than those in the PMBSF. Somata of PV neurons in barrels and septa in the ALBSF received 1.64 and 1.50 times more vesicular glutamate transporter Type 2-labeled boutons than those in the PMBSF, suggesting more potent feedforward inhibitory circuits in the ALBSF. The mode of connectivity through dendritic gap junctions among PV neurons also differed between the ALBSF and PMBSF. Clusters of smaller unitary structures containing a higher density of representative GABAergic interneurons with differential morphological features in the ALBSF suggest a division of functional roles in the two vibrissa-barrel systems, as has been demonstrated by behavioral studies.
Topics: Mice; Animals; Male; Parvalbumins; Interneurons; Somatosensory Cortex; Vibrissae; GABAergic Neurons; Cell Count
PubMed: 38438262
DOI: 10.1523/ENEURO.0518-22.2024 -
Carbohydrate Polymers May 2024Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase...
Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly(l-lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.
Topics: Animals; Chitosan; Hydrogels; Chitin; Liquid Crystals; Vibrissae; Tissue Scaffolds; Bone Regeneration; Tissue Engineering; Osteogenesis; Extracellular Matrix; Anti-Bacterial Agents
PubMed: 38431420
DOI: 10.1016/j.carbpol.2024.121927 -
Veterinary Research Communications Jun 2024This preliminary study suggests a way to artificially extend vibrissae of blind dogs to assist ambulation and avoiding facial contact with obstacles.
OBJECTIVE
This preliminary study suggests a way to artificially extend vibrissae of blind dogs to assist ambulation and avoiding facial contact with obstacles.
PROCEDURES
Fourteen irreversibly blind dogs had 5-6 mystacial vibrissae on each side of the face supplementally extended by attaching carefully chosen adult pig hairs to them and were subjected to a maze test before and after the procedure. In three of these dogs the test was repeated one more time after all the extensions had fallen off. Collision counts and course times with and without extensions were analyzed and compared. A p-value > 0.05 was considered significant.
RESULTS
Median number of collisions was significantly higher post-extensions (5 IQR 2.25) and after extensions had fallen off (4 IQR 7.50) compared to pre-extensions (1 IQR 1), p = 0.021. Median times were significantly higher pre-extension (25.6 IQR 8.98) and after the extensions had fallen off, compared to the post-extension performance (22.8 IQR 8.55), p = 0.04.
CONCLUSION
Vibrissae play an important role in the tactile perception of blind dogs, and our preliminary results suggest that extending this sensory organ possibly improves obstacle location and their quality of life.
Topics: Animals; Dogs; Blindness; Vibrissae; Touch; Male; Female; Dog Diseases
PubMed: 38427268
DOI: 10.1007/s11259-024-10342-y -
Journal of Neuroinflammation Feb 2024The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are...
BACKGROUND
The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure.
METHODS
A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION's CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain.
RESULTS
CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION's CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION's CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION.
CONCLUSION
IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.
Topics: Rats; Animals; Interleukin-6; Rats, Sprague-Dawley; STAT3 Transcription Factor; Gliosis; Constriction; Hyperalgesia; Neuralgia; Cytokines
PubMed: 38419042
DOI: 10.1186/s12974-024-03049-z -
Frontiers in Veterinary Science 2024Free-ranging white-tailed deer () in northeastern lower Michigan, (United States) are a self-sustaining reservoir for bovine tuberculosis (bTB). Farm mitigation...
INTRODUCTION
Free-ranging white-tailed deer () in northeastern lower Michigan, (United States) are a self-sustaining reservoir for bovine tuberculosis (bTB). Farm mitigation practices, baiting bans, and antlerless deer harvests have been ineffective in eliminating bTB in white-tailed deer and risks to cattle. The apparent prevalence has remained relatively constant in deer, prompting interest among wildlife researchers, managers, and veterinarians for an effective means of vaccinating deer against bTB. The commonly used human vaccine for bTB, Bacillus Calmette Guerin (BCG), is the primary candidate with oral delivery being the logical means for vaccinating deer.
MATERIALS AND METHODS
We developed vaccine delivery units and incorporated the biomarker Rhodamine B before delivering them to deer to assess the level of coverage achievable. Following deployment of Rhodamine B-laden vaccine delivery units on 17 agricultural study sites in Alpena County, MI in Mar/Apr 2016, we sampled deer to detect evidence of Rhodamine B consumption.
RESULTS AND DISCUSSION
We collected a total of 116 deer and sampled them for vibrissae/rumen marking and found 66.3% ( = 77) of the deer collected exhibited evidence of vaccine delivery unit consumption. Understanding the level of coverage we achieved with oral delivery of a biomarker in vaccine delivery units to deer enables natural resource professionals to forecast expectations of a next step toward further minimizing bTB in deer.
PubMed: 38414651
DOI: 10.3389/fvets.2024.1354772 -
Toxins Feb 2024Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and...
Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.
Topics: Animals; Mice; Bee Venoms; Cell Proliferation; Hair; Intercellular Signaling Peptides and Proteins; Stem Cells; Cells, Cultured
PubMed: 38393162
DOI: 10.3390/toxins16020084 -
Nature Communications Feb 2024Astrocytes express ionotropic receptors, including N-methyl-D-aspartate receptors (NMDARs). However, the contribution of NMDARs to astrocyte-neuron interactions,...
Astrocytes express ionotropic receptors, including N-methyl-D-aspartate receptors (NMDARs). However, the contribution of NMDARs to astrocyte-neuron interactions, particularly in vivo, has not been elucidated. Here we show that a knockdown approach to selectively reduce NMDARs in mouse cortical astrocytes decreases astrocyte Ca transients evoked by sensory stimulation. Astrocyte NMDAR knockdown also impairs nearby neuronal circuits by elevating spontaneous neuron activity and limiting neuronal recruitment, synchronization, and adaptation during sensory stimulation. Furthermore, this compromises the optimal processing of sensory information since the sensory acuity of the mice is reduced during a whisker-dependent tactile discrimination task. Lastly, we rescue the effects of astrocyte NMDAR knockdown on neurons and improve the tactile acuity of the animal by supplying exogenous ATP. Overall, our findings show that astrocytes can respond to nearby neuronal activity via their NMDAR, and that these receptors are an important component for purinergic signaling that regulate astrocyte-neuron interactions and cortical sensory discrimination in vivo.
Topics: Mice; Animals; Astrocytes; Receptors, N-Methyl-D-Aspartate; Vibrissae; Neurons; Signal Transduction
PubMed: 38383567
DOI: 10.1038/s41467-024-45989-3 -
Scientific Reports Feb 2024Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge....
Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation. Our results suggest that, depending on the type of gephyrin PTM, the neuronal activities of L2/3 pyramidal neurons can be differentially modulated, leading to changes in the size of the neuronal population responding to the single-whisker stimulation. Furthermore, we show that gephyrin PTMs have their preference for selecting synaptic GABA receptor subunits. Our results identify an important role of gephyrin and GABAergic postsynaptic sites for cortical microcircuit function during sensory stimulation.
Topics: Animals; Receptors, GABA-A; Vibrissae; Carrier Proteins; Pyramidal Cells; Synapses; Membrane Proteins
PubMed: 38379020
DOI: 10.1038/s41598-024-54720-7 -
Bioinspiration & Biomimetics Mar 2024The spanwise undulated cylinder geometry inspired by seal whiskers has been shown to alter shedding frequency and reduce fluid forces significantly compared to smooth...
The spanwise undulated cylinder geometry inspired by seal whiskers has been shown to alter shedding frequency and reduce fluid forces significantly compared to smooth cylindrical geometry. Prior research has parameterized the whisker-inspired geometry and demonstrated the relevance of geometric variations on force reduction properties. Among the geometric parameters, undulation wavelength was identified as a significant contributor to forcing changes. To analyze the effect of undulation wavelength, a thorough investigation isolating changes in wavelength is performed to expand upon previous research that parameterized whisker-inspired geometry and the relevance of geometric variations on the force reduction properties. A set of five whisker-inspired models of varying wavelength are computationally simulated at a Reynolds number of 250 and compared with an equivalent aspect ratio smooth elliptical cylinder. Above a critical non-dimensional value, the undulation wavelength reduces the amplitude and frequency of vortex shedding accompanied by a reduction in oscillating lift force. Frequency shedding is tied to the creation of wavelength-dependent vortex structures which vary across the whisker span. These vortices produce distinct shedding modes in which the frequency and phase of downstream structures interact to decrease the oscillating lift forces on the whisker model with particular effectiveness around the wavelength values typically found in nature. The culmination of these location-based modes produces a complex and spanwise-dependent lift frequency spectra at those wavelengths exhibiting maximum force reduction. Understanding the mechanisms of unsteady force reduction and the relationship between undulation wavelength and frequency spectra is critical for the application of this geometry to vibration tuning and passive flow control for vortex-induced vibration (VIV) reduction.
Topics: Animals; Vibrissae; Seals, Earless; Vibration
PubMed: 38377615
DOI: 10.1088/1748-3190/ad2b04 -
International Journal of Nanomedicine 2024Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone...
Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.
BACKGROUND
Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.
METHODS
CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.
RESULTS
This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.
CONCLUSION
Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.
Topics: Animals; Rats; Cell Proliferation; Exosomes; Facial Nerve; Hypoxia; Mesenchymal Stem Cells; MicroRNAs; Nerve Regeneration; RNA, Circular; Schwann Cells; Mediator Complex; Carrier Proteins
PubMed: 38371458
DOI: 10.2147/IJN.S443036