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Neuroscience Bulletin May 2024The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas....
The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
PubMed: 38801564
DOI: 10.1007/s12264-024-01229-8 -
Biotechnology Journal May 2024Small extracellular vesicles (sEVs) are nanosized vesicles enclosed in a lipid membrane released by nearly all cell types. sEVs have been considered as reliable...
Small extracellular vesicles (sEVs) are nanosized vesicles enclosed in a lipid membrane released by nearly all cell types. sEVs have been considered as reliable biomarkers for diagnostics and effective carriers. Despite the clear importance of sEV functionality, sEV research faces challenges imposed by the small size and precise imaging of sEVs. Recent advances in live and high-resolution microscopy, combined with efficient labeling strategies, enable us to investigate the composition and behavior of EVs within living organisms. Here, a modified sEVs was generated with a near infrared fluorescence protein mKate2 using a VSVG viral pseudotyping-based approach for monitoring sEVs. An observed was made that the mKate2-tagged protein can be incorporated into the membranes of sEVs without altering their physical properties. In vivo imaging demonstrates that sEVs labeled with mKate2 exhibit excellent brightness and high photostability, allowing the acquisition of long-term investigation comparable to those achieved with mCherry labeling. Importantly, the mKate2-tagged sEVs show a low toxicity and exhibit a favorable safety profile. Furthermore, the co-expression of mKate2 and rabies virus glycoprotein (RVG) peptide on sEVs enables brain-targeted visualization, suggesting the mKate2 tag does not alter the biodistribution of sEVs. Together, the study presents the mKate2 tag as an efficient tracker for sEVs to monitor tissue-targeting and biodistribution in vivo.
Topics: Extracellular Vesicles; Animals; Mice; Humans; Luminescent Proteins; Brain; Tissue Distribution
PubMed: 38797724
DOI: 10.1002/biot.202400128 -
BMC Veterinary Research May 2024Tick-borne encephalitis (TBE) is a severe human neuroinfection caused by TBE virus (TBEV). TBEV is transmitted by tick bites and by the consumption of unpasteurized...
BACKGROUND
Tick-borne encephalitis (TBE) is a severe human neuroinfection caused by TBE virus (TBEV). TBEV is transmitted by tick bites and by the consumption of unpasteurized dairy products from infected asymptomatic ruminants. In France, several food-borne transmission events have been reported since 2020, raising the question of the level of exposure of domestic ungulates to TBEV. In this study, our objectives were (i) to estimate TBEV seroprevalence and quantify antibodies titres in cattle in the historical endemic area of TBEV in France using the micro virus neutralisation test (MNT) and (ii) to compare the performance of two veterinary cELISA kits with MNT for detecting anti-TBEV antibodies in cattle in various epidemiological contexts. A total of 344 cattle sera from four grid cells of 100 km² in Alsace-Lorraine (endemic region) and 84 from western France, assumed to be TBEV-free, were investigated.
RESULTS
In Alsace-Lorraine, cattle were exposed to the virus with an overall estimated seroprevalence of 57.6% (95% CI: 52.1-62.8%, n = 344), varying locally from 29.9% (95% CI: 21.0-40.0%) to 92.1% (95% CI: 84.5-96.8%). Seroprevalence did not increase with age, with one- to three-year-old cattle being as highly exposed as older ones, suggesting a short-life duration of antibodies. The proportion of sera with MNT titres lower than 1:40 per grid cell decreased with increased seroprevalence. Both cELISA kits showed high specificity (> 90%) and low sensitivity (less than 78.1%) compared with MNT. Sensitivity was lower for sera with neutralising antibodies titres below 1:40, suggesting that sensitivity of these tests varied with local virus circulation intensity.
CONCLUSIONS
Our results highlight that cattle were highly exposed to TBEV. Screening strategy and serological tests should be carefully chosen according to the purpose of the serological study and with regard to the limitations of each method.
Topics: Animals; Cattle; Encephalitis, Tick-Borne; Encephalitis Viruses, Tick-Borne; France; Seroepidemiologic Studies; Cattle Diseases; Antibodies, Viral; Female; Male; Neutralization Tests; Endemic Diseases
PubMed: 38796429
DOI: 10.1186/s12917-024-04079-8 -
Viruses Apr 2024Rabies is a fatal encephalitic infectious disease caused by the rabies virus (RABV). RABV is highly neurotropic and replicates in neuronal cell lines . The RABV fixed...
Rabies is a fatal encephalitic infectious disease caused by the rabies virus (RABV). RABV is highly neurotropic and replicates in neuronal cell lines . The RABV fixed strain, HEP-Flury, was produced via passaging in primary chicken embryonic fibroblast cells. HEP-Flury showed rapid adaptation when propagated in mouse neuroblastoma (MNA) cells. In this study, we compared the growth of our previously constructed recombinant HEP (rHEP) strain-based on the sequence of the HEP (HEP-Flury) strain-with that of the original HEP strain. The original HEP strain exhibited higher titer than rHEP and a single substitution at position 80 in the matrix (M) protein M(D80N) after incubation in MNA cells, which was absent in rHEP. , intracerebral inoculation of the rHEP-M(D80N) strain with this substitution resulted in enhanced viral growth in the mouse brain and a significant loss of body weight in the adult mice. The number of viral antigen-positive cells in the brains of adult mice inoculated with the rHEP-M(D80N) strain was significantly higher than that with the rHEP strain at 5 days post-inoculation. Our findings demonstrate that a single amino acid substitution in the M protein M(D80N) is associated with neurovirulence in mice owing to adaptation to mouse neuronal cells.
Topics: Animals; Rabies virus; Mice; Amino Acid Substitution; Virulence; Brain; Viral Matrix Proteins; Rabies; Neurons; Virus Replication; Cell Line
PubMed: 38793581
DOI: 10.3390/v16050699 -
Bioengineering (Basel, Switzerland) May 2024Cell therapy has proven to be a promising treatment for a range of neurological disorders, including Parkinson Disease, drug-resistant epilepsy, and stroke, by restoring... (Review)
Review
Cell therapy has proven to be a promising treatment for a range of neurological disorders, including Parkinson Disease, drug-resistant epilepsy, and stroke, by restoring function after brain damage. Nevertheless, evaluating the true effectiveness of these therapeutic interventions requires a deep understanding of the functional integration of grafted cells into existing neural networks. This review explores a powerful arsenal of molecular techniques revolutionizing our ability to unveil functional integration of grafted cells within the host brain. From precise manipulation of neuronal activity to pinpoint the functional contribution of transplanted cells by using opto- and chemo-genetics, to real-time monitoring of neuronal dynamics shedding light on functional connectivity within the reconstructed circuits by using genetically encoded (calcium) indicators . Finally, structural reconstruction and mapping communication pathways between grafted and host neurons can be achieved by monosynaptic tracing with viral vectors. The cutting-edge toolbox presented here holds immense promise for elucidating the impact of cell therapy on neural circuitry and guiding the development of more effective treatments for neurological disorders.
PubMed: 38790353
DOI: 10.3390/bioengineering11050487 -
International Immunopharmacology Jun 2024Vaccines are used for the control of infectious diseases of animals. Over other types of vaccinations like live attenuated or killed vaccines, mRNA-based vaccines have... (Review)
Review
Vaccines are used for the control of infectious diseases of animals. Over other types of vaccinations like live attenuated or killed vaccines, mRNA-based vaccines have significant advantages. As only a small portion of the pathogen's genetic material is employed and the dose rate of mRNA-based vaccines is low, there is the least possibility that the pathogen will reverse itself. A carrier or vehicle that shields mRNA-based vaccines from the host's cellular RNases is necessary for their delivery. mRNA vaccines have been shown to be effective and to induce both a cell-mediated immune response and a humoral immune response in clinical trials against various infectious diseases (viral and parasitic) affecting the animals, including rabies, foot and mouth disease, toxoplasmosis, Zikavirus, leishmaniasis, and COVID-19. The current review aims to highlight the use of mRNA-based vaccines both in viral and parasitic diseases of animals.
Topics: Animals; Humans; mRNA Vaccines; COVID-19; Communicable Diseases; Vaccines, Synthetic; Viral Vaccines; RNA, Messenger; Virus Diseases; SARS-CoV-2
PubMed: 38788451
DOI: 10.1016/j.intimp.2024.112320 -
Journal of Nanobiotechnology May 2024Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and...
Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer's disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ, we developed an Aβ and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ misfolding, accelerating Aβ clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
Topics: Alzheimer Disease; Animals; Reactive Oxygen Species; Amyloid beta-Peptides; Nanocomposites; Mice; Cerium; Mice, Transgenic; Silicon Dioxide; Peptide Fragments; Humans; Brain; Nanoparticles; Glycoproteins; Disease Models, Animal; Viral Proteins
PubMed: 38783363
DOI: 10.1186/s12951-024-02543-z -
Vector Borne and Zoonotic Diseases... May 2024The burden of zoonotic diseases in developing countries is significantly underestimated, influenced by various factors such as misdiagnosis, underreporting, natural... (Review)
Review
The burden of zoonotic diseases in developing countries is significantly underestimated, influenced by various factors such as misdiagnosis, underreporting, natural disasters, climate change, resource limitations, rapid unplanned urbanization, poverty, animal migration, travel, ecotourism, and the tropical environmental conditions prevalent in the region. Despite Sri Lanka's provision of a publicly funded free health care system, zoonoses still contribute significantly to the burden of communicable diseases in the country. This study serves as a timely and exhaustive systematic review of zoonoses reported over the past 22 years in Sri Lanka. This systematic review adhered to the guidelines provided by the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statement. A systematic literature search was conducted between July and September 2022, utilizing the following databases and sources: Google Scholar, PubMed, Cochrane Library, Weekly Epidemiological Reports, and Rabies Statistical Bulletins published by the Ministry of Health, Sri Lanka. From the initial database search, 1,710 articles were identified. After excluding nonzoonotic diseases, duplicated reports, inaccessible articles, and those not meeting the inclusion criteria, 570 reports were evaluated for eligibility. Of these, 91 reports were selected for data extraction, comprising 58 original research articles, 10 case reports, 16 weekly epidemiological reports, and 7 rabies statistical bulletins. Over the study period (2000-2022), 14 parasitic, 7 bacterial, and 7 viral zoonoses have been reported in Sri Lanka. Notably, leptospirosis emerged as the most reported zoonotic disease in the country. In response to these findings, we strongly recommend the implementation of a tailored, country-specific prevention and control program. To achieve this goal effectively, we emphasize the importance of adopting a country-specific "One Health" approach as a comprehensive framework for managing and controlling zoonotic diseases in Sri Lanka.
PubMed: 38775108
DOI: 10.1089/vbz.2023.0141 -
BioRxiv : the Preprint Server For... May 2024The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons which regulate responses to a variety of interoceptive and...
The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons which regulate responses to a variety of interoceptive and cutaneous sensory signals. The lateral PB subpopulation expressing the gene which produces the neuropeptide calcitonin gene-related peptide (CGRP) relays signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet the afferents to these neurons are only partially understood. We mapped the afferent projections to the lateral part of the PB in mice using conventional cholera toxin B subunit (CTb) retrograde tracing, and then used conditional rabies virus retrograde tracing to map monosynaptic inputs specifically targeting the PB neurons. Using vesicular GABA (vGAT) and glutamate (vGLUT2) transporter reporter mice, we found that lateral PB neurons receive GABAergic afferents from regions such as the lateral part of the central nucleus of the amygdala, lateral dorsal subnucleus of the bed nucleus of the stria terminalis, substantia innominata, and the ventrolateral periaqueductal gray. Additionally, they receive glutamatergic afferents from the infralimbic and insular cortex, paraventricular nucleus, parasubthalamic nucleus, trigeminal complex, medullary reticular nucleus, and nucleus of the solitary tract. Using anterograde tracing and confocal microscopy, we then identified close axonal appositions between these afferents and PB neurons. Finally, we used channelrhodopsin-assisted circuit mapping to test whether some of these inputs directly synapse upon the PB neurons. These findings provide a comprehensive neuroanatomical framework for understanding the afferent projections regulating the PB neurons.
PubMed: 38766214
DOI: 10.1101/2024.05.07.593004 -
Clinical and Experimental Vaccine... Apr 2024Alopecia areata (AA) is an autoimmune-related disorder characterized by non-scarring hair loss in children. We report the case of a child who had AA after the fifth dose...
Alopecia areata (AA) is an autoimmune-related disorder characterized by non-scarring hair loss in children. We report the case of a child who had AA after the fifth dose of rabies vaccine and summarized various potential mechanisms of vaccination induced AA. This case indicates that rabies vaccine might be a predisposition of AA by causing immune dysregulation.
PubMed: 38752007
DOI: 10.7774/cevr.2024.13.2.171