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1.
Int J Mol Sci ; 25(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39000372

RESUMO

Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2. Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2, Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.


Assuntos
Adipócitos , Fibrose , Gerbillinae , Intolerância à Glucose , Animais , Feminino , Adipócitos/metabolismo , Adipócitos/patologia , Masculino , Intolerância à Glucose/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Ritmo Circadiano
2.
PLoS Negl Trop Dis ; 18(7): e0012302, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950061

RESUMO

BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.


Assuntos
Cerebelo , Gerbillinae , Giardia lamblia , Giardíase , Hipocampo , Zinco , Animais , Gerbillinae/parasitologia , Zinco/deficiência , Zinco/metabolismo , Giardíase/parasitologia , Giardíase/patologia , Cerebelo/patologia , Cerebelo/parasitologia , Hipocampo/patologia , Hipocampo/parasitologia , Giardia lamblia/crescimento & desenvolvimento , Masculino , Modelos Animais de Doenças
3.
Hippocampus ; 34(8): 422-437, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838068

RESUMO

Remembering what just happened is a crucial prerequisite to form long-term memories but also for establishing and maintaining working memory. So far there is no general agreement about cortical mechanisms that support short-term memory. Using a classifier-based decoding approach, we report that hippocampal activity during few sparsely distributed brief time intervals contains information about the previous sensory motor experience of rodents. These intervals are characterized by only a small increase of firing rate of only a few neurons. These low-rate predictive patterns are present in both working memory and non-working memory tasks, in two rodent species, rats and Mongolian gerbils, are strongly reduced for rats with medial entorhinal cortex lesions, and depend on the familiarity of the sensory-motor context.


Assuntos
Potenciais de Ação , Gerbillinae , Hipocampo , Memória de Curto Prazo , Animais , Hipocampo/fisiologia , Masculino , Ratos , Memória de Curto Prazo/fisiologia , Potenciais de Ação/fisiologia , Neurônios/fisiologia , Córtex Entorrinal/fisiologia , Reconhecimento Psicológico/fisiologia , Comportamento Animal/fisiologia
4.
Proc Natl Acad Sci U S A ; 121(24): e2311570121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38830095

RESUMO

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.


Assuntos
Córtex Auditivo , Gerbillinae , Perda Auditiva , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/fisiopatologia , Perda Auditiva/genética , Perda Auditiva/fisiopatologia , Receptores de GABA-B/metabolismo , Receptores de GABA-B/genética , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética , Parvalbuminas/metabolismo , Parvalbuminas/genética , Percepção Auditiva/fisiologia , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Vetores Genéticos/genética
5.
Genes (Basel) ; 15(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38927752

RESUMO

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time.


Assuntos
Gerbillinae , Polimorfismo de Nucleotídeo Único , Animais , Gerbillinae/genética , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Genoma/métodos , Técnicas de Genotipagem/métodos , Genética Populacional/métodos , China , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos
6.
EBioMedicine ; 105: 105188, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38848649

RESUMO

BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis (GPELF) is the largest public health program based on mass drug administration (MDA). Despite decades of MDA, ongoing transmission in some countries remains a challenge. To optimise interventions, it is critical to differentiate between recrudescence and new infections. Since adult filariae are inaccessible in humans, deriving a method that relies on the offspring microfilariae (mf) is necessary. METHODS: We developed a genome amplification and kinship analysis-based approach using Brugia malayi samples from gerbils, and applied it to analyse Wuchereria bancrofti mf from humans in Côte d'Ivoire. We examined the pre-treatment genetic diversity in 269 mf collected from 18 participants, and further analysed 1-year post-treatment samples of 74 mf from 4 participants. Hemizygosity of the male X-chromosome allowed for direct inference of haplotypes, facilitating robust maternal parentage inference. To enrich parasite DNA from samples contaminated with host DNA, a whole-exome capture panel was created for W. bancrofti. FINDINGS: By reconstructing and temporally tracking sibling relationships across pre- and post-treatment samples, we differentiated between new and established maternal families, suggesting reinfection in one participant and recrudescence in three participants. The estimated number of reproductively active adult females ranged between 3 and 11 in the studied participants. Population structure analysis revealed genetically distinct parasites in Côte d'Ivoire compared to samples from other countries. Exome capture identified protein-coding variants with ∼95% genotype concordance rate. INTERPRETATION: We have generated resources to facilitate the development of molecular genetic tools that can estimate adult worm burdens and monitor parasite populations, thus providing essential information for the successful implementation of GPELF. FUNDING: This work was financially supported by the Bill and Melinda Gates Foundation (https://www.gatesfoundation.org) under grant OPP1201530 (Co-PIs PUF & Gary J. Weil). B. malayi parasite material was generated with support of the Foundation for Barnes Jewish Hospital (PUF). In addition, the development of computational methods was supported by the National Institutes of Health under grants AI144161 (MM) and AI146353 (MM). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Assuntos
Filariose Linfática , Recidiva , Reinfecção , Wuchereria bancrofti , Filariose Linfática/parasitologia , Filariose Linfática/epidemiologia , Filariose Linfática/diagnóstico , Filariose Linfática/genética , Humanos , Animais , Wuchereria bancrofti/genética , Feminino , Masculino , Reinfecção/parasitologia , Brugia Malayi/genética , Gerbillinae/parasitologia , Variação Genética , Microfilárias/genética , Adulto , Haplótipos , Côte d'Ivoire/epidemiologia
7.
Metab Brain Dis ; 39(5): 705-718, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795262

RESUMO

Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.


Assuntos
Aconitum , Gerbillinae , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , AVC Isquêmico/metabolismo , AVC Isquêmico/prevenção & controle
8.
Tissue Cell ; 88: 102396, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703582

RESUMO

By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts.


Assuntos
Caderinas , Diabetes Mellitus Tipo 2 , Modelos Animais de Doenças , Gerbillinae , Fígado , Fator de Necrose Tumoral alfa , Animais , Fator de Necrose Tumoral alfa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Caderinas/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Doenças Metabólicas/patologia , Doenças Metabólicas/metabolismo , Masculino
9.
Commun Biol ; 7(1): 600, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762693

RESUMO

Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations. Our knowledge regarding OoC mechanics has advanced over the past decade thanks to the application of tomographic vibrometry. However, recent data from live cochlea experiments often led to diverging interpretations due to complicated interaction between passive and active responses, lack of image resolution in vibrometry, and ambiguous measurement angles. We present motion measurements and analyses of the OoC sub-components at the close-to-true cross-section, measured from acutely excised gerbil cochleae. Specifically, we focused on the vibrating patterns of the reticular lamina, the outer pillar cell, and the basilar membrane because they form a structural frame encasing active outer hair cells. For passive transmission, the OoC frame serves as a rigid truss. In contrast, motile outer hair cells exploit their frame structures to deflect the upper compartment of the OoC while minimally disturbing its bottom side (basilar membrane). Such asymmetric OoC vibrations due to outer hair cell motility explain how recent observations deviate from the classical cochlear amplification theory.


Assuntos
Gerbillinae , Células Ciliadas Auditivas Externas , Órgão Espiral , Vibração , Animais , Gerbillinae/fisiologia , Células Ciliadas Auditivas Externas/fisiologia , Órgão Espiral/fisiologia , Órgão Espiral/citologia , Cóclea/fisiologia , Cóclea/citologia , Membrana Basilar/fisiologia
10.
Diabetes Res Clin Pract ; 212: 111656, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636847

RESUMO

Mitochondrial dysfunction is a significant feature of type 2 diabetes. MOTS-C, a peptide derived from mitochondria, has positive effects on metabolism and exercise capacity. This study explored the impact of high and moderate-intensity interval exercises on mitochondrial MOTS-C alterations and their correlation with metabolic markers in male diabetic sand rats. Thirty male sand rats were divided into six groups: control, MIIT, DM + HIIT, DM + MIIT, DM, and HIIT (5 rats each). Diabetes was induced using a high-fat diet (HFD) combined with streptozotocin (STZ). The Wistar sand rats in exercise groups underwent 8 weeks of interval training of varying intensities. Post sample collection, protein expressions of PCG-1a, AMPK, and GLUT4 were assessed through Western blot analysis, while MOTS-C protein expression was determined using ELISA. Both exercise intensity and diabetes significantly affected the levels of PCG-1a, MOTS-C, GLUT4 proteins, and insulin resistance (p < 0.001). The combined effect of diabetes status and exercise intensity on these levels was also significant (p < 0.001). However, the diabetes effect varied when comparing high-intensity to moderate-intensity exercise. The moderate-intensity exercise group with diabetes showed higher levels of PCG-1a, MOTS-C, and GLUT4 proteins and reduced insulin resistance levels (p < 0.001). Exercise intensity (p = 0.022) and diabetes (p = 0.008) significantly influenced AMPK protein levels. The interplay between diabetes status and exercise intensity on AMPK protein levels was noteworthy, with the moderate-intensity diabetes group exhibiting higher AMPK levels than the high-intensity diabetes group (p < 0.001). In conclusion, exercise elevates the levels of PCG-1a, MOTS-C, GLUT4, and AMPK proteins, regulating insulin resistance in diabetic sand rats. Given the AMPK-MOTS-C mitochondrial pathway's mechanisms, interval exercises might enhance the metabolic rates and general health of diabetic rodents.


Assuntos
Diabetes Mellitus Experimental , Condicionamento Físico Animal , Animais , Masculino , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Diabetes Mellitus Experimental/metabolismo , Ratos , Transportador de Glucose Tipo 4/metabolismo , Treinamento Intervalado de Alta Intensidade/métodos , Gerbillinae , Mitocôndrias/metabolismo , Biomarcadores/metabolismo , Resistência à Insulina/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Ratos Wistar
11.
Adv Healthc Mater ; 13(16): e2304513, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608269

RESUMO

With the growth of optogenetic research, the demand for optical probes tailored to specific applications is ever rising. Specifically, for applications like the coiled cochlea of the inner ear, where planar, stiff, and nonconformable probes can hardly be used, transitioning from commonly used stiff glass fibers to flexible probes is required, especially for long-term use. Following this demand, polydimethylsiloxane (PDMS) with its lower Young's modulus compared to glass fibers can serve as material of choice. Hence, the long-term usability of PDMS as a waveguide material with respect to variations in transmission and refractive index over time is investigated. Different manufacturing methods for PDMS-based flexible waveguides are established and compared with the aim to minimize optical losses and thus maximize optical output power. Finally, the waveguides with lowest optical losses (-4.8 dB cm-1 ± 1.3 dB cm-1 at 472 nm) are successfully inserted into the optogenetically modified cochlea of a Mongolian gerbil (Meriones unguiculatus), where optical stimuli delivered by the waveguides evoked robust neuronal responses in the auditory pathway.


Assuntos
Dimetilpolisiloxanos , Gerbillinae , Optogenética , Dimetilpolisiloxanos/química , Animais , Optogenética/métodos , Cóclea/fisiologia
12.
PLoS Biol ; 22(4): e3002586, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38683852

RESUMO

Having two ears enables us to localize sound sources by exploiting interaural time differences (ITDs) in sound arrival. Principal neurons of the medial superior olive (MSO) are sensitive to ITD, and each MSO neuron responds optimally to a best ITD (bITD). In many cells, especially those tuned to low sound frequencies, these bITDs correspond to ITDs for which the contralateral ear leads, and are often larger than the ecologically relevant range, defined by the ratio of the interaural distance and the speed of sound. Using in vivo recordings in gerbils, we found that shortly after hearing onset the bITDs were even more contralaterally leading than found in adult gerbils, and travel latencies for contralateral sound-evoked activity clearly exceeded those for ipsilateral sounds. During the following weeks, both these latencies and their interaural difference decreased. A computational model indicated that spike timing-dependent plasticity can underlie this fine-tuning. Our results suggest that MSO neurons start out with a strong predisposition toward contralateral sounds due to their longer neural travel latencies, but that, especially in high-frequency neurons, this predisposition is subsequently mitigated by differential developmental fine-tuning of the travel latencies.


Assuntos
Estimulação Acústica , Gerbillinae , Neurônios , Complexo Olivar Superior , Animais , Neurônios/fisiologia , Complexo Olivar Superior/fisiologia , Localização de Som/fisiologia , Masculino , Núcleo Olivar/fisiologia , Som , Feminino
13.
Folia Histochem Cytobiol ; 62(1): 37-49, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38563048

RESUMO

INTRODUCTION: Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal Mongolian gerbil is a member of the rodent family Muridae that exhibits unique physiological, anatomical, and behavioral differences from the nocturnal rat and mouse, which render it a useful model for studying the visual system. The purpose of this study was to confirm the distribution and morphology of neurons that contain nitric oxide synthase (NOS) and their pattern of co-expressing NOS with neuropeptide Y (NPY), somatostatin (SST), and gamma-aminobutyric acid (GABA) in the visual cortex of Mongolian gerbils. MATERIALS AND METHODS: Mongolian gerbils were used in the study. We confirmed the localization of NOS in the visual cortex of Mongolian gerbils using horseradish peroxidase immunocytochemistry, fluorescent immunocytochemistry, and conventional confocal microscopy. RESULTS: NOS-immunoreactive (IR) neurons were present in all layers of the visual cortex of the Mongolian gerbil, with the exception of layer I, with the highest density observed in layer V (50.00%). The predominant type of NOS-IR neurons was multipolar round/oval cells (60.96%). Two-color immunofluorescence revealed that 100% NOS-IR neurons were co-labeled with NPY and SST and 34.55% were co-labeled with GABA. CONCLUSIONS: Our findings of the laminar distribution and morphological characteristics of NOS-IR neurons, as well as the colocalization patterns of NOS-IR neurons with NPY, SST, and GABA, indicated the presence of species-specific differences, suggesting the functional diversity of NO in the visual cortex. This study provides valuable data on the anatomical organization of NOS-IR neurons and, consequently, a better understanding of the functional aspects of NO and species diversity.


Assuntos
Neurônios , Córtex Visual , Ratos , Camundongos , Animais , Gerbillinae/metabolismo , Neurônios/metabolismo , Óxido Nítrico Sintase/metabolismo , Ácido gama-Aminobutírico/metabolismo
14.
Parasitol Res ; 123(4): 186, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634933

RESUMO

Onchocerciasis is a devastating skin and eye disease that afflicts about 21 million people, most of whom live in sub-Saharan Africa. Its control with the microfilaricidal drug ivermectin is limited, thus necessitating the development of preclinical animal models to aid in the discovery of a macrofilaricide. Previously, we found that Onchocerca ochengi (the closest relative of the human O. volvulus) worm masses survive better in hamsters than in gerbils. The aim of this study was to compare the survival of O. ochengi adult male worms and their susceptibility to flubendazole (FBZ, a macrofilaricide) in gerbils and hamsters. The animals were intraperitoneally implanted with O. ochengi male worms, treated with FBZ, and sacrificed 35 days post-implantation. Unlike gerbils which had some worms moving freely in the peritoneum and some in newly formed nodules (neo-nodules), all the worms in the hamsters were found in neo-nodules. FBZ significantly decreased worm burden, motility, and viability in gerbils whereas it had no significant effect in hamsters. These results highlight a major difference in how O. ochengi adult male worms are sustained and affected by FBZ in gerbils compared to hamsters. Understanding the difference between these two models is important in the development of effective macrofilaricides for onchocerciasis.


Assuntos
Mebendazol/análogos & derivados , Onchocerca , Oncocercose , Adulto , Animais , Cricetinae , Humanos , Masculino , Gerbillinae
15.
PLoS One ; 19(4): e0296214, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625985

RESUMO

We aimed to investigate whether two closely related but socially distinct species of gerbils differ in personality patterns. Using a suit of multivariate repeated assays (docility test, dark-light emergence test, startle test, novel object test, elevated platform test, and stranger test), we assessed contextual and temporal consistency of docility, boldness, exploration, anxiety, and sociability in the solitary midday gerbil, Meriones meridianus, and social Mongolian gerbil, M. unguiculatus. We revealed contextually consistent and highly repeatable sex-independent but species-specific personality traits. Species differed in temporal repeatability of different behaviours, and contextual consistency was more pronounced in solitary M. meridianus than in social M. unguiculatus. This finding contradicts the social niche specialization hypothesis, which suggests that personality traits should be more consistent in more social species. Instead, we hypothesize that social complexity should favour more flexible and less consistent behavioural traits. The habituation effect indicative of learning abilities was weak in both species yet stronger in social M. unguiculatus, supporting the relationship between the sociality level and cognitive skills. In both species, only a few different behavioural traits covaried, and the sets of correlated behaviours were species-specific such that the two species did not share any pair of correlated traits. Between-species differences in personality traits, habituation, and behavioural syndromes may be linked to differences in sociality. The lack of prominent behavioural syndromes is consistent with the idea that context-specific individual behavioural traits might be favoured to allow more flexible and adequate responses to changing environments than syndromes of correlated functionally different behaviours.


Assuntos
Comportamento Animal , Personalidade , Animais , Gerbillinae , Comportamento Animal/fisiologia , Personalidade/fisiologia , Comportamento Social , Transtornos da Personalidade
16.
Mar Drugs ; 22(4)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38667787

RESUMO

Porphyran, a sulfated polysaccharide found in various species of marine red algae, has been demonstrated to exhibit diverse bioactivities, including anti-inflammatory effects. However, the protective effects of porphyran against cerebral ischemia and reperfusion (IR) injury have not been investigated. The aim of this study was to examine the neuroprotective effects of porphyran against brain IR injury and its underlying mechanisms using a gerbil model of transient forebrain ischemia (IR in the forebrain), which results in pyramidal cell (principal neuron) loss in the cornu ammonis 1 (CA1) subregion of the hippocampus on day 4 after IR. Porphyran (25 and 50 mg/kg) was orally administered daily for one week prior to IR. Pretreatment with 50 mg/kg of porphyran, but not 25 mg/kg, significantly attenuated locomotor hyperactivity and protected pyramidal cells located in the CA1 area from IR injury. The pretreatment with 50 mg/kg of porphyran significantly suppressed the IR-induced activation and proliferation of microglia in the CA1 subregion. Additionally, the pretreatment significantly inhibited the overexpressions of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing protein-3 (NLRP3) inflammasome complex, and pro-inflammatory cytokines (interleukin 1 beta and interleukin 18) induced by IR in the CA1 subregion. Overall, our findings suggest that porphyran exerts neuroprotective effects against brain IR injury, potentially by reducing the reaction (activation) and proliferation of microglia and reducing NLRP3 inflammasome-mediated neuroinflammation.


Assuntos
Região CA1 Hipocampal , Gerbillinae , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Sefarose/análogos & derivados , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Masculino , Traumatismo por Reperfusão/tratamento farmacológico , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Modelos Animais de Doenças , Microglia/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Polissacarídeos/farmacologia , Neurônios/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo
17.
Sci Data ; 11(1): 411, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649691

RESUMO

This dataset was collected to study the functional consequences of age-related hearing loss for the auditory nerve, which carries acoustic information from the periphery to the central auditory system. Using high-impedance glass electrodes, raw voltage traces and spike times were recorded from more than one thousand single fibres of the auditory nerve of young-adult, middle-aged, and old Mongolian gerbils raised in a quiet environment. The dataset contains not only responses to simple acoustic stimuli to characterize the fibres, but also to more complex stimuli, such as speech logatomes in background noise and Schroeder-phase stimuli. A software toolbox is provided to search through the dataset, to plot various analysed outcomes, and to give insight into the analyses. This dataset may serve as a valuable resource to test further hypotheses about age-related hearing loss. Additionally, it can aid in optimizing available computational models of the auditory system, which can contribute to, or eventually even fully replace, animal experiments.


Assuntos
Envelhecimento , Nervo Coclear , Gerbillinae , Animais , Gerbillinae/fisiologia , Nervo Coclear/fisiologia , Estimulação Acústica
18.
Exp Parasitol ; 261: 108768, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679124

RESUMO

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus.


Assuntos
Anti-Helmínticos , Catalase , Gerbillinae , Glutationa , Hemoncose , Haemonchus , Estresse Oxidativo , Extratos Vegetais , Folhas de Planta , Superóxido Dismutase , Animais , Haemonchus/efeitos dos fármacos , Folhas de Planta/química , Estresse Oxidativo/efeitos dos fármacos , Hemoncose/veterinária , Hemoncose/tratamento farmacológico , Hemoncose/parasitologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Catalase/análise , Glutationa/metabolismo , Glutationa/análise , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Contagem de Ovos de Parasitas/veterinária , Biomarcadores , Glutationa Peroxidase/metabolismo , Feminino
19.
J Pharmacol Sci ; 155(2): 29-34, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677783

RESUMO

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.


Assuntos
Aminopiridinas , Encéfalo , Gerbillinae , Microglia , Pirróis , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos , Animais , Cricetinae , Administração Oral , Aminopiridinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/citologia , Mesocricetus , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais , Pirróis/farmacologia , Pirrolidinas/farmacologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Especificidade da Espécie
20.
Behav Brain Res ; 465: 114928, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38432301

RESUMO

Testosterone (T), estrogen receptor alpha (ERα), and androgen receptor (AR) play a significant role in the regulation of paternal behavior. We determined the effects of deprivation of paternal care on alterations in paternal behavior, T concentrations in plasma, and the presence of ERα and AR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB), as well as the corticosterone (CORT) concentrations in plasma caused by deprivation of paternal care in the Mongolian gerbil (Meriones unguiculatus). Twenty pairs of gerbils were formed; the pups were deprived of paternal care (DPC) in 10 pairs. In another 10 pairs, the pups received paternal care (PC). Ten males raised in DPC condition and 10 males raised in PC conditions were mated with virgin females. When they became fathers, each DPC male and PC male was subjected to tests of paternal behavior on day three postpartum. Blood samples were obtained to quantify T and CORT concentrations, and the brains were removed for ERα and AR immunohistochemistry analyses. DPC males gave less care to their pups than PC males, and they had significantly lower T concentrations and levels of ERα and AR in the mPOA and BNST than PC males. DPC males also had higher CORT concentrations than PC males. These results suggest that in the Mongolian gerbil father's absence causes a decrease in paternal care in the offspring, which is associated with alterations in the neuroendocrine mechanisms that regulate it.


Assuntos
Receptores Androgênicos , Núcleos Septais , Animais , Feminino , Masculino , Humanos , Gerbillinae/fisiologia , Receptores Androgênicos/metabolismo , Núcleos Septais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Comportamento Paterno/fisiologia , Área Pré-Óptica/metabolismo , Pai , Corticosterona
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