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1.
J Integr Neurosci ; 21(3): 95, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35633176

RESUMO

BACKGROUND: The central nervous system (CNS) is enriched in lipids; despite this, studies exploring the functional roles of lipids in the brain are still limited. Sterol regulatory element binding protein (SREBP) signaling is a transcriptomic pathway that predominantly participates in the maintenance of lipid homeostasis; however, its involvement in the CNS dysfunction is not well-established. In this study, we aimed to characterize and pinpoint specific genes of the SREBP pathway which may be implicated in neurodegenerative, neurological, and neuropsychiatric diseases. METHODS: In silico bioinformatic analysis was performed using the open-source databases DisGeNET and MSigDB. Protein-protein interaction data were visualized and analyzed using STRING, after which GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted via DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: Several common genes were identified between the SREBP pathway and CNS disorders. In GO enrichment analysis, the most enriched biological processes included lipid, cholesterol, and steroid biosynthetic processes; the most enriched molecular functions were transcription factor-related; and the most enriched subcellular compartments revealed that the genes involved in CNS disorders were mainly associated with the enzyme complexes of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). In KEGG enrichment analysis, the most enriched pathway was the AMP-activated protein kinase (AMPK) signaling pathway, and the top-ranked genes significantly enriched under this pathway were ACACA, ACACB, FASN, HMGCR, MTOR, PPARGC1A, PRKAA1, SCD, SIRT1, and SREBF1. CONCLUSIONS: The findings of this study strengthen the evidence linking the involvement of lipid homeostasis in CNS functions. We suggest herein the roles of downstream ACC and FASN enzymes and upstream AMPK signaling in the SREBP pathway as mechanisms underlying neurodegenerative, neurological, and neuropsychiatric CNS disorders.


Assuntos
Doenças do Sistema Nervoso Central , Proteínas de Ligação a Elemento Regulador de Esterol , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Lipídeos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas de Ligação a Elemento Regulador de Esterol/genética
2.
Int J Mol Sci ; 23(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35886987

RESUMO

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.


Assuntos
Celulose , Colágeno , Nervo Facial , Células-Tronco Mesenquimais , Nanofibras , Regeneração Nervosa , Animais , Celulose/farmacologia , Materiais Revestidos Biocompatíveis , Colágeno/farmacologia , Modelos Animais de Doenças , Nervo Facial/efeitos dos fármacos , Nervo Facial/fisiologia , Regeneração Tecidual Guiada , Células-Tronco Mesenquimais/fisiologia , Nanofibras/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Ratos , Nervo Isquiático/patologia , Alicerces Teciduais
3.
Int J Mol Sci ; 23(6)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35328770

RESUMO

Neuroplasticity is the capacity of neural networks in the brain to alter through development and rearrangement. It can be classified as structural and functional plasticity. The hippocampus is more susceptible to neuroplasticity as compared to other brain regions. Structural modifications in the hippocampus underpin several neurodegenerative diseases that exhibit cognitive and emotional dysregulation. This article reviews the findings of several preclinical and clinical studies about the role of structural plasticity in the hippocampus in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In this study, literature was surveyed using Google Scholar, PubMed, Web of Science, and Scopus, to review the mechanisms that underlie the alterations in the structural plasticity of the hippocampus in neurodegenerative diseases. This review summarizes the role of structural plasticity in the hippocampus for the etiopathogenesis of neurodegenerative diseases and identifies the current focus and gaps in knowledge about hippocampal dysfunctions. Ultimately, this information will be useful to propel future mechanistic and therapeutic research in neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Hipocampo , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Plasticidade Neuronal/fisiologia
4.
J Integr Neurosci ; 20(2): 307-320, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258929

RESUMO

We evaluated the practicability of using the rarely utilized C57BL/6N mouse as a Parkinson's disease model established via the acute MPTP/probenecid (MPTP/p) protocol. We confirmed dopaminergic degeneration in terms of decreased expression levels of tyrosine hydroxylase in the substantia nigra and striatum of MPTP/p-lesioned mice. In addition, acute MPTP/p-lesioned mice demonstrated initial motor dysfunctions followed by spontaneous recovery. Interestingly, these MPTP/p-lesioned mice exhibited anxiolytic and antidepressive behaviors upon recovery from these motor deficits. Additionally, increased expression of norepinephrine transporters in several brain regions, including the hippocampus, medial prefrontal cortex, and striatum, and an elevated rate of adult neurogenesis (in terms of increased numbers of doublecortin-positive neuroblasts) in the hippocampus were observed after recovery from motor dysfunctions. We suggest that the emotional alterations observed under these experimental conditions may be associated with enhanced adult neurogenesis, increased levels of norepinephrine transporters, and/or a possible interplay between these two factors. Consequently, this acute MPTP/p model adequately satisfies the criteria for the validity of a Parkinson's disease model regarding dopaminergic loss and motor impairment. However, the non-motor findings may offer novel evidence against the practicability of utilizing the acute MPTP/p-lesioned mice for modeling the emotional aberrations found in Parkinson's disease patients.


Assuntos
Comportamento Animal/efeitos dos fármacos , Dopaminérgicos/farmacologia , Neurogênese/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/fisiopatologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL
5.
Int J Mol Sci ; 23(1)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35008469

RESUMO

High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein-an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.


Assuntos
Fármacos Neuroprotetores/farmacologia , Salicilatos/farmacologia , Zumbido/induzido quimicamente , Zumbido/tratamento farmacológico , Ácido Valproico/farmacologia , Animais , Linhagem Celular Tumoral , Ácido Glutâmico/metabolismo , Humanos , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Zumbido/metabolismo
6.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198910

RESUMO

Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.


Assuntos
Espinhas Dendríticas/genética , Memória/fisiologia , Neurônios/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Animais , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiologia , Espinhas Dendríticas/patologia , Regulação da Expressão Gênica/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Camundongos , Camundongos Knockout , Plasticidade Neuronal/genética , Neurônios/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/deficiência
7.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445535

RESUMO

This study aimed to investigate whether the Protaetia brevitarsis seulensis (PB)' water extract (PBWE) ameliorates trimethyltin (TMT)-induced seizures and hippocampal neurodegeneration. To investigate the potential neuroprotective effect of the PBWE in vitro, a lactate dehydrogenase (LDH) assay was conducted in TMT-treated primary cultures of mouse hippocampal neurons. In TMT-treated adult C57BL/6 mice, behavioral and histopathological changes were evaluated by seizure scoring and Fluoro-Jade C staining, respectively. In our in vitro assay, we observed that pretreating mice hippocampal neuron cultures with the PBWE reduced TMT-induced cytotoxicity, as indicated by the decreased LDH release. Furthermore, pretreatment with the PBWE alleviated seizures and hippocampal neurodegeneration in TMT-treated mice. The antioxidant activity of the PBWE increased in a dose-dependent manner; moreover, pretreatment with the PBWE mitigated the TMT-induced Nrf2 stimulation. In addition, six major compounds, including adenine, hypoxanthine, uridine, adenosine, inosine, and benzoic acid, were isolated from the PBWE, and among them, inosine and benzoic acid have been confirmed to have an essential antioxidative activity. In conclusion, the PBWE ameliorated TMT-induced toxicity in hippocampal neurons in both in vitro and in vivo assays, through a potential antioxidative effect. Our findings suggest that the PBWE may have pharmacotherapeutic potential in neurodegenerative diseases such as seizures or epilepsy.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Besouros/química , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Animais , Produtos Biológicos/isolamento & purificação , Biomarcadores , Cromatografia Líquida de Alta Pressão , Besouros/anatomia & histologia , Besouros/classificação , Besouros/genética , Modelos Animais de Doenças , Imunofluorescência , Genes de Insetos , Testes Genéticos , Hipocampo/metabolismo , Hipocampo/patologia , Degeneração Neural/tratamento farmacológico , Degeneração Neural/etiologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo , Fenótipo , Convulsões/tratamento farmacológico , Convulsões/etiologia , Compostos de Trimetilestanho/efeitos adversos
8.
J Neurosci Res ; 98(11): 2333-2348, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32754943

RESUMO

Neuronal plasticity describes changes in structure, function, and connections of neurons. The hippocampus, in particular, has been shown to exhibit considerable plasticity regarding both physiological and morphological functions. Melatonin, a hormone released by the pineal gland, promotes cell survival and dendrite maturation of neurons in the newborn brain and protects against neurological disorders. In this study, we investigated the effect of exogenous melatonin on neuronal architecture and its possible mechanism in the hippocampus of adult male C57BL/6 mice. Melatonin treatment significantly increased the total length and complexity of dendrites in the apical and basal cornu ammonis (CA) 1 and in the dentate gyrus in mouse hippocampi. Spine density in CA1 apical dendrites was increased, but no significant differences in other subregions were observed. In primary cultured hippocampal neurons, the length and arborization of neurites were significantly augmented by melatonin treatment. Additionally, western blot and immunohistochemical analyses in both in vivo and in vitro systems revealed significant increases in the level of cysteine-rich protein 1 (crp-1) protein, which is known to be involved in dendritic branching in mouse hippocampal neurons after melatonin treatment. Our results suggest that exogenous melatonin leads to significant alterations of neuronal micromorphometry in the adult hippocampus, possibly via crp-1 signaling.


Assuntos
Hipocampo/efeitos dos fármacos , Proteínas com Domínio LIM/fisiologia , Melatonina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Proteínas Nucleares/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Dendritos/efeitos dos fármacos , Dendritos/ultraestrutura , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/ultraestrutura , Giro Denteado/efeitos dos fármacos , Giro Denteado/ultraestrutura , Proteínas com Domínio LIM/efeitos dos fármacos , Proteínas com Domínio LIM/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/efeitos dos fármacos , Neuritos/ultraestrutura , Plasticidade Neuronal/efeitos dos fármacos , Proteínas Nucleares/efeitos dos fármacos , Proteínas Nucleares/genética
9.
Int J Mol Sci ; 21(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531902

RESUMO

Lipid homeostasis is an important component of brain function, and its disturbance causes several neurological disorders, such as Huntington's, Alzheimer's, and Parkinson's diseases as well as mood disorders. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key modulatory molecule involved in lipid homeostasis in the central nervous system. However, little is known about the biological effects of SREBP-1c in the brain. Our previous study uncovered that mice deficient in SREBP-1c exhibit schizophrenia-like behaviors. To investigate whether there are novel molecular mechanisms involved in the neurological aberrations caused by SREBP-1c deficiency, we analyzed the transcriptomes of the hippocampus of SREBP-1c knockout (KO) mice and wild-type mice. We found seven differentially expressed genes (three up-regulated and four down-regulated genes) in the hippocampus of SREBP-1c KO mice. For further verification, we selected the three most significantly changed genes: glucagon-like peptide 2 receptors (GLP2R) involved in hippocampal neurogenesis and neuroplasticity as well as in cognitive impairments; necdin (NDN) which is related to neuronal death and neurodevelopmental disorders; and Erb-B2 receptor tyrosine kinase 4 (ERBB4) which is a receptor for schizophrenia-linked protein, neuregulin-1. The protein levels of GLP2R and NDN were considerably decreased, but the level of ERBB4 was significantly increased in the hippocampus of SREBP-1c KO mice. However, further confirmation is warranted to establish the translatability of these findings from this rodent model into human patients. We suggest that these data provide novel molecular evidence for the modulatory role of SREBP-1c in the mouse hippocampus.


Assuntos
Comportamento Animal/fisiologia , Hipocampo/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Animais , Diferenciação Celular/genética , Sobrevivência Celular/genética , Perfilação da Expressão Gênica , Hipocampo/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mapas de Interação de Proteínas/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Esquizofrenia/genética , Transdução de Sinais/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
Elife ; 122023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735291

RESUMO

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Osteogênese , Animais , Masculino , Camundongos , Regeneração Óssea , Diferenciação Celular , Cromatografia Líquida , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Espectrometria de Massas em Tandem
11.
Meat Sci ; 186: 108732, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35026537

RESUMO

The application of natural oil droplets called oleosomes (OSs) as a potential fat replacer in comminuted meat products was investigated by evaluating the influence of rapeseed OS incorporation at 0, 25, 50, 75 and 100% pork fat substitution levels on the technological properties of meat model systems. The moisture content, pH, L* and b* of meat model systems increased while the fat content and a* decreased with the increasing levels of fat replacement. Treatments prepared with OSs showed improvements in emulsion and oxidative stability of meat batters. Texture profile analysis revealed the production of softer, less gummy and less chewy meat systems, whereas micrographs showed smaller-sized fat globules within compact protein matrices as OS levels were increased. Sensory evaluation results exhibited that treatments with partial replacement (≤ 50%) of pork fat by OSs were generally acceptable. The results demonstrate the possibility of maintaining or improving certain technological properties of meat systems with the use of OSs as fat replacer.


Assuntos
Brassica napus , Produtos da Carne , Carne de Porco , Carne Vermelha , Animais , Manipulação de Alimentos , Gotículas Lipídicas , Carne , Produtos da Carne/análise , Óleo de Brassica napus , Suínos
12.
Exp Neurobiol ; 31(6): 419-430, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36631850

RESUMO

There is a scarcity of experimental studies on peripheral nerve regeneration using placental extract (PE). This study aimed to investigate the effects of topical PE application on recovery after crush injury to the rat facial nerve using functional, electrophysiological, and morphological evaluations. The viability of the RSC96 Schwann cells treated with PE (0.5~4 mg/ml) increased significantly. Immunoblot test revealed that PE application enhanced the migration of RSC96 cells. Quantitative polymerase chain reaction demonstrated that PE increased the expression of neurotropic genes. The recovery from vibrissa fibrillation in the PE-treated group was superior to that in the control group. The threshold of action potential was also significantly lower in the PE group. Histopathological examination showed that crushed facial nerves treated with PE exhibited larger axons. The surrounding myelin sheaths were more distinct and thicker in the PE-treated group. Hence, PE may be considered a topical therapeutic agent for treating traumatic facial nerve paralysis.

13.
Int Neurourol J ; 26(Suppl 2): S94-105, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36503212

RESUMO

PURPOSE: Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD. METHODS: Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining. RESULTS: During the 7-8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion. CONCLUSION: The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.

14.
Curr Neuropharmacol ; 19(5): 641-664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32798374

RESUMO

BACKGROUND: Schizophrenia is a serious mental illness that affects more than 21 million people worldwide. Both genetics and the environment play a role in its etiology and pathogenesis. Symptoms of schizophrenia are mainly categorized into positive, negative, and cognitive. One major approach to identify and understand these diverse symptoms in humans has been to study behavioral phenotypes in a range of animal models of schizophrenia. OBJECTIVE: We aimed to provide a comprehensive review of the behavioral tasks commonly used for measuring schizophrenia-like behaviors in rodents together with an update of the recent study findings. METHODS: Articles describing phenotypes of schizophrenia-like behaviors in various animal models were collected through a literature search in Google Scholar, PubMed, Web of Science, and Scopus, with a focus on advances over the last 10 years. RESULTS: Numerous studies have used a range of animal models and behavioral paradigms of schizophrenia to develop antipsychotic drugs for improved therapeutics. In establishing animal models of schizophrenia, the candidate models were evaluated for schizophrenia-like behaviors using several behavioral tasks for positive, negative, and cognitive symptoms designed to verify human symptoms of schizophrenia. Such validated animal models were provided as rapid preclinical avenues for drug testing and mechanistic studies. CONCLUSION: Based on the most recent advances in the field, it is apparent that a myriad of behavior tests are needed to confirm and evaluate the congruency of animal models with the numerous behaviors and clinical signs exhibited by patients with schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Animais , Antipsicóticos/uso terapêutico , Modelos Animais de Doenças , Humanos , Fenótipo , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
15.
Brain Sci ; 11(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201837

RESUMO

Among the animal models of Parkinson's disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.

16.
J Clin Med ; 10(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917576

RESUMO

The success rate of grafting using acellular dermal matrix (ADM) for chronic tympanic membrane was reported in previous studies to be lower than fascia or perichondrium. Combining mesenchymal stem cells (MSCs) and growth factor-loaded ADM for the regeneration of chronic TMP has not been reported so far. In this study, we hypothesized that combining growth factor-loaded ADM/MSCs could promote the recruitment of MSCs and assist in TMP regeneration. We evaluated the regeneration and compared the performance of four scaffolds in both in vitro and in vivo studies. MTT, qPCR, and immunoblotting were performed with MSCs. In vivo study was conducted in 4 groups (control; ADM only, ADM/MSC, ADM/MSC/bFGF, ADM/MSC/EGF) of rats and inferences were made by otoendoscopy and histological changes. Attachment of MSCs on ADM was observed by confocal microscopy. Proliferation rate increased with time in all treated cells. Regeneration-related gene expression in the treated groups was higher. Also, graft success rate was significantly higher in ADM/MSC/EGF group than other groups. Significant relationships were disclosed in neodrum thickness between each group. The results suggest, in future, combining EGF with ADM/MSCs could possibly be used as an outpatient treatment, without the need for surgery for eardrum regeneration.

17.
J Tradit Chin Med ; 41(3): 390-396, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34114396

RESUMO

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing (seq) analysis. METHODS: This study investigated the changes in interaction between messenger ribonucleic acid (mRNA) expression and deoxyribonucleic acid (DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra (SN) region of a MPTP-induced Parkinson's disease (PD) model. RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase (TH) positive neural cells in the SN and striatum of mice. We profiled genome- wide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extract- treated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions. Among them, 47 were negatively correlated down- regulated genes. Nineteen genes out of 47 down- regulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neu- rons including dopamine transporters, TH, dihy- droxyphenylalanine decarboxylase, and dopamine D2 receptor. CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Modelos Animais de Doenças , Epigênese Genética , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Escorpiões
18.
Exp Anim ; 70(2): 185-193, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33239488

RESUMO

Despite decades-long existence of the Philippine stingless bee industry, the biological activity of propolis from this native bee species (Tetragonula biroi Friese) remains poorly understood and sparingly investigated. Herein, we examined the potential anti-inflammatory efficacy of Philippine stingless bee propolis using the lambda (λ)-carrageenan-induced mice model of hind paw edema. Thirty (30), six-week-old, male ICR mice were randomly assigned into three treatment groups (n=10/group) as follows: distilled water group, diclofenac sodium group (10 mg/kg), and propolis group (100 mg/kg). All treatment were administered an hour prior to the injection of the phlogistic agent. As observed at 3 h post-injection, λ-carrageenan remarkably evoked the classical signs of hind paw edema exemplified grossly by swelling and hyperemia. The ameliorative effect of propolis became apparent at the onset of 6 h post-injection with a statistically significant finding evident at the 24-h period. This gross attenuation histologically correlated to a considerable and specific reduction of the dermal edema, which mirrored those of the diclofenac sodium group. Furthermore, both propolis and diclofenac sodium significantly attenuated the λ-carrageenan-induced increase in the protein expression levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) depicting more than two-fold decrement relative to the distilled water group. Altogether, these suggest that Philippine stingless bee propolis also exhibited a promising in vivo anti-inflammatory property, which can be partly mediated through the inhibition of TNF-α.


Assuntos
Apiterapia , Carragenina , Edema , Doenças do Pé , Própole , Substâncias Protetoras , Animais , Masculino , Camundongos , Abelhas/química , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Pé/fisiopatologia , Doenças do Pé/induzido quimicamente , Doenças do Pé/diagnóstico , Camundongos Endogâmicos ICR , Própole/farmacologia , Substâncias Protetoras/farmacologia
19.
Acta Trop ; 211: 105610, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32610092

RESUMO

Rabies is a fatal zoonotic disease endemic in developing countries of Asia and Africa. Recently, the direct rapid immunohistochemical test (DRIT) was recommended by the World Health Organization (WHO) and the World Organization for Animal Health (OIE) as a diagnostic test for rabies. Therefore, a biotinylated polyclonal antibody (pAb) against the rabies lyssavirus (RABV) nucleoprotein was developed using a plasmid cDNA vaccine derived from a challenge virus standard 11 strain. A preliminary evaluation on the efficacy of this reagent in recognizing the Philippine RABV strain was tested using banked canine hippocampal tissue samples with DRIT and the results were compared to dFAT. The effects of acetone and formalin fixation on DRIT were also assessed through immunoreactivity scores of the specimens. Of the 142 samples examined, 104 tested positive and 38 negative using both dFAT and DRIT, showing 100% agreement between the two diagnostic procedures. Moreover, no false positive or false negative results were observed using acetone and formalin fixation. Thus, locally prepared biotinylated pAb from plasmid cDNA can be used for DRIT, especially in resource-limited laboratories in the Philippines. However, these results should be confirmed with a more thorough evaluation of this technique, and the range of detection needs to be further evaluated in a larger panel of animal samples and on other lyssaviruses.


Assuntos
Anticorpos Monoclonais/sangue , Testes Diagnósticos de Rotina/métodos , Imuno-Histoquímica/métodos , Vírus da Raiva/imunologia , Vírus da Raiva/isolamento & purificação , Raiva/diagnóstico , Animais , Feminino , Filipinas/epidemiologia , Coelhos , Raiva/epidemiologia , Raiva/veterinária
20.
J Vet Med Sci ; 81(12): 1863-1867, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31656239

RESUMO

An 18-year-old male Yorkshire Terrier was admitted with a history of neurological signs including dullness and progressive tetraparesis. Physical examination revealed bilaterally symmetrical alopecia and pot-bellied abdomen. Computed tomography and necropsy examination showed a mass across the frontal sinus and cerebral frontal lobe, bilateral adrenocortical hyperplasia, and hepatomegaly. Histopathologically, the tumor lesions consisted of sheets, nests, or cords of small- to medium-sized round-to-polyhedral cells. Adrenal cortex showed bilateral diffuse cellular proliferation, and some hepatocytes showed intracytoplasmic glycogen accumulation. Immunohistochemically, the tumor cells were positive for pancytokeratin, chromogranin-A, neuron-specific enolase, S100, synaptophysin, and thyroid transcription factor-1 but negative for microtubule-associated proein-2 and neurofilament, leading to the diagnosis of neuroendocrine tumor. These tumor cells were also positive for adrenocorticotropic hormone.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Doenças do Cão/patologia , Tumores Neuroendócrinos/veterinária , Hipersecreção Hipofisária de ACTH/veterinária , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/veterinária , Animais , Cães , Hepatomegalia/veterinária , Masculino , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Paresia/veterinária , Tomografia Computadorizada por Raios X
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