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BACKGROUND: Human Adenovirus D-36 (HAdV-D36) promotes adipogenesis in cellular and animal models and may contribute to the development of human obesity. Induction of PPARγ by HAdV-D36 seems to have a central role in the maintenance of adipogenic status. There is limited information about epigenetic mechanisms contributing to this process in human adipose tissue. This study evaluated the expression of lncRNAs (ADINR, GAS5 and MEG3) and miRNAs (miR-18a and miR-140) involved in the adipogenic process in visceral adipose tissue (VAT) of subjects with obesity with previous HAdV-D36 infection (seropositive) and unexposed (seronegative) subjects with obesity. METHODS: Individuals with obesity were grouped according to the presence of antibodies against HAdV-D36 (Seropositive: HAdV-D36[+], n = 29; and Seronegative: HAdV-D36[-], n = 28). Additionally, a group of individuals without obesity (n = 17) was selected as a control group. The HAdV-D36 serology was carried out by ELISA. Biopsies of VAT were obtained during an elective and clinically indicated surgery (bariatric or cholecystectomy). RNA extraction from VAT was performed and the expression of PPARG and non-coding RNAs was evaluated by qPCR. RESULTS: HAdV-D36[+] individuals had lower expression of anti-adipogenic lncRNAs GAS5 (p = 0.016) and MEG3 (p = 0.035) compared with HAdV-D36[-] subjects with obesity. HAdV-D36[+] subjects also presented increased expression of the adipogenic miRNA miR-18a (p = 0.042), which has been reported to be modulated by GAS5 through a RNA sponging mechanism during adipogenic differentiation. Additionally, an inverse correlation of GAS5 with PPARG expression was observed (r = -0.917, p = 0.01). CONCLUSION: Our results suggest that HAdV-D36 is related to non-coding RNAs implicated in adipogenesis, representing a potential mechanism by which previous HAdV-D36 infection could be associated with the long-term maintenance of adipogenic status, probably through the GAS5/miR-18a axis.
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Growing evidence indicates a critical role of astrocytes in learning and memory. However, little is known about the role of basolateral amygdala complex (BLA-C) astrocytes in contextual fear conditioning (CFC), a paradigm relevant to understand and generate treatments for fear- and anxiety-related disorders. To get insights on the involvement of BLA-C astrocytes in fear memory, fluorocitrate (FLC), a reversible astroglial metabolic inhibitor, was applied at critical moments of the memory processing in order to target the acquisition, consolidation, retrieval and reconsolidation process of the fear memory. Adult Wistar male rats were bilaterally cannulated in BLA-C. Ten days later they were infused with different doses of FLC (0.5 or 1 nmol/0.5 µl) or saline before or after CFC and before or after retrieval. FLC impaired fear memory expression when administered before and shortly after CFC, but not one hour later. Infusion of FLC prior and after retrieval did not affect the memory. Our findings suggest that BLA-C astrocytes are critically involved in the acquisition/early consolidation of fear memory but not in the retrieval and reconsolidation. Furthermore, the extinction process was presumably not affected (considering that peri-retrieval administration could also affect this process).
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Astrócitos , Complexo Nuclear Basolateral da Amígdala , Medo , Memória , Ratos Wistar , Animais , Medo/fisiologia , Medo/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/fisiologia , Masculino , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/fisiologia , Ratos , Memória/fisiologia , Memória/efeitos dos fármacos , Citratos/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Consolidação da Memória/fisiologia , Consolidação da Memória/efeitos dos fármacos , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologiaRESUMO
Growth factors, such as insulin-like growth factor 1 (IGF-1), among others are known for their critical involvement in learning and memory processes. IGF-1 regulates cognitive functions, synapse density, neurotransmission, and adult neurogenesis and induces structural and synaptic plasticity-specific changes. Although IGF-1 has been suggested to participate in different memory processes, its role in memories associated with negative emotional experiences still remains to be elucidated. The principal aim of the present study was to test whether IGF-1 overexpression using adenoviral vectors in basolateral amygdala (BLA) influences both the expression and formation of contextual fear memory, as well as the hippocampal structural plasticity associated with such memory trace. We found that IGF-1 overexpression promotes the formation and expression of a specific contextual fear memory trace, and such effect persisted at least 7 days after recall. Moreover, the overexpression of this growth factor in BLA upregulates the activation of the ERK/MAPK pathway in this brain structure. In addition, intra-BLA IGF-1 overexpression causes dorsal hippocampus (DH) structural plasticity modifications promoting changes in the proportion of mature dendritic spines in the CA1 region, after a weak conditioning protocol. The present findings contribute to the knowledge underlying BLA-DH trace memory of fear and reveal important new insights into the neurobiology and neurochemistry of fear acquisition modulated by IGF-1 overexpression. The understanding of how IGF-1 modulates the formation of a fear contextual trace may pave the way for the development of novel therapeutic strategies focused on fear, anxiety, and trauma-related disorders.
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Complexo Nuclear Basolateral da Amígdala , Complexo Nuclear Basolateral da Amígdala/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Memória/fisiologiaRESUMO
Reconsolidation of a contextual fear memory is a protein synthesis-dependent process in which a previously destabilized memory returns to a stable state. This process has become the subject of many studies due to its importance in memory processing, maintenance and updating, and its potential role as a therapeutical target in fear memory disorders such as phobias and post-traumatic stress disorder. In this sense, understanding the underlying mechanisms of memory reconsolidation is paramount in developing potential treatments for such memory dysfunctions. In the present work, we studied the interaction between two key neural structures involved in the reconsolidation process: the basolateral amygdala complex of the amygdala (BLA) and the dorsal hippocampus (DH). Our results show changes in the structural plasticity of the CA1 region of the DH in the form of dendritic spines density changes associated with the destabilization/reconsolidation process. Furthermore, we demonstrate a modulatory role of BLA over such structural plasticity by infusing different drugs such as ifenprodil, a destabilization blocker, and propranolol, a reconsolidation disruptor, in this brain structure. Altogether our work shows a particular temporal dynamic in the CA1 region of DH that accompanies the destabilization/reconsolidation process and aims to provide new information on the underlying mechanisms of this process that potentially contributes for a better understanding of memory storage, maintenance, expression and updating, and its potential medical applications.
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Complexo Nuclear Basolateral da Amígdala , Consolidação da Memória , Tonsila do Cerebelo/metabolismo , Medo , Hipocampo , MemóriaRESUMO
The destabilization/reconsolidation process can be triggered by memory recall, allowing consolidated memories to be modified. We have previously reported that stress prior to fear conditioning induces memories that exhibit resistance to the engagement of some molecular events associated with the destabilization/reconsolidation process. Here, we evaluated whether stress could affect the expression of Lys-48 polyubiquitinated proteins within the basolateral amygdala complex, a phenomenon crucially linked to memory destabilization. As expected, a post-recall increase of Lys-48 polyubiquitinated proteins in control animals was observed; however, this phenomenon was prevented by stress exposure before fear conditioning. On the other hand, pre-recall administration of D-cycloserine -a positive modulator of NMDA sites capable of reverting memory resistance to pharmacological interference-, facilitated the increase of Lys-48 polyubiquitinated proteins in stressed animals. In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to further characterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling, protein degradation and memory destabilization in stress-induced resistant memories.
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Complexo Nuclear Basolateral da Amígdala/metabolismo , Condicionamento Clássico/fisiologia , Medo , Consolidação da Memória/fisiologia , Rememoração Mental/fisiologia , Estresse Psicológico/metabolismo , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Ciclosserina/farmacologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Consolidação da Memória/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Poliubiquitina/metabolismo , Ratos , Ubiquitinação/efeitos dos fármacosRESUMO
Upon retrieval, an aversive memory can undergo destabilization and reconsolidation. A traumatic-like memory, however, may be resistant to this process. The present study sought to contribute with a strategy to overcome this potential issue by investigating whether generalized fear retrieval is susceptible to destabilization-reconsolidation that can be pharmacologically modified. We hypothesized that exposure to a context that elicits moderate generalization levels would allow a malleable memory state. We developed a fear conditioning protocol in context A (cxt-A) paired with yohimbine administration to promote significant fear to a non-conditioned context B (cxt-B) in rats, mimicking the enhanced noradrenergic activity reported after traumatic events in humans. Next, we attempted to impair the reconsolidation phase by administering clonidine (CLO) immediately after exposure to cxt-A, cxt-B, or a third context C (cxt-C) neither conditioned nor generalized. CLO administered post-cxt-B exposure for two consecutive days subsequently resulted in decreased freezing levels in cxt-A. CLO after cxt-B only once, after cxt-A or cxt-C in two consecutive days, or independently of cxt-B exposures did not affect fear in a later test. A 6-h-delay in CLO treatment post-cxt-B exposures produced no effects, and nimodipine administered pre-cxt-B exposures precluded the CLO action. We then quantified the Egr1/Zif268 protein expression following cxt-B exposures and CLO treatments. We found that these factors interact to modulate this memory destabilization-reconsolidation mechanism in the basolateral amygdala but not the dorsal CA1 hippocampus. Altogether, memory destabilization can accompany generalized fear expression; thus, we may exploit it to potentiate reconsolidation blockers' action.
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Medo/psicologia , Generalização Psicológica , Consolidação da Memória/fisiologia , Memória/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Clonidina/farmacologia , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Proteína 1 de Resposta de Crescimento Precoce/genética , Extinção Psicológica , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Rememoração Mental , Ratos , Ratos Wistar , Simpatolíticos , IoimbinaRESUMO
BACKGROUND: Infection by Adenovirus 36 (Ad-36) has been associated with adipogenesis using cell and animal models, and a high risk of developing obesity has been reported in Ad-36-seropositive individuals. However, molecular mechanisms involved in the maintenance over the years of adipogenesis associated with Ad-36 has not been investigated in human adipose tissue. Epigenetic mechanisms, such as micro-RNAs (miRNAs) that regulate gene expression at the post-transcriptional level, have shown an important role in the development and maintenance of metabolic diseases. AIM: This study investigated the expression of miRNA associated with the adipogenic process in visceral adipose tissue from obese individuals according to Ad-36 serology. METHODS: Obese individuals were separated according to their status of Ad-36 serology in seropositive (Ad-36 (+); n = 29) and seronegative (Ad-36 (-); n = 28) groups. Additionally, a group of lean controls (n = 17) was selected to compare with obese individuals. Biopsies of visceral adipose tissue were obtained to evaluate miRNA and gene expression. The study of Ad-36 serology was carried out by ELISA. The expression of pro-adipogenic (miR-17 and miR-210) and anti-adipogenic (miR-155, miR-130 and miR-27a) miRNAs was evaluated using Taqman advanced miRNA assays by qPCR. The expression of adipogenes encoding LEP, ADIPOQ, and PPARγ was evaluated by Taqman predesigned assays through qPCR. RESULTS: The obese group had higher LEP (p < 0.001) and PPARγ (p = 0.016) expression and lower ADIPOQ expression (p = 0.017), and also had higher expression of miR-210 (p = 0.039), whereas lower expression of miR-155 (p = 0.019) and miR-27a (p = 0.028) as compared to lean controls. Higher PPARγ expression (p = 0.008), but no influence on LEP or ADIPOQ expression was observed in Ad-36 (+) group. Those seropositive individuals also had higher expression of the miR-17 (p = 0.028) and lower levels of miR-155 (p = 0.031) in adipose tissue as compared to seronegative subjects. CONCLUSIONS: Individuals with previous infection by Ad-36 had higher expression of the pro-adipogenic miR-17 and lower expression of the anti-adipogenic miR-155, which could lead to an increased adipogenic status by positively modulating PPARγ expression in adipose tissue from obese subjects.
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Adenoviridae/classificação , Gordura Intra-Abdominal/metabolismo , MicroRNAs/genética , Obesidade Mórbida/genética , Adulto , Estudos de Casos e Controles , Chile , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/virologia , PPAR gama/metabolismoRESUMO
Resumen El virus de la leucemia felina (ViLeF) es una de las principales enfermedades retrovirales de la familia Felidae que causan la muerte de sus individuos; de ahí interés diagnóstico y preventivo para la salud animal. El propósito de este artículo es determinar la prevalencia de infección por el ViLeF por serodiagnóstico del antígeno p27, en cuatro municipios del sur del valle de Aburrá, Colombia, usando los registros de los centros de diagnóstico del área. Se realizó un estudio descriptivo, transversal y retrospectivo, entre los años 2013-2015, que incluyó la revisión de 1718 pruebas diagnósticas de felinos domésticos del área urbana de Medellín, Envigado, Sabaneta y Caldas, procedentes de los centros de diagnóstico clínico del valle de Aburrá. El diagnóstico de ViLeF se realizó en muestras de suero por el inmunoensayo comercial Elisa (Idexx Laboratories©, Snap Combo Plus®, Maine, EUA). Los datos se procesaron en Statgraphics Centurión XVy se realizaron las pruebas estadísticas de Ji2 y Tukey. Del total de muestras, 376 (21,89 %) fueron positivas a la presencia del antígeno p27 de ViLeF. La edad de infectados osciló entre los 2 a 36 meses, hubo una mayor prevalencia en raza doméstica de pelo corto (DPC) y en machos. El porcentaje la prevalencia de ViLeF en el estudio fue de 21,88 %, siendo de importancia epidemiológica en el sur del Valle de Aburrá, Antioquia, Colombia.
Abstract Feline Leukemia Virus (FeLV) is one of the main retrovirus diseases of the Felidae family causing the death to the subjects. Therefore, there is a diagnostic and preventive interest regarding the animal health. This article aims to determine the infection prevalence due to FeLV after a p27 antigen serodiagnostic test applied in four towns in the southern Valle del Aburrá, Colombia, using the records of the diagnostic centers in each area. A descriptive, cross-sectional and retrospective study was conducted for the period 2013-2015, in which 1718 diagnostic tests from home felines were reviewed. These cases were from the urban area of Medellín, Envigado, Sabaneta and Caldas making part in the clinical diagnostic centers of the Valle de Aburrá. The FeLV diagnosis was conducted in serum samples with commercial immunoessay ELISA (IDEXX Laboratories©, Snap Combo Plus®, Maine, EUA). Data were processed in Statgraphics Centurión XV and statistical tests Ji2 and Tukey were conducted. Out of the total samples, 376 (21.89 %) were positive to p27 antigen for FeLV. The infected animals were from 2 to 36 months old. There was a higher prevalence among home races with short hair (SHR) and males. The FeLV prevalence percentage in the study was 21.88%, a figure with epidemiological significance in the southern Valle de Aburrá, Antioquia Province, Colombia.
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Resumen: En los últimos años la ecografía a la cabecera del paciente ha crecido exponencialmente. Su aplicación es observada en el quirófano, en las unidades de cuidados intensivos, en urgencias, en la atención de primer nivel e incluso en el trabajo de campo. Es tan versátil que facilita el diagnóstico, mejora la monitorización de los pacientes y apoya en los procedimientos invasivos, todo esto de forma segura y eficaz. En el área de la educación médica ha permeado hasta el pregrado, donde ya se le propone como una herramienta didáctica que permite la vinculación entre el conocimiento de las ciencias básicas y la aplicación clínica. La ecografía corresponde a uno de los instrumentos más versátiles en la medicina contemporánea, por lo que se hace obligada y prioritaria una mayor capacitación e investigación en el tema.
Abstract: In recent years, ultrasound at the patient's bedside has exponentially grown. Its application has been observed in the operating room, intensive care units, emergency rooms, first-level care and even in field work. It is so versatile that it facilitates diagnosis, improves patient monitoring and supports invasive procedures, all in a safe and effective manner. It has been used as a didactic tool in medical education that helps create a link between basic sciences and clinical application. Ultrasound is one of the most versatile instruments in contemporary medicine, hence, more training and research in the subject is a must and a priority.
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BACKGROUND: Adenovirus 36 (Ad-36) has been associated to adiposity in animal and in vitro studies. Ad-36 seropositivity has also been reported to contribute to obesity risk in children and adult populations. We investigated the relationship of Ad-36 serology with obesity and metabolic parameters in a Chilean population. SUBJECTS AND METHODS: Clinical and anthropometric data were obtained and blood samples were drawn from 99 lean (BMI: 18.5-24.9 kg/m2) and 151 obese (BMI > 30 kg/m2) subjects. Laboratory tests included lipid profile as well as glucose, insulin, leptin, and adiponectin levels. Ad-36 seropositivity was evaluated in serum samples by enzyme-linked immunosorbent assay. RESULTS: Seroprevalence of Ad-36 was higher in the obese group (58%) than in lean controls (34%) demonstrating that individuals previously infected with Ad-36 have higher risk of obesity in the study population (OR: 2.67, 95%CI: 1.58-4.51, p < 0.001). Interestingly, Ad-36 was related to lower concentrations of triglycerides and VLDL cholesterol in lean subjects (p = 0.049) and lower leptin in obese individuals (p = 0.014). Previous Ad-36 infection was also related to lower glycemia, insulinemia, and HOMA-IR (p < 0.05) in obese subjects who were not under antidiabetic drugs. CONCLUSIONS: Our results provide evidence of the contribution of previous Ad-36 infection to an increased risk of obesity in adult Chilean population. Ad-36 seropositivity was also associated to lipid profile, glycemic control, and leptin levels in adult Chilean population.