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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Claudia Rangel-Barajas1,2, Abigail Perkins1, Dalia Elkhatib1

  • 1Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Alzheimer

Palabras clave:
ratonesAlzheimerpatologíagenéticametabolismosinapsiscerebrotransgénicohumanosApolipoproteína E4Proteína Disks Large Homolog 4macho

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Área de la Ciencia:

  • Neurociencia; Genética; Biología Molecular

Sus antecedentes:

  • La enfermedad de Alzheimer (AD) es un trastorno neurodegenerativo caracterizado por el deterioro cognitivo y la degeneración sináptica.
  • La pérdida sináptica es un indicador clave del deterioro cognitivo en la AD, que puede preceder a la formación de placas amiloides.
  • La investigación de la integridad sináptica en modelos de ratones genéticamente modificados es crucial para comprender la patogénesis de la AD.

Objetivo del estudio:

  • Evaluar la integridad sináptica y los perfiles transcriptómicos en ratones LOAD2, un modelo que porta factores de riesgo genético humanizados para la enfermedad de Alzheimer de inicio tardío (LOAD).
  • Identificar alteraciones dependientes de la edad en proteínas sinápticas y expresión génica relevantes para la patología de la AD.
  • Evaluar la utilidad del modelo de ratón LOAD2 para estudiar la progresión de la LOAD.

Principales métodos:

  • Aislamiento de fracciones subcelulares de cerebros de ratones LOAD2 para analizar componentes sinápticos y extrasinápticos.
  • Análisis de Western blot para evaluar la expresión de proteínas de estructura y función sináptica en diferentes edades.
  • Hibridación de ácidos nucleicos multiplex Nanostring para el perfilado genético integral para detectar cambios en la expresión.

Principales resultados:

  • Los ratones LOAD2 exhibieron cambios significativos dependientes de la edad en las proteínas presinápticas SV2A y bassoon.
  • Se observaron alteraciones en la composición de la subunidad del receptor NMDA y AMPA en los sitios postsinápticos.
  • La neurogranina, un marcador disminuido en el LCR de pacientes con AD, se redujo significativamente en los ratones LOAD2.

Conclusiones:

  • El modelo de ratón LOAD2, desarrollado con factores de riesgo genético humanizados, muestra alteraciones en las proteínas sinápticas que reflejan la patología de la AD humana.
  • Estos hallazgos validan el modelo LOAD2 para el estudio de los cambios sinápticos en la enfermedad de Alzheimer de inicio tardío.
  • La integridad sináptica y las firmas moleculares en los ratones LOAD2 se asemejan estrechamente a las observadas en la AD humana.