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Infection01:20

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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.
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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 (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.
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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

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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.
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Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Belay Gebregergis1,2, Liam T Ralph2, Liang Zhang1,3

  • 1University of Toronto, Toronto, ON, Canada.

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

La deficiencia de C9orf72 causa hiperexcitabilidad sináptica y excitotoxicidad en modelos de demencia frontotemporal. La focalización de receptores de AMPA permeables al calcio (CP-AMPAR) ofrece una estrategia terapéutica potencial para la neurodegeneración asociada a C9orf72.

Palabras clave:
ratonesdemencia frontotemporalC9orf72hiperexcitabilidad sinápticaexcitotoxicidadCP-AMPARneurodegeneraciónterapéutica

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Área de la Ciencia:

  • Neurociencia; Genética; Biología Celular

Sus antecedentes:

  • Las expansiones del gen C9orf72 son la principal causa genética de demencia frontotemporal (FTD) y esclerosis lateral amiotrófica (ELA). La deficiencia de C9orf72 está relacionada con disfunción sináptica y neurodegeneración, con la hiperexcitabilidad y la excitotoxicidad como signos emergentes. Los mecanismos precisos que subyacen a estos déficits en la patología de la demencia no se comprenden completamente.

Objetivo del estudio:

  • Investigar el papel de C9orf72 en la función sináptica y la vulnerabilidad excitotóxica utilizando un modelo de ratón. Explorar la participación de los receptores AMPA permeables al calcio (CP-AMPAR) en la neurodegeneración asociada a C9orf72. Evaluar el potencial terapéutico de los antagonistas de CP-AMPAR.

Principales métodos:

  • Se utilizaron ratones C9orf72-knockout (C9-KO) para modelar la enfermedad. Se evaluaron marcadores sinápticos del hipocampo, morfología de espinas dendríticas y plasticidad mediada por CP-AMPAR. Se indujo estrés excitotóxico con ácido kainiico (KA) para analizar la susceptibilidad a convulsiones, la estabilidad de la red (EEG) y la expresión de GluA1, seguido de tratamiento con antagonistas de CP-AMPAR.

Principales resultados:

  • Los ratones C9-KO mostraron un aumento de la hiperexcitabilidad sináptica, evidenciado por un aumento de GluA1 en la superficie, una reducción de la densidad de espinas dendríticas y cabezas de espina agrandadas. Estos ratones exhibieron plasticidad mejorada de CP-AMPAR y mayor vulnerabilidad a la excitotoxicidad inducida por KA, incluyendo convulsiones severas y EEG anormal. El antagonismo selectivo de CP-AMPAR mitigó con éxito el daño excitotóxico y restauró la función sináptica.

Conclusiones:

  • La deficiencia de C9orf72 exacerba la hiperexcitabilidad sináptica y la vulnerabilidad excitotóxica a través de la desregulación de CP-AMPAR, contribuyendo a la fisiopatología de la FTD. La pérdida de C9orf72 amplifica la señalización excitatoria, vinculando la disfunción sináptica con la inestabilidad de la red y la neurodegeneración. Los CP-AMPAR se identifican como mediadores clave de la excitotoxicidad, representando un objetivo terapéutico prometedor para las demencias relacionadas con C9orf72 y otros trastornos neurodegenerativos.