Midbrain and cerebral inflammatory and glutamatergic adaptations during chronic hypercapnia in goats.
Brain Res
; 1724: 146437, 2019 12 01.
Article
en En
| MEDLINE
| ID: mdl-31494104
ABSTRACT
Cognitive impairment is associated with multiple human diseases that have in common chronic hypercapnia. However, the mechanisms leading to chronic hypercapnia-induced cognitive decline are not known. We have previously shown chronic hypercapnia through exposure to increased inspired CO2 (6% InCO2) in conscious goats caused an immediate (within hours) and sustained decline in cognitive performance during a shape discrimination test. Herein, within the same goats, we assessed markers of neuroinflammation and glutamate receptor expression/phosphorylation within CNS regions important for cognitive function following 24â¯hours (h) or 30â¯days (d) of chronic hypercapnia. Within 24â¯h, chronic hypercapnia increased expression of the inflammatory cytokine IL-1ß in the orbitofrontal cortex and medial prefrontal cortex, but at 30d IL-1ß levels were not different relative to time-matched goats exposed to room-air. Additionally, Iba1 expression (a marker of microglial activation) was unaltered by chronic hypercapnia in all regions tested. Finally, levels of the total and phosphorylated AMPA receptor subunit GluR2 were reduced within the hippocampus at both 24â¯h and 30â¯d of hypercapnia, and reduced following 30â¯d within the anterior insular cortex. These data suggest that chronic hypercapnia leads to CNS site-dependent acute inflammatory responses and shifts in select glutamate receptor expression/phosphorylation in brain regions contributing to cognitive function. Such changes may be indicative of alterations in glutamatergic receptor-mediated signaling and neuronal dysfunction that contribute to declines in cognitive function associated with human diseases defined or marked by chronic CO2 retention.
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Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Mesencéfalo
/
Ácido Glutámico
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Hipercapnia
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos