Persistent suppression of phrenic motor plasticity after mild acute systemic inflammation in adult rats
Year: 2026
Type: article
Abstract: Inflammation, which is commonly associated with lung and neurological disorders, undermines a form of spinal serotonin-dependent respiratory motor plasticity elicited by moderate acute intermittent hypoxia (mAIH), known as phrenic long-term facilitation (pLTF). In adult rats, pLTF suppression has been studied 24 h following exposure to low-dose lipopolysaccharide (LPS) or 8 h of intermittent hypoxia simulating sleep apnea. In this timeframe, pLTF is suppressed by an adenosine 2 A (A2a) receptor and p38 MAP kinase-dependent mechanism. However, the duration of plasticity suppression following acute inflammation is unknown. We hypothesized that pLTF recovers when neuroinflammatory molecules return to normal. Thus, in Sprague Dawley rats, we assessed pLTF, ventral spinal (C3-C6) adenosine, and proinflammatory molecules after LPS (100 µg/kg ip). LPS increased spinal adenosine and microglial inflammatory genes at 24 h, but not 1 wk after LPS. Regardless, mAIH-induced pLTF remained suppressed for 3 wk, and then slowly recovered between 3 and 5 wk after LPS. Thus, pLTF suppression outlasts active inflammation. Contrary to 24 hours, at 1 wk after LPS, spinal A2a receptor inhibition (MSX-3) failed to restore pLTF, whereas spinal p38 MAPK inhibition (SB202190) rescued pLTF at both 24 hours and 1 wk after LPS. These findings suggest that distinct mechanisms underlie pLTF suppression at 24 h versus 1 wk after LPS, although both mechanisms share downstream p38 MAPK signaling. Since mAIH is emerging as a therapeutic modality to improve respiratory and nonrespiratory motor function in people with neurological disorders, targeting p38 MAPK may prevent persistent plasticity suppression in individuals with a history of inflammation.
Source: Function
Institution: University of Florida
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
OpenAlex ID: W7124431000