Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage

Area of Science:

• Developmental biology
• Neuroscience
• Pharmacology

Background:

• Beta-3 adrenergic receptor (β3-AR) expression is oxygen-dependent and crucial for organ maturation.
• β3-AR agonism has previously shown protective effects against hyperoxia-induced large bowel injury.
• Hyperoxia can negatively impact the developing enteric nervous system (ENS).

Purpose of the Study:

• To investigate the impact of β3-AR agonism on hyperoxia-induced alterations in the ileal ENS.
• To evaluate the therapeutic potential of BRL37344, a β3-AR agonist, in a rat model of neonatal hyperoxia.

Main Methods:

• Sprague-Dawley rat pups were exposed to normoxia or hyperoxia (85% oxygen) for two weeks.
• Pups received varying doses of the β3-AR agonist BRL37344 (1, 3, or 6 mg/kg).
• The effects on neuronal populations (nitrergic, cholinergic) and glial cells (S100β+, GFAP+) in the myenteric and submucosal plexuses were assessed.

Main Results:

• Hyperoxia disrupted the balance of nitrergic and cholinergic neurons in both ileal plexuses.
• Hyperoxia decreased submucosal neuron counts and myenteric glial cell populations (S100β+, GFAP+).
• Treatment with 3 mg/kg BRL37344 preserved neuronal chemical coding and partially protected myenteric glial cells but did not prevent submucosal neuronal loss.

Conclusions:

• Neonatal hyperoxia induces significant alterations in the ileal enteric nervous system.
• β3-AR agonism demonstrates a potential therapeutic benefit in mitigating some hyperoxia-induced ENS damage.
• Further research is warranted to explore β3-AR agonism as a strategy for protecting the developing gut from hyperoxia-related injury.