Cranial radiotherapy profoundly affects glia without inducing widespread cellular senescence

Area of Science:

• Neuroscience
• Oncology
• Gerontology

Background:

• Cranial radiotherapy is linked to cognitive deficits in cancer patients, potentially due to accelerated brain aging.
• Radiotherapy is known to induce cellular senescence, a state of irreversible cell cycle arrest, in tumors and in vitro.
• This study investigated whether cranial radiotherapy induces cellular senescence in the brain.

Purpose of the Study:

• To determine if cranial radiotherapy induces cellular senescence in the brain.
• To investigate the effects of cranial radiotherapy on glial cells.
• To compare radiotherapy-induced brain changes with natural aging processes.

Main Methods:

• Male C57BL/6 mice were subjected to fractionated CT-guided cranial radiotherapy at various dosages.
• Brain tissue was analyzed for senescence and glial markers using immunohistochemistry, histochemistry, Cosmx SMI, and RT-qPCR.
• Brains from aged mice (77 weeks old) were studied to compare radiotherapy effects with natural aging.

Main Results:

• Cranial radiotherapy did not increase markers of cellular senescence in the brain.
• Profound changes were observed in different types of glia following cranial radiotherapy.
• Aged mice showed similar glial changes, though milder, without increased senescence markers.

Conclusions:

• Cellular senescence appears uncommon in the healthy brain and is not induced by cranial radiotherapy.
• Cranial radiotherapy significantly alters glial cells in the brain.
• These glial changes may be relevant to the cognitive problems experienced by patients after radiotherapy.