Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.

Autor:	Dickstein DL; Uniformed Services University of Health Sciences., Zhang R; University of California, Irvine School of Medicine., Ru N; University of California, Irvine School of Medicine., Vozenin MC; Hôpitaux Universitaires de Genève., Perry BC; Uniformed Services University of Health Sciences., Wang J; Uniformed Services University of Health Sciences., Baulch J; University of California, Irvine School of Medicine., Acharya MM; University of California, Irvine School of Medicine., Limoli CL; University of California, Irvine School of Medicine.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.21203/rs.3.rs-4656938/v1
Abstrakt:	Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) protects against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity of granule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. To explore the sensitivity of different neuronal populations to cranial irradiation and dose-rate modulation, hippocampal CA1 and medial prefrontal cortex (PFC) pyramidal neurons were analyzed by electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in PFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3×10Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are more radioresistant irrespective of radiation dose-rate. Competing Interests: Competing interests The authors have no relevant financial or non- financial interests to disclose.
Databáze:	MEDLINE
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