NMR based metabolomics reveals acute hippocampal metabolic fluctuations during cranial irradiation in murine model.
Cranial irradiation is widely used as a treatment modality or prophylactic treatment in cancer patients, but it is frequently related to neurocognitive impairment in cancer survivors. Though most of radiation-induced changes occur during early and late delayed phase of radiation sickness, recent reports have supported the evidence of impaired neurogenesis within 24-48 h of radiation exposure that may implicate changes in acute phase as well. Inspection of these acute changes could be considered important as they may have long lasting effect on cognitive development and functions. In the present study, (1)H NMR spectroscopy based metabolomic approach was used to obtain comprehensive information of hippocampus metabolic physiology during acute phase of radiation sickness in a mouse model for single dose 8 Gy cranial irradiation. The analysis demonstrated reduced metabolic activity in irradiated animals compared to controls, typically evident in citric acid cycle intermediates, glutamine/glutamate and ketone bodies metabolism thus providing strong indication that the hippocampus is metabolically responsive to radiation exposure. The data suggested reduced glucose utilization, altered intermediary and neurotransmitter metabolism in hippocampus tissue extract. To the best of our knowledge this is the first metabolomic study to document cranial irradiation induced acute metabolic changes using in vitro(1)H NMR spectroscopy.
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Poonam
P
Rana
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Mamta
M
Gupta
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Ahmad Raza
AR
Khan
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
B S
BS
Hemanth Kumar
Centre for Biomedical Magnetic Resonance (CBMR), SGPGIMS Campus, Lucknow, Uttar Pradesh, India.
Raja
R
Roy
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India. Electronic address: skhushu@yahoo.com.
Subash
S
Khushu
D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D055432:Metabolomics; D051379:Mice; D066244:Proton Magnetic Resonance Spectroscopy
Cranial radiation; Hippocampus; Intermediary metabolism; NMR spectroscopy