NDLI: Whole-brain irradiation differentially modifies neurotransmitters levels and receptors in the hypothalamus and the prefrontal cortex

Content Provider	Springer Nature : BioMed Central
Author	Franco-Pérez, Javier Montes, Sergio Sánchez-Hernández, Josué Ballesteros-Zebadúa, Paola
Abstract	Background Whole-brain radiotherapy is a primary treatment for brain tumors and brain metastasis, but it also induces long-term undesired effects. Since cognitive impairment can occur, research on the etiology of secondary effects has focused on the hippocampus. Often overlooked, the hypothalamus controls critical homeostatic functions, some of which are also susceptible after whole-brain radiotherapy. Therefore, using whole-brain irradiation (WBI) in a rat model, we measured neurotransmitters and receptors in the hypothalamus. The prefrontal cortex and brainstem were also analyzed since they are highly connected to the hypothalamus and its regulatory processes. Methods Male Wistar rats were exposed to WBI with 11 Gy (Biologically Effective Dose = 72 Gy). After 1 month, we evaluated changes in gamma-aminobutyric acid (GABA), glycine, taurine, aspartate, glutamate, and glutamine in the hypothalamus, prefrontal cortex, and brainstem according to an HPLC method. Ratios of Glutamate/GABA and Glutamine/Glutamate were calculated. Through Western Blott analysis, we measured the expression of GABAa and GABAb receptors, and NR1 and NR2A subunits of NMDA receptors. Changes were analyzed comparing results with sham controls using the non-parametric Mann–Whitney U test (p < 0.05). Results WBI with 11 Gy induced significantly lower levels of GABA, glycine, taurine, aspartate, and GABAa receptor in the hypothalamus. Also, in the hypothalamus, a higher Glutamate/GABA ratio was found after irradiation. In the prefrontal cortex, WBI induced significant increases of glutamine and glutamate, Glutamine/Glutamate ratio, and increased expression of both GABAa receptor and NMDA receptor NR1 subunit. The brainstem showed no statistically significant changes after irradiation. Conclusion Our findings confirm that WBI can affect rat brain regions differently and opens new avenues for study. After 1 month, WBI decreases inhibitory neurotransmitters and receptors in the hypothalamus and, conversely, increases excitatory neurotransmitters and receptors in the prefrontal cortex. Increments in Glutamate/GABA in the hypothalamus and Glutamine/Glutamate in the frontal cortex indicate a neurochemical imbalance. Found changes could be related to several reported radiotherapy secondary effects, suggesting new prospects for therapeutic targets.
Related Links	https://ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-020-01716-y.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13014-020-01716-y
Journal	Radiation Oncology
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2020-11-23
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Radiotherapy Imaging Radiology Whole brain irradiation Amino acids Neurotransmitters Prefrontal cortex Hypothalamus GABAa GABAb NR1 NR2A
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Oncology
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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