Abstract
HIGD1A (hypoxia-induced gene domain protein-1a), a mitochondrial inner membrane protein present in various cell types, has been mainly associated with anti-apoptotic processes in response to stressors. Our previous findings have shown that Higd1a mRNA is widely expressed across the central nervous system (CNS), exhibiting an increasing expression in the spinal cord from postnatal day 1 (P1) to 15 (P15) and changes in the distribution pattern from P1 to P90. During the first weeks of postnatal life, the great plasticity of the CNS is accompanied by cell death/survival decisions. So we first describe HIGD1A expression throughout the brain during early postnatal life in female and male pups. Secondly, based on the fact that in some areas this process is influenced by the sex of individuals, we explore HIGD1A expression in the sexual dimorphic nucleus (SDN) of the medial preoptic area, a region that is several folds larger in male than in female rats, partly due to sex differences in the process of apoptosis during this period. Immunohistochemical analysis revealed that HIGD1A is widely but unevenly expressed throughout the brain. Quantitative Western blot analysis of the parietal cortex, diencephalon, and spinal cord from both sexes at P1, P5, P8, and P15 showed that the expression of this protein is predominantly high and changes with age but not sex. Similarly, in the sexual dimorphic nucleus, the expression of HIGD1A varied according to age, but we were not able to detect significant differences in its expression according to sex. Altogether, these results suggest that HIGD1A protein is expressed in several areas of the central nervous system following a pattern that quantitatively changes with age but does not seem to change according to sex.
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Acknowledgments
The authors wish to thank Héctor Rodríguez, Joel González and Enzo Cavelli for their excellent animal care, Dr. Inés Pose for assistance in histological analysis, and Dr. Adriana Parodi for her helpful advice.
Funding
This work was supported in part by the Agencia Nacional de Investigación e Innovación (ANII) of Uruguay (grant number FCE_2_2011_1_6459) and Comisión Sectorial de Investigación Científica (Universidad de la República, Uruguay).
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Animal care and experimental procedures were performed in accordance with the Uruguayan law (Law No. 18611) on the use and care of laboratory animals, and the Ethical Committee of Facultad de Ciencias approved this study (exp.240011-002308-14).
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Representative photomicrographs of immunohistochemical DAB staining of HIGD1A in male and female P8 brain regions, corresponding to cited in Table 1.
ESM 1
Immunohistochemical distribution of HIGD1A protein in telencephalon regions. (PNG 5482 kb)
ESM 2
Immunohistochemical distribution of HIGD1A protein in diencephalon regions. (PNG 2825 kb)
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López, L., Zuluaga, M.J., Lagos, P. et al. The Expression of Hypoxia-Induced Gene 1 (Higd1a) in the Central Nervous System of Male and Female Rats Differs According to Age. J Mol Neurosci 66, 462–473 (2018). https://doi.org/10.1007/s12031-018-1195-y
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DOI: https://doi.org/10.1007/s12031-018-1195-y