Oral and Injected Tamoxifen Alter Adult Hippocampal Neurogenesis in Female and Male Mice.

Autor:	Smith BM; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210., Saulsbery AI; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210., Sarchet P; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210., Devasthali N; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210., Einstein D; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210., Kirby ED; Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH 43210 kirby.224@osu.edu.; Chronic Brain Injury Initiative, The Ohio State University, Columbus, OH 43210.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2022 Apr 20; Vol. 9 (2). Date of Electronic Publication: 2022 Apr 20 (Print Publication: 2022).
DOI:	10.1523/ENEURO.0422-21.2022
Abstrakt:	Inducible Cre recombinase facilitates temporal control of genetic recombination in numerous transgenic model systems, a feature which has made it a popular tool for adult neurogenesis studies. One of the most common forms of inducible Cre, CreER T2 , requires activation by the selective estrogen receptor modulator tamoxifen (TAM) to initiate recombination of LoxP-flanked sequences. To date, most studies deliver TAM via intraperitoneal injection. But the introduction of TAM-infused commercial chows has recently expanded the possible modes of TAM delivery. Despite the widespread use of TAM-inducible genetic models in adult neurogenesis research, the comparative efficiency and off-target effects of TAM administration protocols is surprisingly infrequently studied. Here, we compare a standard, 5 d TAM injection regimen with voluntary consumption of TAM-infused chow. First, we used adult NestinCreER T2 ;Rosa-LoxP-STOP-LoxP-EYFP reporter mice to show that two weeks of TAM chow and 5 d of injections led to LoxP recombination in a similar phenotypic population of neural stem and progenitor cells (NSPCs) in the adult dentate gyrus. However, TAM chow resulted in substantially less overall recombination than injections. TAM administration also altered adult neurogenesis, but in different ways depending on administration route: TAM injection disrupted neural progenitor cell proliferation three weeks after TAM, whereas TAM chow increased neuronal differentiation of cells generated during the diet period. These findings provide guidance for selection of TAM administration route and appropriate controls in adult neurogenesis studies using TAM-inducible Cre mice. They also highlight the need for better understanding of off-target effects of TAM in other neurologic processes and organ systems. (Copyright © 2022 Smith et al.)
Databáze:	MEDLINE
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