Mutation of Brain Aromatase Impairs Behavior and Neuroplasticity in Adult Zebrafish
Brain aromatase, an enzyme responsible for the local synthesis of estrogens, plays a key role in regulating behavior and neuroplasticity in mammals. In teleost fish, brain aromatase is encoded by the
cyp19a1b
gene, which is strongly expressed in radial glial cells; however, the specific functions of this enzyme are currently unknown. To investigate its role, a
cyp19a1b
‐mutant zebrafish line was generated using gene‐editing techniques. Behavioral, neurogenic, and neurotransmission‐related parameters were assessed in adult male and female zebrafish. Behavioral analysis highlighted significant alterations in mutant zebrafish, including changes in swimming activity, boldness, sociability, and aggression, with a stronger effect in males compared to females. Beyond these behavioral modifications, mutant zebrafish exhibited disrupted cell proliferation patterns, as assessed by PCNA immunofluorescence in key forebrain regions. Specifically, proliferation decreased in the telencephalon and in the caudal hypothalamus of mutant zebrafish while increasing in the olfactory bulbs. The number of dopaminergic and serotonergic neurons, visualized by immunofluorescence, remained unchanged. Similarly, HPLC‐ED quantification of monoamines and their metabolites showed no significant differences between mutant and wild‐type zebrafish. To further explore the impact of the
cyp19a1b
mutation on gene expression, transcriptomic analysis was performed using BRB‐Seq technology. Gene expression analyses identified several processes affected by the mutation, including cell proliferation, apoptosis, estrogen signaling, neuroplasticity, and behavioral regulation, in a sex‐ and region‐dependent manner. In conclusion, our results demonstrate that several behaviors, including locomotor activity, sociability, aggressiveness, and anxiety, exhibit marked sexual dimorphism. They show that the
cyp19a1b
mutation affects locomotor activity in a context‐dependent manner, increases boldness, and reduces aggressiveness. In addition, transcriptomic analyses revealed widespread dysregulation of gene expression, which likely contributes to the observed behavioral alterations. Taken together, these findings underscore the crucial role of brain aromatase in the neurobiological regulation of diverse behaviors.
image
No keywords indexed for this article. Browse by subject →
Jennifer L. Anderson, Timothy S. Mulligan, Meng-Chieh Shen et al.
Lin S. Huffman, Lauren A. O’Connell, Hans A. Hofmann
Showing 50 of 97 references
- Published
- Aug 01, 2025
- Vol/Issue
- 169(8)
- License
- View
You May Also Like
A. H. V. Schapira, J. M. Cooper · 1990
1,684 citations
Lasse K. Bak, Arne Schousboe · 2006
975 citations
Yuanbin Liu, Daniel A. Peterson · 1997
814 citations