TY - JOUR
T1 - Fluoxetine exposure throughout neurodevelopment differentially influences basilar dendritic morphology in the motor and prefrontal cortices
AU - Maloney, Susan E.
AU - Tabachnick, Dora R.
AU - Jakes, Christine
AU - Avdagic, Selma
AU - Bauernfeind, Amy L.
AU - Dougherty, Joseph D.
N1 - Funding Information:
This work was funded by W.M. Keck Fellowship in Molecular Medicine from Washington University in St. Louis (SEM), and the NIH (P50 HD103525, IDDRC@WUSTL).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The significance of serotonin (5HT) in mental health is underscored by the serotonergic action of many classes of psychiatric medication. 5HT is known to have a significant role in neurodevelopment, thus 5HT disruption during development may have a long term impact on brain structure and circuits. We previously generated a model of 5HT alteration throughout neurodevelopment by maternal administration of the selective serotonin reuptake inhibitor fluoxetine. We found resulting social behavior alterations in the offspring during both postnatal and adult ages. Previous work by others has indicated that early 5HT disruption influences neuronal morphology. Therefore, in the current study we sought to determine if dendritic morphological changes occur in areas involved in the social behavior deficits we previously observed, specifically the primary motor (M1) and medial prefrontal (mPFC) cortices. We quantified dendritic morphology of projection neurons in M1 and mPFC at postnatal day (P)10 and P79 in mice exposed to fluoxetine. Basilar dendritic complexity and spine density were persistently decreased in M1 fluoxetine-exposed neurons while in the mPFC, similar reductions were observed at P79 but were not present at P10. Our findings underscore that the developing brain, specifically the projection cortex, is vulnerable to 5HT system perturbation, which may be related to later behavioral disruptions.
AB - The significance of serotonin (5HT) in mental health is underscored by the serotonergic action of many classes of psychiatric medication. 5HT is known to have a significant role in neurodevelopment, thus 5HT disruption during development may have a long term impact on brain structure and circuits. We previously generated a model of 5HT alteration throughout neurodevelopment by maternal administration of the selective serotonin reuptake inhibitor fluoxetine. We found resulting social behavior alterations in the offspring during both postnatal and adult ages. Previous work by others has indicated that early 5HT disruption influences neuronal morphology. Therefore, in the current study we sought to determine if dendritic morphological changes occur in areas involved in the social behavior deficits we previously observed, specifically the primary motor (M1) and medial prefrontal (mPFC) cortices. We quantified dendritic morphology of projection neurons in M1 and mPFC at postnatal day (P)10 and P79 in mice exposed to fluoxetine. Basilar dendritic complexity and spine density were persistently decreased in M1 fluoxetine-exposed neurons while in the mPFC, similar reductions were observed at P79 but were not present at P10. Our findings underscore that the developing brain, specifically the projection cortex, is vulnerable to 5HT system perturbation, which may be related to later behavioral disruptions.
UR - http://www.scopus.com/inward/record.url?scp=85129556623&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-11614-w
DO - 10.1038/s41598-022-11614-w
M3 - Article
C2 - 35534532
AN - SCOPUS:85129556623
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 7605
ER -