TY - JOUR

T1 - Early adolescence prefrontal cortex alterations in female rats lacking dopamine transporter

AU - Illiano, Placido

AU - Leo, Damiana

AU - Gainetdinov, Raul R.

AU - Pardo, Marta

N1 - Illiano, P.; Leo, D.; Gainetdinov, R.R.; Pardo, M. Early Adolescence Prefrontal Cortex Alterations in Female Rats Lacking Dopamine Transporter. Biomedicines 2021, 9, 157. https://doi.org/10.3390/biomedicines9020157

PY - 2021/2/5

Y1 - 2021/2/5

N2 - Monoamine dysfunctions in the prefrontal cortex (PFC) can contribute to diverse neuropsy-chiatric disorders, including ADHD, bipolar disorder, PTSD and depression. Disrupted dopamine (DA) homeostasis, and more specifically dopamine transporter (DAT) alterations, have been reported in a variety of psychiatric and neurodegenerative disorders. Recent studies using female adult rats heterozygous (DAT+/−) and homozygous (DAT−/−) for DAT gene, showed the utility of those rats in the study of PTSD and ADHD. Currently, a gap in the knowledge of these disorders affecting adolescent females still represents a major limit for the development of appropriate treatments. The present work focuses on the characterization of the PFC function under conditions of heterozygous and homozygous ablation of DAT during early adolescence based on the known implication of DAT and PFC DA in psychopathology during adolescence. We report herein that genetic ablation of DAT in the early adolescent PFC of female rats leads to changes in neuronal and glial cell homeostasis. In brief, we observed a concurrent hyperactive phenotype, accompanied by PFC alterations in glu-tamatergic neurotransmission, signs of neurodegeneration and glial activation in DAT-ablated rats. The present study provides further understanding of underlying neuroinflammatory pathological processes that occur in DAT-ablated female rats, what can provide novel investigational approaches in human diseases.

AB - Monoamine dysfunctions in the prefrontal cortex (PFC) can contribute to diverse neuropsy-chiatric disorders, including ADHD, bipolar disorder, PTSD and depression. Disrupted dopamine (DA) homeostasis, and more specifically dopamine transporter (DAT) alterations, have been reported in a variety of psychiatric and neurodegenerative disorders. Recent studies using female adult rats heterozygous (DAT+/−) and homozygous (DAT−/−) for DAT gene, showed the utility of those rats in the study of PTSD and ADHD. Currently, a gap in the knowledge of these disorders affecting adolescent females still represents a major limit for the development of appropriate treatments. The present work focuses on the characterization of the PFC function under conditions of heterozygous and homozygous ablation of DAT during early adolescence based on the known implication of DAT and PFC DA in psychopathology during adolescence. We report herein that genetic ablation of DAT in the early adolescent PFC of female rats leads to changes in neuronal and glial cell homeostasis. In brief, we observed a concurrent hyperactive phenotype, accompanied by PFC alterations in glu-tamatergic neurotransmission, signs of neurodegeneration and glial activation in DAT-ablated rats. The present study provides further understanding of underlying neuroinflammatory pathological processes that occur in DAT-ablated female rats, what can provide novel investigational approaches in human diseases.

KW - Adolescence

KW - Dopamine transporter

KW - Knockout

KW - Neurodegeneration

KW - Neuroinflamma-tion

KW - Prefrontal cortex

UR - http://www.scopus.com/inward/record.url?scp=85100791736&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/6324692b-d528-3628-93c2-6929e3ac0027/

U2 - 10.3390/biomedicines9020157

DO - 10.3390/biomedicines9020157

M3 - Article

AN - SCOPUS:85100791736

VL - 9

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 2

M1 - 157

ER -