TY  - JOUR
AU  - Jukić, Marin
AU  - Carrillo-Roa, T
AU  - Bar, M
AU  - Becker, G
AU  - Jovanović, V.M
AU  - Zega, K
AU  - Binder, E.B
AU  - Brodski, C
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2488
AB  - Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressing Otx2 in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic-and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT 2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with schizophrenia or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD.
PB  - Nature Publishing Group
T2  - Neuropsychopharmacology
T1  - Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder
VL  - 40
IS  - 4
SP  - 839
EP  - 848
DO  - 10.1038/npp.2014.244
ER  - 

@article{
author = "Jukić, Marin and Carrillo-Roa, T and Bar, M and Becker, G and Jovanović, V.M and Zega, K and Binder, E.B and Brodski, C",
year = "2015",
abstract = "Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressing Otx2 in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic-and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT 2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with schizophrenia or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD.",
publisher = "Nature Publishing Group",
journal = "Neuropsychopharmacology",
title = "Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder",
volume = "40",
number = "4",
pages = "839-848",
doi = "10.1038/npp.2014.244"
}

Jukić, M., Carrillo-Roa, T., Bar, M., Becker, G., Jovanović, V.M, Zega, K., Binder, E.B,& Brodski, C.. (2015). Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder. in Neuropsychopharmacology
Nature Publishing Group., 40(4), 839-848.
https://doi.org/10.1038/npp.2014.244

Jukić M, Carrillo-Roa T, Bar M, Becker G, Jovanović V, Zega K, Binder E, Brodski C. Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder. in Neuropsychopharmacology. 2015;40(4):839-848.
doi:10.1038/npp.2014.244 .

Jukić, Marin, Carrillo-Roa, T, Bar, M, Becker, G, Jovanović, V.M, Zega, K, Binder, E.B, Brodski, C, "Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder" in Neuropsychopharmacology, 40, no. 4 (2015):839-848,
https://doi.org/10.1038/npp.2014.244 . .