ArticleScientific reports2018
Serotonin depletion causes valproate-responsive manic-like condition and increased hippocampal neuroplasticity that are reversed by stress.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
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- Treadmill exercise alleviates depression in female mice induced by chronic unpredictable mild stress through the Inhibition of cGAS-STING signalling.Scientific reports · 2025Article
- Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Antidepressants in Bipolar Depression: From Neurotransmitter Mechanisms to Clinical Challenges.Actas espanolas de psiquiatria · 2025Review
- Socio-affective communication in Tph2-deficient rat pups: communal nesting aggravates growth retardation despite ameliorating maternal affiliation deficits.Molecular autism · 2024Article
- Impact of Serotonin Deficiency on Circadian Dopaminergic Rhythms.International journal of molecular sciences · 2024Article
- Difference between Quantitative Electroencephalography, Loudness Dependence of Auditory Evoked Potential, and Mismatch Negativity between a Manic and a Depressive Episode in a Single Bipolar Patient with Mixed Features.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2024Article
- Serotonin drives aggression and social behaviors of laboratory male mice in a semi-natural environment.Frontiers in behavioral neuroscience · 2024Article
- Wiring and Volume Transmission: An Overview of the Dual Modality for Serotonin Neurotransmission.ACS chemical neuroscience · 2023Review
- Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.International journal of molecular sciences · 2023Review
- Predicting the distribution of serotonergic axons: a supercomputing simulation of reflected fractional Brownian motion in a 3D-mouse brain model.Frontiers in computational neuroscience · 2023Article
- D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans.Translational psychiatry · 2022Article
- Slitrk2 deficiency causes hyperactivity with altered vestibular function and serotonergic dysregulation.iScience · 2022Article
- Fluoxetine exposure throughout neurodevelopment differentially influences basilar dendritic morphology in the motor and prefrontal cortices.Scientific reports · 2022Article
- High-resolution spatiotemporal analysis of single serotonergic axons in anFrontiers in neuroscience · 2022Article
- A new molecular risk pathway for postpartum mood disorders: clues from steroid sulfatase-deficient individuals.Archives of women's mental health · 2021Review
- TRPM3 in Brain (Patho)Physiology.Frontiers in cell and developmental biology · 2021Review
- Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine DiScience · 2020Article
- Embracing diversity in the 5-HT neuronal system.Nature reviews. Neuroscience · 2019Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal hippocampal neural plasticity has been implicated in behavioural abnormalities and complex neuropsychiatric conditions, including bipolar disorder (BD). However, the determinants of this neural alteration remain unknown. This work tests the hypothesis that the neurotransmitter serotonin (5-HT) is a key determinant of hippocampal neuroplasticity, and its absence leads to maladaptive behaviour relevant for BD. Depletion of brain 5-HT in Tph2 mutant mice resulted in reduced behavioural despair, reduced anxiety, marked aggression and lower habituation in novel environments, reminiscent of bipolar-associated manic behaviour. Treatment with valproate produced a substantial improvement of the mania-like behavioural phenotypes displayed by Tph2 mutants. Brain-wide fMRI mapping in mutants revealed functional hippocampal hyperactivity in which we also observed dramatically increased neuroplasticity. Importantly, remarkable correspondence between the transcriptomic profile of the Tph2 mutant hippocampus and neurons from bipolar disorder patients was observed. Chronic stress reversed the emotional phenotype and the hippocampal transcriptional landscape of Tph2 mutants. These changes were associated with inappropriate activation of transcriptional adaptive response to stress as assessed by gene set enrichment analyses in the hippocampus of Tph2 mutant mice. These findings delineate 5-HT as a critical determinant in BD associated maladaptive emotional responses and aberrant hippocampal neuroplasticity, and support the use of Tph2-/- mice as a new research tool for mechanistic and therapeutic research in bipolar disorder.
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