Dysfunction of the serotonergic system in the brain of synapsin triple knockout mice is associated with behavioral abnormalities resembling synapsin-related human pathologies.
Prog Neuropsychopharmacol Biol Psychiatry
; 105: 110135, 2021 03 08.
Article
em En
| MEDLINE
| ID: mdl-33058959
ABSTRACT
Synapsins (Syns) are a family of phosphoproteins associated with synaptic vesicles (SVs). Their main function is to regulate neurotransmitter release by maintaining a reserve pool of SVs at the presynaptic terminal. Previous studies reported that the deletion of one or more Syn genes in mice results in an epileptic phenotype and autism-related behavioral abnormalities. Here we aimed at characterizing the behavioral phenotype and neurobiological correlates of the deletion of Syns in a Syn triple knockout (TKO) mouse model. Wild type (WT) and TKO mice were tested in the open field, novelty suppressed feeding, light-dark box, forced swim, tail suspension and three-chamber sociability tests. Using in vivo electrophysiology, we recorded the spontaneous activity of dorsal raphe nucleus (DRN) serotonin (5-HT) and ventral tegmental area (VTA) dopamine (DA) neurons. Levels of 5-HT and DA in the frontal cortex and hippocampus of WT and TKO mice were also assessed using a High-Performance Liquid Chromatography. TKO mice displayed hyperactivity and impaired social and anxiety-like behavior. Behavioral dysfunctions were accompanied by reduced firing activity of DRN 5-HT, but not VTA DA, neurons. TKO mice also showed increased responsiveness of DRN 5-HT-1A autoreceptors, measured as a reduced dose of the 5-HT-1A agonist 8-OH-DPAT necessary to inhibit DRN 5-HT firing activity by 50%. Finally, hippocampal 5-HT levels were lower in TKO than in WT mice. Overall, Syns deletion in mice leads to a reduction in DRN 5-HT firing activity and hippocampal 5-HT levels along with behavioral alterations reminiscent of human neuropsychiatric conditions associated with Syn dysfunction.
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Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Encéfalo
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Serotonina
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Sinapsinas
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Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália