Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression.
J Affect Disord
; 359: 241-252, 2024 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-38768820
ABSTRACT
BACKGROUND:
Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated.METHODS:
We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice.RESULTS:
We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo.LIMITATIONS:
L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types.CONCLUSION:
Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Atrofia
/
Prostaglandina D2
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Transducción de Señal
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Astrocitos
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Depresión Posparto
/
Modelos Animales de Enfermedad
Límite:
Animals
Idioma:
En
Revista:
J Affect Disord
Año:
2024
Tipo del documento:
Article
País de afiliación:
China