Aims: Bisphenol A (BPA) is an endocrine-disrupting chemical inducing several damages such as neurotoxicity, immunotoxicity, and metabolic disorders. Obesity is the main risk factor for the increased occurrence of metabolic alterations as well as mood disorders. Here, we investigated in obese mice the effects of BPA on anxiety-like behavior, associated with neuroinflammation and immune activation. Main methods: Male C57Bl/6J mice were divided into 4 groups: control group (STD) receiving chow diet and BPA vehicle; STD group treated with BPA (50 μg/kg/die); high-fat diet (HFD) group receiving BPA vehicle; HFD group treated with BPA. BPA treatment started 12 weeks after HFD feeding and lasted 3 weeks. Key findings: The open field and elevated plus-maze tests showed in HFD + BPA group the worsening of HFD-induced anxiety-like behavior. The anxiogenic effects of BPA also emerged from hyperactivation of the hypothalamus-pituitary-adrenal gland axis, determined by the increased transcription of Crh and its receptor in the prefrontal cortex (PFC). Furthermore, BPA activated NLRP3 inflammasome and exacerbated the neuroinflammation induced by HFD, increasing IL-1β, TNF-α and monocyte chemoattractant protein (MCP)-1 in PFC. Furthermore, it induced inflammation and monocyte recruitment in hypothalamus and amygdala. Contextually, BPA significantly amplified the immune activation caused by lipid overload as evidenced by the increased expression of TLR-4 and MCP-1 in the PFC and triggered mastocytosis in the hypothalamus rather than STD mice. Significance: All these data show that sub-chronic BPA exposure represents an additional risk factor for mood disorders strictly related to obesity, enhancing neuroinflammation and immune activation triggered by HFD feeding.

Bisphenol A exacerbates anxiety-like behavior and neuroinflammation in prefrontal cortex of adult obese mice / Lama, A; Del Piano, F; Annunziata, C; Comella, F; Opallo, N; Melini, S; Grumetto, L; Pirozzi, C; Mattace Raso, G; Meli, R; Ferrante, M C. - In: LIFE SCIENCES. - ISSN 1879-0631. - 313:(2023), p. 121301. [10.1016/j.lfs.2022.121301]

Bisphenol A exacerbates anxiety-like behavior and neuroinflammation in prefrontal cortex of adult obese mice

Lama, A;Comella, F;Melini, S;Grumetto, L;Pirozzi, C;Mattace Raso, G;Meli, R;Ferrante, M C
2023

Abstract

Aims: Bisphenol A (BPA) is an endocrine-disrupting chemical inducing several damages such as neurotoxicity, immunotoxicity, and metabolic disorders. Obesity is the main risk factor for the increased occurrence of metabolic alterations as well as mood disorders. Here, we investigated in obese mice the effects of BPA on anxiety-like behavior, associated with neuroinflammation and immune activation. Main methods: Male C57Bl/6J mice were divided into 4 groups: control group (STD) receiving chow diet and BPA vehicle; STD group treated with BPA (50 μg/kg/die); high-fat diet (HFD) group receiving BPA vehicle; HFD group treated with BPA. BPA treatment started 12 weeks after HFD feeding and lasted 3 weeks. Key findings: The open field and elevated plus-maze tests showed in HFD + BPA group the worsening of HFD-induced anxiety-like behavior. The anxiogenic effects of BPA also emerged from hyperactivation of the hypothalamus-pituitary-adrenal gland axis, determined by the increased transcription of Crh and its receptor in the prefrontal cortex (PFC). Furthermore, BPA activated NLRP3 inflammasome and exacerbated the neuroinflammation induced by HFD, increasing IL-1β, TNF-α and monocyte chemoattractant protein (MCP)-1 in PFC. Furthermore, it induced inflammation and monocyte recruitment in hypothalamus and amygdala. Contextually, BPA significantly amplified the immune activation caused by lipid overload as evidenced by the increased expression of TLR-4 and MCP-1 in the PFC and triggered mastocytosis in the hypothalamus rather than STD mice. Significance: All these data show that sub-chronic BPA exposure represents an additional risk factor for mood disorders strictly related to obesity, enhancing neuroinflammation and immune activation triggered by HFD feeding.
2023
Bisphenol A exacerbates anxiety-like behavior and neuroinflammation in prefrontal cortex of adult obese mice / Lama, A; Del Piano, F; Annunziata, C; Comella, F; Opallo, N; Melini, S; Grumetto, L; Pirozzi, C; Mattace Raso, G; Meli, R; Ferrante, M C. - In: LIFE SCIENCES. - ISSN 1879-0631. - 313:(2023), p. 121301. [10.1016/j.lfs.2022.121301]
File in questo prodotto:
File Dimensione Formato  
Meli et al.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Accesso privato/ristretto
Dimensione 3.68 MB
Formato Adobe PDF
3.68 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/919360
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 9
social impact