Environmental enrichment by targeting hippocampal claudins attenuates depressive-like behaviours in maternally separated male mice.

Abstract

OBJECTIVES: Maternal separation (MS) is a well-established risk factor for psychological disorders like depression. Alterations in the blood-brain barrier (BBB) and its tight junction proteins, such as claudins (CLDNs), may contribute to the pathophysiology of depression. Environmental enrichment (EE) has shown antidepressant-like effects, though its exact underlying mechanisms remain incompletely understood. This study aimed to assess the effect of EE on depressive-like behaviours induced by MS in male mice, centring on hippocampal CLDNs. METHODS: Thirty-two male NMRI mice were randomly divided into control (C), MS, MS+EE, and C + EE groups. The MS paradigm was conducted from postnatal day (PND) 2 to 14. EE was implemented between PND 45 and 60. Behavioural tests, including the open field (OFT), forced swimming (FST), and splash tests, were performed. qRT-PCR was performed to evaluate the hippocampal expression of,, and. RESULTS: MS induced depression-like behaviours, as an increase in immobility time in the FST and a decrease in grooming activity time in the splash test. MS increased the expression of,, andin the hippocampus. EE significantly reduced depressive-like behaviours and downregulatedand-gene expression, whileoverexpressed. CONCLUSIONS: EE exerts antidepressant-like effects, potentially through modulation of BBB-associated CLDNs.