The oxytocin receptor is essential for the protective effect of pair housing on post-stroke depression in mice.

The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1ß, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.

Disorders in the gut and liver are involved in depression contagion between isosexual post-stroke depression mice and the healthy cohabitors.

Despite the accumulated evidence that pair housing could attenuate post-stroke depression (PSD), but less attention has been paid to the healthy cohabitors, and the underlying mechanisms remain unclear. This study aimed to determine whether there is depressive contagion between PSD mice and their healthy cohabitors. PSD was induced by middle cerebral artery occlusion (MCAO) plus restraint stress for four weeks. Three days after MCAO, the mice were restrained two hours per day and isosexually pair-housed for four weeks. The results showed that, compared with the partners pair housed with normal control mice (Ctrl group), the partners pair housed with PSD mice (CH group) displayed depressive-like behaviors, including decreased sucrose preference rate, significantly shorter duration in the center arena and reduced total distance in the open-field test, and extended immobile time in forced swimming test and tail-suspension test without sex differences. Regarding the change in the body weight, only the males showed a significant reduction on days 17 and 24 after treatment. Furthermore, the CH group showed significantly increased corticosterone and decreased oxytocin (OXT) levels in serum, while the mRNA levels of OXT, vasopressin and oxytocin receptor were remarkably upregulated in the hypothalamus of the CH group. However, there was no significant change in the vasopressin receptor V1a. Interestingly, compared with the Ctrl group, there was a significant decrease in butyrate in serum of the CH group. Consistently, they had mild liver dysfunction with increased alanine transaminase, extended hepatic sinus surrounded by enhanced SLC22A9, and significantly increased Iba1-positive macrophages. Moreover, the expression of tight junction protein (Occludin and ZO-1) obviously decreased in the colon with increasing Iba1-positive cells. These results suggest that isosexual pair-housing with PSD mice causes the healthy partners to develop depressive-like behaviors with disturbances in the gut and liver.