Loss of choroid plexus-derived insulin-like growth factor 2 (IGF2) leads to hyposmia, while retaining post-partum mood resilience in mice.

During the post-partum period, new mothers are vulnerable to mood disorders. In adults, impairments in neurogenesis commonly associate with anxiety and depressive behaviors. Insulin-like growth factor 2 (IGF2) is expressed in the choroid plexus (CP) within the subventricular zone (SVZ) neurogenic niche, and global loss of IGF2 leads to increased anxiety. Previously, we have shown that Igf2 expression in CP tissue increases 6-fold during lactation but returns to baseline on suppression of prolactin present in lactation, suggesting it is induced by high levels of prolactin. To gain more insight into the role of prolactin-induced Igf2 expression in the CP, we have measured IGF2 levels in cerebrospinal fluid across reproductive states and developed mice in which Igf2 is conditionally removed from the CP. Using CP-derived IGF2 knockout mouse models, we have measured Prlr expression in CP tissue, SVZ mitogenesis, olfaction, and anxiety-like behavior using an elevated plus maze (EPM) and light/dark transition test (LDTT). Interestingly, we observed a reduction in Prlr expression in CP tissue in one of our Igf2 knockout mouse models, suggesting Igf2 may also act upstream to regulate Prlr expression in CP tissue. No changes were detected in SVZ proliferation rates between Igf2 knockout and controls. Using a buried food test (BFT), however, we show mice with conditional loss of Igf2 in the CP take longer to find a buried fruit loop as compared to controls, indicating olfaction deficits. Overall anxiety levels, however, were comparable between knockout and controls in the EPM and LDTT. Together, our findings reveal loss of CP-derived IGF2 leads to hyposmia in the absence of detectable changes to SVZ mitogenesis. We propose that CP-derived IGF2 may be acting directly in the olfactory bulb to elicit changes to improve olfaction, which may become particularly important during the post-partum period to facilitate mother-pup interactions.