Elevated Thyroid Peroxidase Antibody Increases Risk of Post-partum Depression by Decreasing Prefrontal Cortex BDNF and 5-HT Levels in Mice

Abstract

Post-partum depression (PPD) is a common mental disease in the perinatal period that profoundly affects mothers and their offspring. Some clinical studies have found that PPD is related to thyroid peroxidase antibodies (TPOAbs); however, the mechanism underlying this relationship is unclear. Female C57BL/6 mice immunized with adenovirus encoding the cDNA of the full-length mTPO (mTPO-Ad) were used to establish the isolated TPOAb-positive mouse model in the present study. Maternal depressive-like behaviors were assessed using the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST) post-partum. The serum TPOAb titer was measured by enzyme-linked immunosorbent assay (ELISA) before pregnancy and post-partum. Furthermore, in the prefrontal cortex, the mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF) were measured, serotonin (5-HT) levels were measured by ultra-high-performance liquid chromatography–tandem mass-spectrometry (UHPLC–MS/MS), and total thyroxine (TT4) levels were determined by ELISA. Compared with the controls, the mice immunized with mTPO-Ad displayed depressive behaviors, with a significantly lower sucrose preference (SP) at the 12-h time point and a longer immobility time in the FST and TST, which were accompanied by a lower expression of BDNF and 5-HT but no change in the TT4 concentration in the prefrontal cortex. Together, these findings suggest that elevated TPOAb may increase the risk of subsequent PPD and decrease the concentration of BDNF and 5-HT in the prefrontal cortex.

Functional Status of Hypothalamic–Pituitary–Thyroid and Hypothalamic–Pituitary–Adrenal Axes in Hospitalized Schizophrenics in Shanghai

“…Cohen's d values of TSH (0.488), TT3 (0.503), FT3 (0.587), and ACTH (0.588) showed relatively clear differences when comparing between genders in the schizophrenia group in Table 5. Principles of the autoimmune system indicate immune changes for females after puberty and in the postpartum period by increasing 5-HT (59). The elevated ACTH and T3 (high functioning) may play important roles in the acute illness of male hospitalized schizophrenics with an intense stress response (1).…”

Subclinical Hypothyroidism and Depression: A Systematic Review and Meta-Analysis

“…Thus, in elderly populations, depression is more likely to occur in participants with SCH. This phenomenon may depend on the higher reactivity of 5-HT system to the decreased T4 level in elder people compared with young individuals (34).…”

Neuroprotection of reduced thyroid hormone with increased estrogen and progestogen in postpartum depression

“…Galanin (GAL), as an estrogen-inducible neuropeptide has been linked to depression, with GAL receptor1-siRNA injection reported to reverse the down-regulation of CREB-BDNF and 5-HT levels in the prefrontal cortex of PPD rats [40]. Similarly, enhanced thyroid peroxidase antibody elevates risk of PPD by diminishing BDNF and 5-HT levels in the prefrontal cortex of mice [41]. The deletion of CREB-regulated transcription coactivator 1 (CRTC1) has the capacity to induce impulsive aggressiveness, behavioral despair, psychomotor retardation, increased emotional response to stressful events, anhedonia, and depression-related behaviors [42].…”