Developmental zinc deficiency impairs cortical astrogliogenesis by disrupting the STAT3 signaling pathway

SUANGSUDA SUPASAI; REGINA C. MARINO; PATRICIA MATHIEU; PATRICIA I. OTEIZA; ANA M. ADAMO; ADDIE HELLMERS

Davis, CA

Congreso; World Congress on "Redox Medicine and Nutrition"; 2016

We previously observed that gestational marginal zinc deficiency (MZD) disruptsthe STAT3 signaling pathway in the developing rat brain and in IMR-32 cells. Weobserved altered STAT3 phosphorylation patterns, low STAT3 nuclear translocation,DNA binding, and transactivating activity. Given that STAT3 is critical for astrogliogenesis, this work investigated the effects of MZD on STAT3 signaling at different stages in brain development and its potential impact on astrogliogenesis. Pregnant rats were fed diets containing 10 (MZD) or 25 mg Zn/g (control) from embryonic day (E) 0 through postnatal day (P) 2, after which all animals were fed the control diet until P56. Gestational MZD impaired cortical STAT3 activation, which coincided with the timing of astrogliogenesis. Low STAT3 phosphorylation in MZD brain was associated with: i) low JAK2 activation; ii) high PTP1B expression and activity; iii) low PTP1B ubiquitination/degradation. MZD also affected STAT3/cytoskeleton interactions and STAT3 acetylation. Consistent with an impaired STAT3 signaling, gestational MZD caused a deregulation of astrogliogenesis. This was evidenced by altered brain cortex patterns of expression of the astrogliogial markers GFAP and S100β. At P56, we observed, by immunohistochemistry, both a lower number of astrocytes in MZD cortex, and a disruption in the migration of astrocyte precursors. Insummary, a low Zn availability during early brain development affects astrogliogenesis as a consequence of a disruption in STAT3 signaling. Thus, developmental MZD could alter brain cell number, type (astrocytes) and distribution, potentially causing long lasting effects on brain homeostasis and function.Supported by NIFA-USDA (CA-D*-XXX-7244-H) and PackerWentz Endowment.