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

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 forastrogliogenesis, this work investigated the effects of MZD on STAT3 signaling atdifferent stages in brain development and its potential impact on astrogliogenesis.Pregnant rats were fed diets containing 10 (MZD) or 25 mg Zn/g (control) fromembryonic day (E) 0 through postnatal day (P) 2, after which all animals were fed thecontrol diet until P56. Gestational MZD impaired cortical STAT3 activation, whichcoincided with the timing of astrogliogenesis. Low STAT3 phosphorylation in MZDbrain was associated with: i) low JAK2 activation; ii) high PTP1B expression andactivity; iii) low PTP1B ubiquitination/degradation. MZD also affectedSTAT3/cytoskeleton interactions and STAT3 acetylation. Consistent with an impairedSTAT3 signaling, gestational MZD caused a deregulation of astrogliogenesis. This wasevidenced by altered brain cortex patterns of expression of the astrogliogial markersGFAP and S100β. At P56, we observed, by immunohistochemistry, both a lower numberof astrocytes in MZD cortex, and a disruption in the migration of astrocyte precursors. Insummary, a low Zn availability during early brain development affects astrogliogenesisas a consequence of a disruption in STAT3 signaling. Thus, developmental MZD couldalter brain cell number, type (astrocytes) and distribution, potentially causing long lastingeffects on brain homeostasis and function.Supported by NIFA-USDA (CA-D*-XXX-7244-H) and PackerWentz Endowment.