Gestational Hypothyroxinemia Imprints a Switch in the Capacity of Astrocytes and Microglial Cells of the Offspring to React in Inflammation

Abstract

Hypothyroxinemia (Hpx) is a highly frequent condition characterized by low thyroxine (T) and normal 3,3',5'-triiodothyronine (T) and thyroid stimulating hormone (TSH) levels in the blood. Gestational Hpx is closely related to cognitive impairment in the human offspring. In animal models gestational Hpx causes impairment at glutamatergic synapsis, spatial learning, and the susceptibility to suffer strong autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying these phenotypes are unknown. On the other hand, it has been shown that astrocytes and microglia affect the outcome of EAE. In fact, the activation of astrocytes and microglia in the central nervous system (CNS) contributes to EAE progression. Thus, in this work, the reactivity of astrocytes and microglia from rats gestated in Hpx was evaluated aiming to understand whether these cells are targets of gestational Hpx. Interestingly, microglia derived from the offspring gestated in Hpx were less reactive compared to microglia derived from offspring gestated in euthyroidism. Instead, astrocytes derived from the offspring gestated in Hpx were significantly more reactive than the astrocytes from the offspring gestated in euthyroidism. This work contributes with novel information regarding the effects of gestational Hpx over astrocytes and microglia in the offspring. It suggests that astrocyte could react strongly to an inflammatory insult inducing neuronal death in the CNS.

Iodine as Essential Nutrient during the First 1000 Days of Life

“…Maternal hypothyroxinemia during the first half of gestation has been associated with permanent and irreversible neurological alterations in the embryo and the foetus [ 44 ]. Experimental animal studies have contributed to a better characterization of cerebral areas affected by inadequate availability of fT4 ( Table 1 ) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes

“…Gestational HTX was induced in pregnant mice according to previous reports ( 52 – 55 ). Six- to eight-week-old C57BL/6 mice were mated in a proportion of 2 females and 1 male.…”

Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells

“…An interplay between thyroid hormone action and peripheral immune cells has been established with evidence of actions in both the innate and adaptive immune responses (Montesinos and Pellizas, 2019). Earlier work reported that microglia express the a1 and b1 isoforms of nuclear thyroid hormone receptors (Lima et al, 2001) and, under conditions of developmental hypothyroxinemia, show a decrease in cellprocess complexity Lima et al, 2001) and diminished response to a LPS challenge (Opazo et al, 2018). Thus, if exposure results in a direct effect upon microglia or if the effect is secondary to a shift in thyroid hormone or a change in BBB transporters, there remains an effect upon these critical cells of the brain even if only localized to those microglia in contact with the vascular wall.…”