Prenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring

Abstract

Objective Central renin–angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined. Results Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT1R and AT2R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT1aR and AT2R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT1R protein and AT1aR mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT2R mRNA and protein were increased only in males. Prenatal dehydration resulted in a significant increase in intracerebroventricular angiotensin II-induced water intake in male, but not female, offspring. Conclusion The results provided new information that antenatal water deprivation induces a reprogramming of brain RAS and Ang II receptor expression patterns and alters the central Ang II-mediated dipsogenic response in offspring in a sex-dependent manner.

Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

“…It might be due to unpalatability of dams to water containing NaAsO 2 . Although we did not observe the obvious signs of maternal or embryonic toxicity such as maternal weight (Figure S1 ) and the number of pups (Figure S2 ) between the two groups of this study, several studies reported the possibility that maternal dehydration due to reduced water intake during pregnancy was associated with long-term physiologic effects on offspring such as development of brain function and plasma composition (Desai et al, 2005 ; Ross et al, 2005 ; Zhang et al, 2011 ). Therefore, we had to assume that behavioral inflexibility observed in mice prenatally exposed NaAsO 2 could be induced by the combinatorial effect of the toxicity of prenatal NaAsO 2 exposure and maternal dehydration.…”

Availability of a rich source of sodium during the perinatal period programs the fluid balance restoration pattern in adult offspring

“…Further studies are necessary to discriminate the precise stage responsible for the changes observed later in life. Previous studies [10][11][12][13]16,21,22,39] have shown that early challenges to osmoregulatory mechanisms involving electrolyte and/or endocrine environmental changes, lead to persistent changes in need-free and stimulated fluid intake and, while most of the work has shown perinatal osmotic alterations, they have contradictory results with regard to how they affect adult offspring fluid intake, and specifically, whether the perinatal manipulation increases or decreases water or sodium ingestion of the adult offspring. Whatever the final PM effect, sometimes the physiological result in terms of body sodium status may be similar.…”

“…angiotensin converting enzyme (ACE) inhibitors, induce an imprinting on osmoregulatory mechanisms, altering their endocrine and behavioral regulatory responses [10][11][12][13][14][15][16]. Perinatal experiences of the stimuli of sodium overload (water deprivation, dietary sodium overload) or sodium depletion (diuretics administration, repeated vomiting during the first trimester of pregnancy, etc.)…”

A Role for the Transcription Factor Nk2 Homeobox 1 in Schizophrenia: Convergent Evidence from Animal and Human Studies

“…Some of these candidates were identified during the pre-GWAS period, with others based on GWAS studies. NKX2-1 is known to interact with a number of these genes (Thome et al, 1996 ; Perrone et al, 1999 ; Stober et al, 1999 ; Marin et al, 2000 ; Naltner et al, 2000 ; Ojeda et al, 2000 ; Stoykova et al, 2000 ; Kim et al, 2002 ; Leonard et al, 2002 ; Yi et al, 2002 ; Chojnacki and Weiss, 2004 ; Cui et al, 2005 ; Ide et al, 2005 ; Reynolds and Hoidal, 2005 ; Aghajani et al, 2006 ; Sanjuan et al, 2006 ; Takahashi et al, 2006 ; Benzel et al, 2007 ; Hashimoto et al, 2007 ; Son et al, 2007 ; Takao et al, 2007 ; Kahler et al, 2008 ; Zhou et al, 2008 ; Leon et al, 2009 ; Carney et al, 2010 ; Waddington et al, 2010 ; Goulburn et al, 2011 ; Zhang et al, 2011 ; Crisafulli et al, 2012 ; Matagne et al, 2012 ; Quednow et al, 2012 ; Li T. et al, 2013 ; Trotman et al, 2013 ; Zscheppang et al, 2013 ; Luo et al, 2014 ) (Table 1 ).…”