Postnatal Effects of Retinoic Acid on Cerebellar Development

Yamamoto, Miyuki; Ullman, David; Dräger, Ursula C.; McCaffery, Peter

doi:10.1016/s0892-0362(98)00048-8

Cited by 27 publications

(18 citation statements)

References 20 publications

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“…In newborn rats (2, 13, 15) and mice (11), corticosteroid hormones markedly impair alveolus formation; this is prevented (14) and reversed (11) by the intraperitoneal administration of ATRA. However, there are potentially harmful effects on nonpulmonary developing organs of systemically administered ATRA in humans (17,21). Therefore, the addition of ATRA to SAM already being instilled into the endotracheal tube as treatment in prematurely born babies, in light of the seeming absence of a systemic effect of ATRA in mice, might make a clinical trial of ATRA feasible in very prematurely born babies.…”

Section: Resultsmentioning

confidence: 99%

“…alveolus formation by corticosteroids in rats (15) and therefore might do the same in prematurely born babies; however, retinoids carry their own risks, especially on the developing brain (17,21). These considerations of potential therapy and the need to easily alter specific gene expression in the lung for experimental purposes led us to test the hypothesis that reagents could be effectively delivered to the alveolus in a technically simple, noninvasive manner, using SAM as the delivery vehicle.…”

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confidence: 99%

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Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice

Massaro

Clerch

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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-A technically easy, noninvasive means of delivering molecules to alveoli, which act selectively or specifically in the lung, would be experimentally and therapeutically useful. As proof of principle, we took advantage of the spreading ability of pulmonary surface active material (InfaSurf), mixed it with elastase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) small inhibitory RNA (siRNA), or all-trans retinoic acid (ATRA), and instilled microliter amounts of the mixture into the nose of lightly anesthetized mice. One instillation of elastase caused diffuse alveolar destruction (emphysema) demonstrating widespread alveolar delivery. A single nasal instillation of GAPDH siRNA, compared with scrambled GAPDH siRNA, lowered GAPDH protein in lung, heart, and kidney by ϳ50 -70% 1 and 7 days later. To test the possibility of lung-specific delivery of a potentially therapeutic drug, we administered ATRA and monitored its effect on expression of cellular retinol binding protein (CRBP)-1 mRNA, whose translation product is a key molecule in retinoid metabolism. Given intranasally, ATRA elevated CRBP-1 mRNA 4.3-fold in a lung-specific manner. The same dose and dose schedule of ATRA given intraperitoneally increased CRBP-1 mRNA only ϳ1.8-fold in lung; intraperitoneally administered ATRA elevated expression of CRBP-1 mRNA 1.7-fold or more in brain cortex, cerebellum, and testes, thereby increasing the risk of untoward effects. This simple noninvasive technique allows regulation of specific proteins in the lung and lung-specific delivery of reagents of experimental and potentially therapeutic importance. bronchopulmonary dysplasia; emphysema; brain; kidney; retinoic acid PULMONARY SURFACTANT (surface active material or SAM), a lipoprotein with great ability to spread, lines the alveoli (3, 4, 8), prevents alveolar collapse at low lung volume, and diminishes alveolar opening pressure (1, 9). Very prematurely born babies may develop bronchopulmonary dysplasia (BPD), which is characterized, in part, by an inadequate amount of SAM (1), pulmonary inflammation, excess matrix metalloproteinase activity, and arrested alveolar development (23). Exogenous SAM, delivered into the trachea, is commonly used to augment endogenous surfactant in very prematurely born babies (23). Anti-inflammatory corticosteroids given systemically are also used in the treatment of BPD (23), but they markedly impair alveolus formation in newborn rats (2, 16) and mice (11) and, hence, might do the same in humans. All-trans retinoic acid (ATRA) prevents the impairment of alveolus formation by corticosteroids in rats (15) and therefore might do the same in prematurely born babies; however, retinoids carry their own risks, especially on the developing brain (17, 21). These considerations of potential therapy and the need to easily alter specific gene expression in the lung for experimental purposes led us to test the hypothesis that reagents could be effectively delivered to the alveolus in a technically simple, noninvasive manner, using SAM as the delivery ve...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice

Massaro

Clerch

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Also on Chr 1 is the retinoid ϫ receptor gene (Rxrg; 88.1 cM). Retinoic acid receptors are expressed in the cerebellum of the rat, and granule cell loss results from teratogenic effects of the ligand (Yamamoto et al, 1999).…”

Section: Candidate Genesmentioning

confidence: 99%

Genetic Control of the Mouse Cerebellum: Identification of Quantitative Trait Loci Modulating Size and Architecture

Airey

Williams

2001

J. Neurosci.

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To discover genes influencing cerebellum development, we conducted a complex trait analysis of variation in the size of the adult mouse cerebellum. We analyzed two sets of recombinant inbred BXD strains and an F2 intercross of the common inbred strains, C57BL/6J and DBA/2J. We measured cerebellar size as the weight or volume of fixed or histologically processed tissue. Among BXD recombinant inbred strains, the cerebellum averages 52 mg (12.4% of the brain) and ranges 18 mg in size. In F2 mice, the cerebellum averages 62 mg (12.9% of the brain) and ranges ϳ20 mg in size. Five quantitative trait loci (QTLs) that significantly control variation in cerebellar size were mapped to chromosomes 1 (Cbs1a), 8 (Cbs8a), 14 (Cbs14a), and 19 (Cbs19a, Cbs19b). In combination, these QTLs can shift cerebellar size an appreciable 35% of the observed range. To assess regional genetic control of the cerebellum, we also measured the volume of the cell-rich, internal granule layer (IGL) in a set of BXD strains. The IGL ranges from 34 to 43% of total cerebellar volume. The QTL Cbs8a is significantly linked to variation in IGL volume and is suggestively linked to variation in the number of cerebellar folia. The QTLs we have discovered are among the first loci shown to modulate the size and architecture of the adult mouse cerebellum.

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“…Previous studies have demonstrated that retinoic acid (RA) is necessary for the normal development of the central nervous system (CNS), and abnormal development occurs following embryonic or postnatal exposure to high levels of RA (1)(2)(3)(4)(5). On the one hand, RA deficiency causes CNS developmental defects during embryogenesis and CNS diseases in adults (1,6,7).…”

Section: Introductionmentioning

confidence: 99%

“…On the one hand, RA deficiency causes CNS developmental defects during embryogenesis and CNS diseases in adults (1,6,7). On the other hand, excess RA during embryo and fetal development also causes morphological and behavioral problems such as neural tube defects (1)(2)(3)(4)(5). Therefore, appropriate RA signaling is very important in maintaining normal CNS development and function.…”

Section: Introductionmentioning

confidence: 99%

p38 Mitogen‐activated protein kinase‐dependent regulation of SRC‐3 and involvement in retinoic acid receptor α signaling in embryonic cortical neurons

Chai

Yang

et al. 2009

IUBMB Life

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Appropriate retinoic acid (RA) signaling is essential in the development of the central nervous system (CNS). Previous studies have shown that RA activates p38 mitogen‐activated protein kinase (MAPK) and steroid receptor coactivator (SRC)‐3 in tumor cells in vitro. It is unknown whether the activation of p38 MAPK and SRC‐3 is involved in RA‐mediated CNS development. The current study investigated a possible role for p38 MAPK in the regulation of (SRC)‐3 phosphorylation/degradation and in retinoic acid receptor (RAR)α signaling in mouse fetal cortical neurons treated with all‐trans retinoic acid (ATRA). Results showed that ATRA treatment rapidly activated p38 MAPK, which in turn resulted in phosphorylation with subsequent degradation of SRC‐3. Inhibition of p38 MAPK by SB203580 blocked the phosphorylation and degradation of SRC‐3. The binding of RARα to retinoic acid responsive element (RARE) was rapidly increased in neurons following ATRA treatment. Inhibition of p38 MAPK significantly enhanced the RARα‐RARE binding activity, but had no effects on ATRA‐induced decrease of RARα. Treatment of the fetal cortical neurons with ATRA significantly increased the expression of HOXd3, a retinoid‐target gene. The increase of HOXd3 expression was augmented when p38 MAPK activity was inhibited by a specific inhibitor, SB203580. Results suggest that ATRA activates the p38 MAPK signal pathway with resultant degradation of SRC‐3, and that p38 MAPK is involved in the regulation of RARα‐mediated signaling in developing neurons. © 2009 IUBMB IUBMB Life, 61(6): 670–678, 2009

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Postnatal Effects of Retinoic Acid on Cerebellar Development

Cited by 27 publications

References 20 publications

Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice

Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice

Genetic Control of the Mouse Cerebellum: Identification of Quantitative Trait Loci Modulating Size and Architecture

p38 Mitogen‐activated protein kinase‐dependent regulation of SRC‐3 and involvement in retinoic acid receptor α signaling in embryonic cortical neurons

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