Ontogeny of hypothalamic-hindbrain feeding control circuits

Rinaman, Linda

doi:10.1002/dev.20146

Cited by 26 publications

(23 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, PVN neuronal projections – in particular, oxytocinergic neurons projecting to the NTS – continue to develop postnatally. Data from mice are not available, but in rats, the development of PVN to hindbrain projections (reviewed in (Rinaman, 2006)) is completed by postnatal day 20. We examined the projections from the PVN to the hindbrain as well as the median eminence (ME) in conventional Sim1 heterozygotes and wild type littermates and saw no qualitative difference.…”

Section: Discussionmentioning

confidence: 99%

PostnatalSim1Deficiency Causes Hyperphagic Obesity and ReducedMc4randOxytocinExpression

Tolson

Gemelli

Gautron³

et al. 2010

J. Neurosci.

127

118

View full text Add to dashboard Cite

Single-minded 1 (SIM1) mutations are one of the few known causes of nonsyndromic monogenic obesity in both humans and mice. Although the role of Sim1 in the formation of the hypothalamus has been described, its postdevelopmental, physiological functions have not been well established. Here we demonstrate that postnatal CNS deficiency of Sim1 is sufficient to cause hyperphagic obesity. We conditionally deleted Sim1 after birth using CaMKII-Cre (␣-calcium/calmodulin-dependent protein kinase II-Cre) lines to recombine a floxed Sim1 allele. Conditional Sim1 heterozygotes phenocopied germ line Sim1 heterozygotes, displaying hyperphagic obesity and increased length. We also generated viable conditional Sim1 homozygotes, demonstrating that adult Sim1 expression is not essential for mouse or neuron survival and revealing a dosage-dependent effect of Sim1 on obesity. Using stereological cell counting, we showed that the phenotype of both germ line heterozygotes and conditional Sim1 homozygotes was not attributable to global hypocellularity of the paraventricular nucleus (PVN) of the hypothalamus. We also used retrograde tract tracing to demonstrate that the PVN of germ line heterozygous mice projects normally to the dorsal vagal complex and the median eminence. Finally, we showed that conditional Sim1 homozygotes and germ line Sim1 heterozygotes exhibit a remarkable decrease in hypothalamic oxytocin (Oxt) and PVN melanocortin 4 receptor (Mc4r) mRNA. These results demonstrate that the role of Sim1 in feeding regulation is not limited to formation of the PVN or its projections and that the hyperphagic obesity in Sim1-deficient mice may be attributable to changes in the leptin-melanocortin-oxytocin pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

PostnatalSim1Deficiency Causes Hyperphagic Obesity and ReducedMc4randOxytocinExpression

Tolson

Gemelli

Gautron³

et al. 2010

J. Neurosci.

127

118

View full text Add to dashboard Cite

show abstract

“…A good candidate is the hindbrain dorsal vagal complex (DVC), to which neural projections descending from hypothalamus connect. The DVC has been implicated in the regulation of neonatal milk intake [49], as well as adult feeding behavior and visceral responses [50].…”

Section: Discussionmentioning

confidence: 99%

Neonatal Maternal Deprivation Response and Developmental Changes in Gene Expression Revealed by Hypothalamic Gene Expression Profiling in Mice

Ding

et al. 2010

PLoS ONE

View full text Add to dashboard Cite

Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.

show abstract

“…The most basic type of control over food intake, meal initiation and termination, develops earliest. Autonomic circuits linking the stomach and feeding circuits in the hypothalamus and brainstem are observed at birth and expand rapidly within the first week of lactation [39,40]. Gastric distension can suppress food intake as early as postnatal day 1 (P1), while postabsorptive nutritional signals from the gut operate after P9-11 [41,42](reviewed in [40]).…”

Section: Introductionmentioning

confidence: 99%

Developmental influences on circuits programming susceptibility to obesity

Zeltser

2015

Frontiers in Neuroendocrinology

View full text Add to dashboard Cite

Suboptimal maternal nutrition exerts lasting impacts on obesity risk in offspring, but the direction of the effect is determined by the timing of exposure. While maternal undernutrition in early pregnancy is associated with increased body mass index, in later pregnancy it can be protective. The importance of the timing of maternal undernutrition is also observed in rodents, however, many of the processes that occur in the last trimester of human gestation are delayed to the postnatal period. Neonatal leptin administration exerts lasting impacts on susceptibility to obesity in rodents. Although leptin can influence the formation of hypothalamic circuits involved in homeostatic control of feeding during the postnatal period, these effects are too late to account for its ability to reverse adverse metabolic programming due to early gestational exposure to maternal undernutrition. This review presents an alternative framework for understanding the effects of neonatal leptin through influences on developing thermoregulatory circuits.

show abstract

Ontogeny of hypothalamic-hindbrain feeding control circuits

Cited by 26 publications

References 77 publications

PostnatalSim1Deficiency Causes Hyperphagic Obesity and ReducedMc4randOxytocinExpression

PostnatalSim1Deficiency Causes Hyperphagic Obesity and ReducedMc4randOxytocinExpression

Neonatal Maternal Deprivation Response and Developmental Changes in Gene Expression Revealed by Hypothalamic Gene Expression Profiling in Mice

Developmental influences on circuits programming susceptibility to obesity

Contact Info

Product

Resources

About