Rett Syndrome and Plasma Leptin Levels

Blardi, Patrizia; Lalla, A. De; D'Ambrogio, Tatiana; Zappella, Michele; Cevenini, Gabriele; Ceccatelli, L.; Auteri, Alberto; Hayek, Joussef

doi:10.1016/j.jpeds.2006.10.061

Cited by 19 publications

(19 citation statements)

References 13 publications

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“…It is known that in obese children and adults, leptin concentrations are increased. We previously found that in patients with Rett syndrome leptin concentrations were increased, but not associated with obesity 8 . In this study, we confirmed that in Rett patients leptin levels rise in the long period, without being associated to obesity.…”

Section: Discussionsupporting

confidence: 88%

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Long‐term plasma levels of leptin and adiponectin in Rett syndrome

Blardi

Lalla

D'Ambrogio

et al. 2009

Clinical Endocrinology

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Section: Discussionsupporting

confidence: 88%

“…In a previous investigation, we found that in patients affected by Rett syndrome plasma levels of leptin were increased, but not associated to obesity; we hypothesized that leptin might be related to factors other than adiposity 8 …”

Section: Introductionmentioning

confidence: 86%

Long‐term plasma levels of leptin and adiponectin in Rett syndrome

Blardi

Lalla

D'Ambrogio

et al. 2009

Clinical Endocrinology

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“…Likely mediators of this effect are hypothalamic Sim1-expressing neurones, which when selectively depleted of Mecp2 also caused a hyperphagic phenotype. A possible explanation for this phenotype is either the deregulation of the melanocortin pathway [19] or a rise in leptin levels, which has been observed in Rett patients [47] and is similarly found in obese children and adults [48]. The absence of Mecp2 in the hypothalamus could therefore explain the hyperphagic and obesity-like phenotype of our female Mecp2 Stop mice, but requires further confirmatory studies.…”

Section: Discussionmentioning

confidence: 59%

Long-term home cage activity scans reveal lowered exploratory behaviour in symptomatic female Rett mice

Robinson

Plano

Cobb

et al. 2013

Behavioural Brain Research

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HighlightsMecp2Stop mutant female mice develop Rett-like symptoms late in life (>6 months).Symptoms include anomalies in motor, activity and anxiety profiles and were assessed in various behavioural tasks.Deficits occurred in ambulatory activity during novelty exploration and habituation to a novel environment.Circadian rhythms and anxiety were not affected, but food intake was higher and global activity lower in mutant mice.

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“…Leptin is of interest to Rett syndrome researchers, because of the associated growth failure and low BMI. Similar to ASD, leptin is elevated in patients with Rett syndrome compared to controls of similar BMI (Blardi et al, 2009; Blardi et al, 2007). Leptin levels are also significantly increased in patients with Rett syndrome over the course of a two-year study (Blardi et al, 2009).…”

Section: Leptin’s Role In Psychopathologymentioning

confidence: 93%

The impact of leptin on perinatal development and psychopathology

Valleau

Sullivan

2014

Journal of Chemical Neuroanatomy

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Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as antipsychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including Autism Spectrum Disorders and Rhett disorder. Further studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations.

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Rett Syndrome and Plasma Leptin Levels

Cited by 19 publications

References 13 publications

Long‐term plasma levels of leptin and adiponectin in Rett syndrome

Long‐term plasma levels of leptin and adiponectin in Rett syndrome

Long-term home cage activity scans reveal lowered exploratory behaviour in symptomatic female Rett mice

The impact of leptin on perinatal development and psychopathology

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