The editorial office of The Anatomical Record is pleased to launch AR Highlights as new content. The purpose of AR Highlights is to draw attention to papers that are published in recent issues of the Journal. AR Highlights are written by the Journal's Science Writer, Ellen Jensen
Genetic Models of Serotonin (5-HT) Depletion: What Do They Tell Us About the Developmental Role of 5-HT? by Sara Trowbridge, Nicolas Narboux-Nême, and Patricia Gaspar. Anat Rec 294:1615–1623
Serotonin (5-HT) has many important functions during development. Therefore, it is speculated that there is a link between 5-HT and dysfunction and neurological developmental disorders, such as autism. The mouse has proven to be a useful genetic model for the developmental role of 5-HT. Early genetic models showed that increasing amounts of 5-HT during development modulate neural circuits and affect subsequent adult behavior. However, there is conflicting evidence in recent genetic models with decreased 5-HT levels in the brain, where the brain develops normally. In this article, the authors review the existing literature on genetic hyposerotonergic models. They discuss the main strategies that have been used to obtain mice with low 5-HT levels and summarize the neurological and behavioral changes that have been observed in these models. While these models appear to have normal brain development as mentioned above, there are problems with somatic growth and physiological functions. Abnormal adult behavior is also observed. The varied sources of 5-HT during development comprise a complex system with many different serotonin receptor subtypes in which small changes in the method of 5-HT depletion or in the timing of the depletion can result in very different phenotypes. These mice models could provide important insights into the mechanisms underlying various human mental disorders, which appear in adults but are believed to originate from developmental abnormalities. The authors also discuss the need to better characterize the behavioral phenotype of hyposerotonergic mice as well as determine how the effects of developmental depletion of 5-HT relate to effects of functional 5-HT deficiency during adult life.
Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABAA Receptor Beta 3 in Adults with Autism by S. Hossein Fatemi, Timothy D. Folsom, Rachel E. Kneeland and Stephanie B. Liesch. Anat Rec 294:1635–1645
Autism is a neurodevelopmental disorder that is characterized by impaired social interaction and communication and repetitive behavior. It is a debilitating disease with no known cure. Recent findings in autism have investigated abnormality of GABAergic neurotransmission. Since previous reports have shown the presence of autistic behavior in patients with Fragile X syndrome, and that lower levels of Fragile X mental retardation protein (FMRP) expression may cause autistic behavior, the authors decided to investigate whether FMRP levels could be lower in children and adults with autism and aimed to relate FMRP levels to GABAA receptor underexpression. Indeed, the authors found reduced FMRP levels and GABAA receptor beta 3 protein in the vermis of adults with autism. This reduction in FMRP is intriguing since none of the subjects used in their study were diagnosed with Fragile X syndrome. Another important, novel finding is that metabotropic glutamate receptor 5 (involved in a number of important functions both during brain development and in adult life) protein levels were increased in the vermis of children with autism. The results of this study provide further insight into the mechanisms of autism and provide several promising avenues of possible future treatments for autism.
Fetal Lung Epithelial Ion Channels Relocate in the Cell Membrane During Late Gestation by Lamonta L. Beard, Tianbo Li, Yang Hu, and Hans G. Folkesson. Anat Rec 294:1461–1471
At the end of gestation, the direction of ion and fluid flow across the lung rapidly changes from secretion to absorption. In the lungs, Na generates the driving force for fluid absorption. Na transport by epithelial Na channels (ENaCs) requires Cl transport (i.e., the cystic fibrosis transmembrane regulator [CFTR]). The authors investigated the cellular location of Na and Cl channels during fetal lung development and after interleukin (IL)-1β (stimulates lung maturation) pretreatment in guinea pigs. Their results indicate that IL-1β may activate ENaC, which in turn leads to induced distal lung fluid absorption in fetal lungs. This suggests that the appearance of ENaC in alveolar epithelial type I cells may be responsible, in part, for the conversion of the alveolar epithelium from distal lung fluid secretion to fluid absorption. The presence of ENaC at the cell membrane is essential for removal of fetal lung fluid at birth. Additionally, the authors found that increased gestational age was associated with a relocation of ENaC subunits and CFTR Cl channels, resulting in a more mature lung. This concept provides a novel molecular model for the rapid transition from distal lung fluid secretion in fetal lungs to absorption in near-term and newborn lungs. Ultimately, the authors' findings could lead to a better understanding of the molecular mechanisms at the membrane level responsible for the very rapid transition from a fluid-secreting lung to a fluid absorbing lung at birth, and assist in development of new drugs for treatment of preterm babies suffering from respiratory distress syndrome.