On dendrites in Down syndrome and DS murine models: a spiny way to learn

Since the discovery in the 1970s that dendritic abnormalities in cortical pyramidal neurons are the most consistent pathologic correlate of mental retardation, research has focused on how dendritic alterations are related to reduced intellectual ability. Due in part to obvious ethical problems and in part to the lack of fruitful methods to study neuronal circuitry in the human cortex, there is little data about the microanatomical contribution to mental retardation. The recent identification of the genetic bases of some mental retardation associated alterations, coupled with the technology to create transgenic animal models and the introduction of powerful sophisticated tools in the field of microanatomy, has led to a growth in the studies of the alterations of pyramidal cell morphology in these disorders. Studies of individuals with Down syndrome, the most frequent genetic disorder leading to mental retardation, allow the analysis of the relationships between cognition, genotype and brain microanatomy. In Down syndrome the crucial question is to define the mechanisms by which an excess of normal gene products, in interaction with the environment, directs and constrains neural maturation, and how this abnormal development translates into cognition and behaviour. In the present article we discuss mainly Down syndrome-associated dendritic abnormalities and plasticity and the role of animal models in these studies. We believe that through the further development of such approaches, the study of the microanatomical substrates of mental retardation will contribute significantly to our understanding of the mechanisms underlying human brain disorders associated with mental retardation. (C) 2004 Elsevier Ltd. All rights reserved.

Influence of growth hormone on the craniofacial complex of transgenic mice

Growth hormone (GH) secretion affects bone and cartilage physiology. This study investigated the effect of GH on the size of the craniofacial structures and their angular relationship. Three different models of mice with a genetically altered GH axis were used: GH excess (giant), dwarf GH antagonist (dwarf-Ant), and dwarf GH receptor knockout (dwarf-KO) mice. Each model was compared with the corresponding wild type (Wt). Five craniofacial distances were analysed: craniofacial length, upper face height, mandibular anterior height, mandibular ramus length, and mandibular corpus length. In addition, upper and lower incisor lengths and four angular relationships, nasal bone with cranial base, maxillary plane with cranial base, mandibular plane with cranial base, and the angle of the mandible, were determined. Data were analysed by one-way ANOVA. Craniofacial length, upper face height and mandibular corpus length were significantly increased in the giant mice and significantly reduced in the dwarf mice. Mandibular anterior height and mandibular ramus length were significantly affected in the dwarf-KO mice but not in the giant mice. The length of both the upper and lower incisors was significantly increased and reduced in the giant and dwarf-KO mice, respectively. In addition, the angle of the mandible was significantly increased in the giant mice and significantly reduced in the dwarf mice. It is concluded that GH plays a major role in the growth and development of the craniofacial complex by directly and indirectly modulating the size and the angular relationships of the craniofacial structures, including the incisor teeth.