A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

Mecp2 truncation in male mice promotes affiliative social behavior.

Mouse models of Rett syndrome, with targeted mutations in the Mecp2 gene, show a high degree of phenotypic consistency with the clinical syndrome. In addition to severe and age-specific regression in motor and cognitive abilities, a variety of studies have demonstrated that Mecp2 mutant mice display impaired social behavior. Conversely, other studies indicate complex enhancements of social behavior in Mecp2 mutant mice. Since social behavior is a complicated accumulation of constructs, we performed a series of classic and refined social behavior tasks and revealed a relatively consistent pattern of enhanced pro-social behavior in hypomorphic Mecp2 (308/Y) mutant mice. Analyses of repetitive motor acts, and cognitive stereotypy did not reveal any profound differences due to genotype. Taken together, these results suggest that the mutations associated with Rett syndrome are not necessarily associated with autism-relevant social impairment in mice. However, this gene may be a valuable candidate for revealing basic mechanisms of affiliative behavior.

Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism.

The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.

Lumbar-pelvic range and coordination during lifting tasks.

Spine motion has been described to have two regions, a neutral zone where lumbar rotation can occur with little resistance and an elastic zone where structures such as ligaments, facet joints and intervertebral disks resist rotation. In vivo, the passive musculature can contribute to further limiting the functional neutral range of lumbar motion. Movement out of this functional neutral range could potentially put greater loads on these structures. In this study, the range of lumbar curvature rotation was examined in twelve healthy, untrained volunteers at four torso inclination angles. The lumbar curvature during straight-leg lifting tasks was then defined as a percentage of this range of possible lumbar curvatures. Subjects were found to remain neutrally oriented during the flexion phase of a lifting task. During the extension phase of the lifting task, however, subjects were found to assume a more kyphotic posture, approaching the edge of the functional range of motion. This was found to be most pronounced for heavy lifting tasks. By allowing the lumbar curvature to go into a highly kyphotic posture, subjects may be taking advantage of stretch-shortening behavior in extensor musculature and associated tendons to reduce the energy required to raise the torso. Such a kyphotic posture during extension, however, may put excessive loading on the elastic structures of the spine and torso musculature increasing the risk of injury.

Rapid maxillary expansion with incisor intrusion: a study of vertical control.

This is a prospective study of 20 consecutively treated patients needing maxillary expansion and incisor intrusion. The patients were treated with a bonded maxillary expansion appliance, intrusion of the incisors with either a one-piece or three-piece base arch and anchorage augmented by the use of vertical-pull chincup therapy. Because rapid palatal expansion and intrusion of maxillary incisors both produce extrusion of posterior teeth, this study was undertaken to determine if a combination of controlled forces could prevent undesirable increases in vertical dimension. The maxillae were widened approximately 8 mm, the incisors were intruded 3 mm, the maxillary molars stayed the same or were intruded slightly, and the mandibular plane angle stayed essentially the same. In addition, A-point was retracted slightly and the occlusal plane was rotated in a counter-clockwise direction.