Presymptomatic glutamate levels in prefrontal cortex in the Hdh(CAG150) mouse model of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disorder with few available treatments. Clinical observations suggest prefrontal dysfunction in early stages of HD is associated with altered glutamate transport. Evidence from the R6/2 mouse model suggests an abnormal increase in glutamate signaling in the sensorimotor cortex and striatum. OBJECTIVE: The present study was designed to determine if a similar deficit in glutamate function occurs in the prefrontal cortex (PFC) of Hdh(CAG150) mice. METHODS: We used the following groups of 40 week old male and female Hdh(CAG150) mice: homozygote n = 7, heterozygote n = 7, wild type n = 6. Motor coordination was evaluated using a hanging wire grid test and a balance beam. Microdialysis measurements were taken from the PFC of freely moving mice while glutamate transporters were inhibited by L-trans-pyrrolidine-2, 4-dicarboxylate (PDC) and compared to baseline glutamate levels. RESULTS: RESULTS indicated an elevation in glutamate levels in response to PDC but no significant difference among genotype groups. When comparing wild type and homozygote alone, a significant difference in total extracellular glutamate was observed. Contrary to our original hypothesis, the homozygote group had lower glutamate levels compared to their wild type counterparts. Furthermore, there was a significant difference in GABA measurements across genotypes. CONCLUSIONS: Our results suggest a mechanistic dichotomy between R6/2 and Hdh(CAG150) mice and underscores the need to select the appropriate HD mouse model when assessing therapeutic interventions. In particular, the time when animals are evaluated can have a significant impact on behavioral and physiological measures and so should be carefully considered.

Case-control study of neurodevelopment in deformational plagiocephaly.

OBJECTIVE: We assessed the neurodevelopment of infants with and without deformational plagiocephaly (DP), at an average age of 6 months. METHODS: The Bayley Scales of Infant Development III (BSID-III) were administered to 235 case subjects and 237 demographically similar, control participants. Three-dimensional head photographs were randomized and rated for severity of deformation by 2 craniofacial dysmorphologists who were blinded to case status. RESULTS: We excluded 2 case subjects with no photographic evidence of DP and 70 control subjects who were judged to have some degree of DP. With control for age, gender, and socioeconomic status, case subjects performed worse than control subjects on all BSID-III scales and subscales. Case subjects' average scores on the motor composite scale were approximately 10 points lower than control subjects' average scores (P < .001). Differences for the cognitive and language composite scales were approximately 5 points, on average (P < .001 for both scales). In subscale analyses, case subjects' gross-motor deficits were greater than their fine-motor deficits. Among case subjects, there was no association between BSID-III performance and the presence of torticollis or infant age at diagnosis. CONCLUSIONS: DP seems to be associated with early neurodevelopmental disadvantage, which is most evident in motor functions. After follow-up evaluations of this cohort at 18 and 36 months, we will assess the stability of this finding. These data do not necessarily imply that DP causes neurodevelopmental delay; they indicate only that DP is a marker of elevated risk for delays. Pediatricians should monitor closely the development of infants with this condition.