Possible new autosomal recessive syndrome of partial agenesis of the corpus callosum, pontine hypoplasia, focal white matter changes, hypotonia, mental retardation, and minor anomalies

Background: Clinical and epidemiologic studies suggest a relationship between long-term nano-particulate matter (nPM) exposure and white matter injury 1 . Accumulating laboratory evidence suggests that nPM exposure causes inflammation in multiple brain regions 2 . Objective: We sought to study the effects nano-particulate matter exposure on microglia activation and complement upregulation within the corpus callosum in a murine model. Methods: C57 black 6J mice were randomized to re-aerosolized nPM (n=18, nPM <200 nm) or filtered air (n=18) cohorts. Exposures were conducted for a total of 150 cumulative hours. Post-exposure, brains were harvested and immunohistochemical analysis performed. Reactive microglia (IBA-1), reactive astrocytes (GFAP) and C5α deposition (C5α antibody) were quantified in the medial corpus callosum. Results: There were significant differences in IBA-1 cell count staining between the groups (filtered air- 94.7± 18.87; nPM- 158.5 ± 41.69, p<0.05). No differences in GFAP cell count staining existed between the filtered air (677.5 ± 96.09) and nPM mice (656.6 ± 120.3, p=ns). There were significant differences in C5α density staining between filtered air (8.181 ± 3.863) and nPM mice (14.77 ± 5.989, p<0.01). Conclusion: Chronic particulate matter exposure is associated with white matter changes in a murine model. Regional increases in microglia number and C5α deposition suggest an inflammatory mechanism. References: 1. Calderon-Garciduenas L, Mora-Tiscareno A, Ontiveros E, Gomez-Garza G, Barragan-Mejia G, Broadway J, Chapman S, Valencia-Salazar G, Jewells V, Maronpot RR, Henriquez-Roldan C, Perez-Guille B, Torres-Jardon R, Herrit L, Brooks D, Osnaya-Brizuela N, Monroy ME, Gonzalez-Maciel A, Reynoso-Robles R, Villarreal-Calderon R, Solt AC, Engle RW. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 2008;68(2):117-27. 2. Block, M. L., & Calderón-Garcidueñas, L. (2009). Air pollution: mechanisms of neuroinflammation and CNS disease. Trends in neurosciences , 32 (9), 506-516.

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Does the Framingham Stroke Risk Profile predict white-matter changes in late-life depression?

International Psychogeriatrics ◽

10.1017/s1041610211002183 ◽

2011 ◽

Vol 24 (4) ◽

pp. 524-531 ◽

Cited By ~ 16

Author(s):

Charlotte L. Allan ◽

Claire E. Sexton ◽

Ukwuori G. Kalu ◽

Lisa M. McDermott ◽

Mika Kivimäki ◽

...

Keyword(s):

White Matter ◽

Corpus Callosum ◽

Stroke Risk ◽

Late Life ◽

Risk Profile ◽

The Body ◽

White Matter Integrity ◽

Late Life Depression ◽

White Matter Changes ◽

Depressed Group

ABSTRACTBackground: Cardiovascular risk factors and diseases are important etiological factors in depression, particularly late-life depression. Brain changes associated with vascular disease and depression can be detected using magnetic resonance imaging. Using diffusion tensor imaging (DTI), we investigated whether the Framingham Stroke Risk Profile (FSRP), a well-validated risk prediction algorithm, is associated with changes in white-matter connectivity. We hypothesized that depressed participants would show reduced white-matter integrity with higher FSRP, and non-depressed controls (matched for mean vascular risk) would show minimal co-variance with white-matter changes.Methods: Thirty-six participants with major depression (age 71.8 ± 7.7 years, mean FSRP 10.3 ± 7.6) and 25 controls (age 71.8 ± 7.3 years, mean FSRP 10.1 ± 7.7) were clinically interviewed and examined, followed by 60-direction DTI on a 3.0 Tesla scanner. Image analysis was performed using FSL tools (www.fmrib.ox.ac.uk/fsl) to assess the correlation between FSRP and fractional anisotropy (FA). Voxelwise statistical analysis of the FA data was carried out using Tract Based Spatial Statistics. The significance threshold for correlations was set at p < 0.05 using threshold-free cluster-enhancement. Partial correlation analysis investigated significant correlations in each group.Results: Participants in the depressed group showed highly significant correlations between FSRP and FA within the body of corpus callosum (r = −0.520, p = 0.002), genu of corpus callosum (r = −0.468, p = 0.005), splenium of corpus callosum (r = −0.536, p = 0.001), and cortico-spinal tract (r = −0.473, p = 0.005). In controls, there was only one significant correlation in the body of corpus callosum (r = −0.473, p = 0.023).Conclusions: FSRP is associated with impairment in white-matter integrity in participants with depression; these results suggest support for the vascular depression hypothesis.

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