Neocortical vasculature abnormalities in the Fragile X mental retardation syndrome.
The Fragile X syndrome (FXS) is the leading form of inherited mental retardation. To date, the most prominent neuronal phenotype associated with the syndrome is an abundance of long thin spines exhibiting an immature morphology. However, in addition to synaptic abnormalities, recent case studies have demonstrated that Fragile X (FX) patients also exhibit abnormal cerebral blood flow (CBF). To examine the role of the Fragile X mental retardation protein (FMRP) in altering CBF, we examined blood vessel density (BVD) in the visual cortex of Adult and Middle-aged FX mice. Analysis of Middle-aged FX mice demonstrated elevated BVD compared to wildtype controls, suggesting that FX mice exhibit a lack of age-induced BVD plasticity. However, Adult FX and wildtype mice did not exhibit consistent differences in BVD. These data demonstrate that FMRP is required for age-induced neocortical vasculature plasticity. Furthermore, these data suggest a new role for FMRP in blood vessel regulation that would have profound implications towards appropriately timed delivery of neuronal nutrients, thus contributing to or exacerbating FX cognitive and neuronal abnormalities.
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405N Mathews Ave, Urbana, IL 61801, USA.
Ashley M
AM
Galvan
Roberto
R
Galvez
D000367:Age Factors; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000098:blood supply / Q000473:pathology*; D012039:Regional Blood Flow / Q000235:genetics; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*
D024141:Collagen Type IV; D003576:Electron Transport Complex IV; D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse