Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice.
Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. The specific function of this protein is unknown; however, it has been proposed to play a role in developmental synaptic plasticity. Examination of human brain autopsy material has shown that fragile-X patients exhibit abnormalities in dendritic spine structure and number, suggesting a failure of normal developmental dendritic spine maturation and pruning in this syndrome. Similar results using a knockout mouse model have previously been described; however, it was noted in retrospect that the mice used in that study may have carried a mutation for retinal degeneration, which may have affected cell morphology in the visual cortex of those animals. In this study, dendritic spines on layer V pyramidal cells of visual cortices, taken from fragile-X knockout and wild-type control mice without the retinal degeneration mutation and stained using the Golgi-Cox method, were investigated for comparison with the human condition. Quantitative analyses of the lengths, morphologies, and numbers of dendritic spines, as well as amount of dendritic arbor and dendritic branching complexity, were conducted. The fragile-X mice exhibited significantly more long dendritic spines and significantly fewer short dendritic spines than control mice. Similarly, fragile-X mice exhibited significantly more dendritic spines with an immature-like morphology and significantly fewer with a more mature type morphology. However, unlike the human condition, fragile-X mice did not exhibit statistically significant dendritic spine density differences from controls. Fragile-X mice also did not demonstrate any significant differences from controls in dendritic tree complexity or dendritic arbor. Long dendritic spines with immature morphologies are characteristic of early development or a lack of sensory experience. These results are similar to those found in the human condition and further support a role for the fragile-X mental retardation protein specifically in normal dendritic spine developmental processes. They also support the validity of these mice as a model of fragile-X syndrome.
Irwin
Scott A
SA
Neuroscience Program, University of Illinois, Urbana, Illinois 61801, USA.
Idupulapati
Madhuri
M
Gilbert
Molly E
ME
Harris
Jennifer B
JB
Chakravarti
Aparna B
AB
Rogers
Erica J
EJ
Crisostomo
Ralph A
RA
Larsen
Brian P
BP
Mehta
Amit
A
Alcantara
C J
CJ
Patel
Biraju
B
Swain
Rodney A
RA
Weiler
Ivan Jeanne
IJ
Oostra
Ben A
BA
Greenough
William T
WT
D000818:Animals; D003712:Dendrites / Q000473:pathology*; D005600:Fragile X Syndrome / Q000235:genetics / Q000473:pathology*; D006056:Golgi Apparatus / Q000473:pathology; D008607:Intellectual Disability / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology*; D017966:Pyramidal Cells / Q000473:pathology*; D014793:Visual Cortex / Q000473:pathology*