Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration.
Amyloid-beta (Abeta) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer's disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Abeta, we administered the ROCK inhibitor fasudil to AbetaPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AbetaPP/PS1 mice and that fasudil promotes lengthening of the dendrite arbors of CA1 pyramidal neurons.
Couch
Brian A
BA
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
DeMarco
George J
GJ
Gourley
Shannon L
SL
Koleske
Anthony J
AJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D053764:Presenilin-1 / Q000235:genetics / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D053764:Presenilin-1; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; C049347:fasudil