Morphological and molecular changes in aging rat prelimbic prefrontal cortical synapses.
Age-related impairments of executive functions appear to be related to reductions of the number and plasticity of dendritic spine synapses in the prefrontal cortex (PFC). Experimental evidence suggests that synaptic plasticity is mediated by the spine actin cytoskeleton, and a major pathway regulating actin-based plasticity is controlled by phosphorylated LIM kinase (pLIMK). We asked whether aging resulted in altered synaptic density, morphology, and pLIMK expression in the rat prelimbic region of the PFC. Using unbiased electron microscopy, we found an approximate 50% decrease in the density of small synapses with aging, while the density of large synapses remained unchanged. Postembedding immunogold revealed that pLIMK localized predominantly to the postsynaptic density where it was increased in aging synapses by approximately 50%. Furthermore, the age-related increase in pLIMK occurred selectively within the largest subset of prelimbic PFC synapses. Because pLIMK is known to inhibit actin filament plasticity, these data support the hypothesis that age-related increases in pLIMK may explain the stability of large synapses at the expense of their plasticity.
Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Erik B
EB
Bloss
Rishi
R
Puri
Frank
F
Yuk
Michael
M
Punsoni
Yuko
Y
Hara
William G
WG
Janssen
Bruce S
BS
McEwen
John H
JH
Morrison
D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D005786:Gene Expression Regulation; D054461:Lim Kinases / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology*; D057907:Post-Synaptic Density / Q000378:metabolism / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure*
D054461:Lim Kinases