Dendritic spine changes associated with normal aging

Abstract

Given the rapid rate of population aging and the increased incidence of cognitive decline and neurodegenerative diseases with advanced age, it is important to ascertain the determinants that result in cognitive impairment. It is also important to note that much of the aged population exhibit 'successful' cognitive aging, in which cognitive impairment is minimal. One main goal of normal aging studies is to distinguish the neural changes that occur in unsuccessful (functionally impaired) subjects from those of successful (functionally unimpaired) subjects. In this review, we present some of the structural adaptations that neurons and spines undergo throughout normal aging and discuss their likely contributions to electrophysiological properties and cognition. Structural changes of neurons and dendritic spines during aging, and the functional consequences of such changes, remain poorly understood. Elucidating the structural and functional synaptic age-related changes that lead to cognitive impairment may lead to the development of drug treatments that can restore or protect neural circuits and mediate cognition and successful aging.

Keywords: ChAT; DG; DNMS; DRST; GluR; HCN; N-methyl-d-aspartate; NMDA; OVX; PFC; PKC; PSCs; SAMP; aging; cAMP; choline acetyltransferase; cognition; cyclic-AMP; delayed non-matching-to-sample; delayed recognition span test; dendritic spines; dentate gyrus; electrophysiology; glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated; morphology; ovariectomized; postsynaptic currents; prefrontal cortex; protein kinase C; senescence-prone strains.

Figure 1

Age-related morphologic changes of layer 3 neocortical pyramidal neurons forming long and local projections in rhesus monkeys. (A) Total length of dendrites from the apical and basal arbors of long projection (from superior temporal cortex to PFC) and locally projecting neurons (within PFC). (B) The total number of spines per neuron (top) and average spine density (bottom) on apical and basal dendrites of long projection and locally projecting neurons. Data from young and aged monkeys are shown in black and white respectively. (*p < 0.05; **p < 0.01). Data summarized from Kabaso et al. (2009).

Figure 2

Representative dendritic segments and spines from layer 3 pyramidal neurons from PFC of young (left) and aged (right) rhesus monkeys. Top row shows segments from the apical arbor; bottom row from the basal arbor. These are xy-projections of confocal laser scanning microscopy images (40X, 1.5 digital zoom), after deconvolution.