Age-Based Comparison of Human Dendritic Spine Structure Using Complete Three-Dimensional Reconstructions

Abstract

Dendritic spines of pyramidal neurons are targets of most excitatory synapses in the cerebral cortex. Recent evidence suggests that the morphology of the dendritic spine could determine its synaptic strength and learning rules. However, unfortunately, there are scant data available regarding the detailed morphology of these structures for the human cerebral cortex. In the present study, we analyzed over 8900 individual dendritic spines that were completely 3D reconstructed along the length of apical and basal dendrites of layer III pyramidal neurons in the cingulate cortex of 2 male humans (aged 40 and 85 years old), using intracellular injections of Lucifer Yellow in fixed tissue. We assembled a large, quantitative database, which revealed a major reduction in spine densities in the aged case. Specifically, small and short spines of basal dendrites and long spines of apical dendrites were lost, regardless of the distance from the soma. Given the age difference between the cases, our results suggest selective alterations in spines with aging in humans and indicate that the spine volume and length are regulated by different biological mechanisms.

What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus

“…Dendritic spines may represent a primary site of structural plasticity in the adult brain, and spine plasticity seems to play an important role in long-term memory in rodents (Sanders et al, 2012). Dendritic spine plasticity in the prefrontal cortex is reduced in aged rodents (Bloss et al, 2011), and spine density is likely reduced in aging (Jacobs et al, 1997, Esiri, 2007, Freeman et al, 2008, Benavides-Piccione et al, 2013) (see Figure 13). …”

“…Benavides-Piccione et al (2013) 3D reconstructed 8900 individual dendritic spines from layer III pyramidal neurons in the cingulate cortex from two male humans of age 40 and 85 years, using intracellular injections of Lucifer Yellow in fixed tissue. The left two panels show the 3D reconstruction of the complete morphology of each spine of an apical dendritic segment at 100 μm distance from the soma, and the estimation of the spine volumes shown in color codes (0–1.345 μm 3 ).…”

“…The differences in spine morphology are easily seen. Figure modified with permission from (Benavides-Piccione et al, 2013). …”

Is Timing Everything? A Meeting Report of the Society for Women's Health Research Roundtable on Menopausal Hormone Therapy

“…Loss of dendritic spines in the synapses of the prefrontal cortex is correlated with cognitive decline and may precede AD as well, though this is still a matter of intense study and investigation. 22,23 Estrogen receptors are present in excitatory synapses in the prefrontal cortex, 24 and it has been shown that estradiol enhances cognitive performance in nonhuman primates through partial restoration of the thin spines. 24 Thus, estrogen receptors and related signaling pathways may provide therapeutic targets for cognitive decline.…”

Brain functional connectivity in regions that exhibit age-related cortical thinning

“…Changes in synapses and spines and cell body shrinking have been put forward as hypotheses to describe these phenomena (FJELL et al, 2015d). In the case of spines, a major decrease in spines has been observed, regardless of the distance to the neuron body, in the comparison of the cingulate cortex of a middle-aged and an older adult (BENAVIDES-PICCIONE et al, 2013). Increases in glia and small-body neurons and decreases in large cell-body neurons populations are also observed throughout aging, contributing to a near constant cell density (MARTÍNEZ-PINILLA et al, 2016;TERRY;DETERESA;HANSEN, 1987).…”