Ultrastructural analysis of the cellular distribution of mitochondria in cholinergic basal forebrain neurons during aging in the mouse

Previous results from our laboratory have demonstrated disruption in calcium (Ca2+) signaling in cholinergic neurons of the rat basal forebrain during aging (J. Neurophysiol. 102: 2194–2207, 2009). One mechanism that could contribute to these age‐related changes is the ability of mitochondria to buffer intracellular Ca2+ concentrations. The purpose of this study was to utilize electron microscopy (EM) to examine the size and location of mitochondria within cholinergic neurons in the basal forebrain in mice of different ages. We hypothesized that mitochondrial size, location and number would increase during aging and this increase would be greatest in cholinergic neurons. A total of 12 mice, 6 young (3–6 mo) and 6 aged (>20 mo), were perfused, their brains sectioned and stained with diaminobenzidine (DAB) immunohistochemistry, which was used to identify cholinergic neurons. After plastic embedding and detailed EM analysis, we found that the relative mitochondrial size increased with age with no difference between cholinergic and noncholinergic neruons. There was no change in mitochondrial number, although mitochondria were located closer to the plasma membrane in aged neurons (p=0.03). All of these results suggest that changes in mitochondrial size and location could contribute to altered Ca2+ signaling during aging. Grant Funding Source : NIH Grant AG007805