title: Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.
abstract: Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the 'mitochondria-on-a-string' phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. Electronic address: Yury.morozov@yale.edu.
authors.forename: Yury M
authors.initials: YM
authors.lastname: Morozov
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Dibyadeep
authors.initials: D
authors.lastname: Datta
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Constantinos D
authors.initials: CD
authors.lastname: Paspalas
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. Electronic address: amy.arnsten@yale.edu.
authors.forename: Amy F T
authors.initials: AFT
authors.lastname: Arnsten
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D003712:Dendrites / Q000648:ultrastructure; D021621:Imaging, Three-Dimensional; D008253:Macaca mulatta; D064347:Microscopy, Electrochemical, Scanning; D008928:Mitochondria / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure*; D063154:Mitochondrial Dynamics; D009474:Neurons / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000473:pathology / Q000648:ultrastructure*
keywords: 3D reconstruction; Alzheimer's disease; Cognition; Electron microscopy; Mitochondrial dynamics; Primate brain aging