3D neuronal mitochondrial morphology in axons, dendrites, and somata of the aging mouse hippocampus

Faitg, Julie; Lacefield, Clay; Davey, Tracey; White, Kathryn; Laws, Ross; Kosmidis, Stylianos; Reeve, Amy K.; Kandel, Eric R.; Vincent, Amy E.; Picard, Martin

doi:10.1016/j.celrep.2021.109509

Cited by 83 publications

(81 citation statements)

References 50 publications

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“…While most ssTEM techniques require skill and are labor-intensive, FIB-SEM, SBF-SEM, and ATUM-SEM are automatized and provide high-resolution 3D images [ 16 , 52 , 53 , 54 ] dramatically improving the interpretation of the morphology of tissue and cell samples. Amira software and other similar software ( Supplementary Table S7 ) can be used for FIB-SEM, SBF-SEM, and ATUM-SEM images [ 23 , 56 , 57 , 58 ]. For studies with large samples, SBF-SEM is faster and offers larger fields of view than FIB-SEM [ 54 ]: thus, we combined SBF-SEM with the versatility, ease of use, and features of the Amira software for analysis of the SBF-SEM images.…”

Section: Discussionmentioning

confidence: 99%

Protocols for Generating Surfaces and Measuring 3D Organelle Morphology Using Amira

Garza-López¹,

Vue

Katti

et al. 2021

Cells

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High-resolution 3D images of organelles are of paramount importance in cellular biology. Although light microscopy and transmission electron microscopy (TEM) have provided the standard for imaging cellular structures, they cannot provide 3D images. However, recent technological advances such as serial block-face scanning electron microscopy (SBF-SEM) and focused ion beam scanning electron microscopy (FIB-SEM) provide the tools to create 3D images for the ultrastructural analysis of organelles. Here, we describe a standardized protocol using the visualization software, Amira, to quantify organelle morphologies in 3D, thereby providing accurate and reproducible measurements of these cellular substructures. We demonstrate applications of SBF-SEM and Amira to quantify mitochondria and endoplasmic reticulum (ER) structures.

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Section: Discussionmentioning

confidence: 99%

Protocols for Generating Surfaces and Measuring 3D Organelle Morphology Using Amira

Garza-López¹,

Vue

Katti

et al. 2021

Cells

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“…The results herein revealed that the reduction of mitochondrial respiratory complex activity in the aged hippocampus was inconsistent with a previous report [ 21 ]. Recent 3D electron microscopic study demonstrated that mitochondrial morphology in different compartments of CA-1 and dentate gyrus neurons changed with aging [ 22 ]. Stimulating mitochondrial genesis and enhancing complex activity have been thought as efficient ways of developing antiaging medicine.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Mitochondrial Transplantation Alleviates Age-Associated Cognitive Decline via Enhancing Wnt Signaling and Neurogenesis

Zhang

Wei

et al. 2022

Computational Intelligence and Neuroscience

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Gradual cognition decline and mitochondrial dysfunction are two notable changes closely associated with aging. Enhancing mitochondrial function has been assumed to be antiaging. However, most current mitochondria-promoting agents usually target 1-2 aspects of mitochondrial function. In the present study, we transplanted mitochondria isolated from young mice into the hippocampus of aged mice, which presumably boost mitochondrial function more thoroughly, examined the effects on cognition, and explored the possible underlying mechanism. Our data showed that exogenous mitochondria were efficiently internalized by nestin-positive neural progenitors in the hippocampus. Mitochondrial transplantation quickly increased ATP levels, enhanced the activity of mitochondrial complexes I, II, and IV, and decreased Tom20 expression in the hippocampus. In regard of cognitive function, mitochondria-treated mice displayed a remarkable improvement of novel object recognition and spatial memory. Utilizing the Wnt signaling reporting mouse line, TOPGAL mice, we detected activated canonical Wnt signaling in the neural progenitors of the mitochondria-treated hippocampus. Further, BrdU labeling showed that exogenous mitochondria significantly stimulated neural progenitor neurogenesis and proliferation. Taken together, our data demonstrated that exogenous mitochondria from young mice might be a novel way of rejuvenating the function of hippocampal neural progenitors to exert antiaging effects.

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“…This heterogeneity makes the gastrocnemius ideal to study changes in mitochondrial dynamics. Other studies on the effects of aging on mitochondria in human and mouse skeletal muscle have focused on mitochondrial mutations 18 . Our 3D reconstruction of aged skeletal gastrocnemius muscle is a novel approach to study the connections between mitochondria and to determine how disconnections and reduced mitochondrial communication impact oxidative phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

3D Reconstruction of Murine Mitochondria Exhibits Changes in Structure Across Aging Linked to the MICOS Complex

Vue

Lopez

Neikirk

et al. 2022

Preprint

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Background: Skeletal muscle gradually loses mass, strength, endurance, and oxidative capacity during aging. Studies of bioenergetics and protein turnover show that mitochondria mediate this decline in function. Mitochondria are essential for the production of ATP, which occurs in the cristae, the folds of the inner mitochondrial membrane. While mitochondrial aging is associated with endoplasmic reticulum stress, fragmented mitochondria, and decreased mitochondrial capacity, the genes associated with morphological changes in mitochondria during aging are unknown. Further, we do not understand how 3D mitochondrial networks and the specialization of mitochondria alter during aging. Methods: We measure changes in mitochondrial morphology and mitochondrial connectivity during the aging of the mouse gastrocnemius muscle through serial block facing-scanning electron microscopy and 3D reconstruction. Nanotunnels are also measured through 3D reconstruction. CRISPR/Cas9 KD is performed to examine changes in mitochondria upon loss of MICOS complex and OPA-1. Metabolomics are used to find key metabolite pathways changed upon MICOS complex loss. Results: We found changes in mitochondrial network configuration, nanotunneling, size, shape, number, contact sites, and cristae organizing system (MICOS) dynamics and gene expression in skeletal muscle across aging. Cardiac muscle showed similar differences but less fragmentation and wide-spread changes across 2-year aaging. We also found an association of optic atrophy 1 (OPA-1) and the MICOS complex in the gastrocnemius with mitochondrial aging, decreased oxidative capacity, and altered mitochondrial metabolism. Conclusions: We are the first to examine mitochondria changes in skeletal muscle and cardiac muscle across aging. 3D reconstructions of nanotunnels elucidated novel patterns in skeletal muscle. Notably, we noticed differences in skeletal and cardiac muscle that suggests a differential response to mitochondrial aging in cardiac and skeletal muscle. Importantly, we found similar changes in mitochondrial morphology were observed in aging skeletal muscles and for loss of MICOS proteins in mouse skeletal muscle. Furthermore, MICOS proteins decreased with age. In tandem, this suggests a relationship between the MICOS complex and aging, which further 3D reconstruction could potentially further link to disease states.

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3D neuronal mitochondrial morphology in axons, dendrites, and somata of the aging mouse hippocampus

Cited by 83 publications

References 50 publications

Protocols for Generating Surfaces and Measuring 3D Organelle Morphology Using Amira

Protocols for Generating Surfaces and Measuring 3D Organelle Morphology Using Amira

Hippocampal Mitochondrial Transplantation Alleviates Age-Associated Cognitive Decline via Enhancing Wnt Signaling and Neurogenesis

3D Reconstruction of Murine Mitochondria Exhibits Changes in Structure Across Aging Linked to the MICOS Complex

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