Morphological plasticity of synaptic mitochondria during aging

A morphometric investigation has been carried out on the synaptic mitochondria of cerebellar glomeruli in young, adult and old rats by means of a computer-assisted image analysis technique. Mitochondrial volume density (Vv), numerical density (Nv), average volume (V) and average length (Skeleton = Sk) were investigated in tissue samples fixed, embedded and sectioned according to conventional electron microscopic methods. Vv was unchanged in the three groups of age taken into account. Nv was significantly increased in adult vs. young animals, whereas it was decreased in the old group as compared to both the other two groups investigated. V and Sk showed the same age-dependent changes: they significantly decreased in the adult vs. the young and the old groups of rats while increased significantly in the old rats vs. both the adult and young animals. A percentage distribution of Sk demonstrated that in the old group 20.6% of the population of synaptic mitochondria accounts for elongated organelles (> 5 microns) as compared to 8.6% and 5.3% in young and adult animals, respectively. The present findings match the changes previously reported by us on the ultrastructure of synaptic contact zones both in rats and human beings, and support the idea of an age-dependent dynamic adaptation in the morphology of synaptic mitochondria to cope with the metabolic needs of the pattern of synaptic connectivity they subserve.

[1]  J. Clark,et al.  SYNAPTIC AND NON‐SYNAPTIC MITOCHONDRIA FROM RAT BRAIN: ISOLATION AND CHARACTERIZATION , 1977, Journal of neurochemistry.

[2]  C. Cotman,et al.  Synaptic Plasticity and Aging , 1990 .

[3]  V. Egilsson,et al.  Mitochondria, cell surface, and carcinogenesis. , 1983, International review of cytology. Supplement.

[4]  R. Hansford Bioenergetics in aging. , 1983, Biochimica et biophysica acta.

[5]  J. Shay,et al.  Are mitochondrial DNA mutations involved in the carcinogenic process? , 1987, Mutation research.

[6]  Carolyn B. Smith Aging and changes in cerebral energy metabolism , 1984, Trends in Neurosciences.

[7]  R. Floyd,et al.  Age-dependent changes in rat brain mitochondria of synaptic and non-synaptic origins , 1987, Mechanisms of Ageing and Development.

[8]  W. Meier-Ruge,et al.  Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease , 1990, Brain Research.

[9]  J. Vitorica,et al.  Differential effects of age on the pathways of calcium influx into nerve terminals , 1987, Brain Research.

[10]  Sohal Rs,et al.  Effects of experimental alterations in phospholipid composition on the size and number of mitochondria in the flight muscles of the housefly, Musca domestica. , 1977 .

[11]  G. Schatz,et al.  The biogenesis of mitochondria. , 1970, The Biochemical journal.

[12]  R. Lasek,et al.  Mechanisms at the axon tip regulate metabolic processes critical to axonal elongation. , 1987, Progress in brain research.

[13]  C. Dell'orbo,et al.  Enzyme activities in perikaryal and synaptic mitochondrial fractions from rat hippocampus during development , 1989, Mechanisms of Ageing and Development.

[14]  C. Cotman,et al.  Synapse replacement in the nervous system of adult vertebrates. , 1981, Physiological reviews.

[15]  P Siekevitz,et al.  Plasticity in the central nervous system: do synapses divide? , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Patel,et al.  Age-dependent changes in pyruvate uptake by nonsynaptic and synaptic mitochondria from rat brain , 1982, Mechanisms of Ageing and Development.

[17]  R. Farrar,et al.  Reduced calcium uptake by rat brain mitochondria and synaptosomes in response to aging , 1985, Brain Research.

[18]  R. K. S. Calverley,et al.  Contributions of dendritic spines and perforated synapses to synaptic plasticity , 1990, Brain Research Reviews.

[19]  Michael C. J. Chang,et al.  The lipid composition of mitochondrial outer and inner membranes from the brains of goldfish acclimated at 5 and 30°C , 1989 .

[20]  G. Benzi,et al.  Age-related modifications of cytochrome c oxidase activity in discrete brain regions , 1990, Mechanisms of Ageing and Development.

[21]  L. Grinna Age related changes in the lipids of the microsomal and the mitochondrial membranes of rat liver and kidney , 1977, Mechanisms of Ageing and Development.

[22]  Y. Minaire,et al.  Great adaptability of brown adipose tissue mitochondria to extreme ambient temperatures in control and cold-acclimated gerbils as compared with mice. , 1988, Comparative biochemistry and physiology. B, Comparative biochemistry.

[23]  B. Grafstein,et al.  Intracellular transport in neurons. , 1980, Physiological reviews.

[24]  R. Menzies,et al.  The turnover of mitochondria in a variety of tissues of young adult and aged rats. , 1971, The Journal of biological chemistry.

[25]  D. Hegner,et al.  Do mitochondria produce oxygen radicals in vivo? , 1978, European journal of biochemistry.

[26]  R. S. Sohal,et al.  Associated changes in the size and number of mitochondria present in the midgut of the larvae of the housefly, Musca domestica and phospholipid composition of the larvae. , 1978, Journal of cell science.

[27]  S. DeKosky,et al.  Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity , 1990, Annals of neurology.

[28]  W. Meier-Ruge,et al.  Quantitative morphology of synaptic plasticity in the aging brain. , 1988, Scanning microscopy.

[29]  A. Davison,et al.  Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? , 1990, Free radical biology & medicine.

[30]  J. Miquel An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells. , 1991, Archives of gerontology and geriatrics.

[31]  L. Sokoloff,et al.  RELATION BETWEEN PHYSIOLOGICAL FUNCTION AND ENERGY METABOLISM IN THE CENTRAL NERVOUS SYSTEM , 1977, Journal of neurochemistry.

[32]  S. Hoyer The effect of age on glucose and energy metabolism in brain cortex of rats. , 1985, Archives of gerontology and geriatrics.

[33]  M. Patel Age-dependent changes in the oxidative metabolism in rat brain. , 1977, Journal of gerontology.

[34]  K. Gaebel,et al.  Stereological analysis of mitochondria from brains of temperature acclimated goldfish, Carassius auratus L. (5 and 30°C) , 1989 .

[35]  J. Miquel,et al.  A two-step hypothesis on the mechanisms of in vitro cell aging: Cell differentiation followed by intrinsic mitochondrial mutagenesis , 1984, Experimental Gerontology.

[36]  A. Myers,et al.  Genetics of mitochondrial biogenesis. , 1986, Annual review of biochemistry.

[37]  K. Piehl,et al.  Mitochondrial volume in skeletal muscle from young and old physically untrained and trained healthy men and from alcoholics. , 1973, Clinical science.

[38]  D. Jones,et al.  Synaptic remodelling during development and maturation: junction differentiation and splitting as a mechanism for modifying connectivity. , 1984, Brain research.

[39]  R. S. Sohal,et al.  Hydrogen peroxide release by mitochondria increases during aging , 1991, Mechanisms of Ageing and Development.

[40]  C. Pieri,et al.  Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging , 1986, Brain Research.

[41]  Stephen W. Scheff,et al.  Quantitative assessment of cortical synaptic density in Alzheimer's disease , 1990, Neurobiology of Aging.

[42]  M. Rosenthal,et al.  Effects of age on brain oxidative metabolism in vivo , 1979, Brain Research.