The relation of the formation of lipofuscin to the distribution of oxidative enzymes in the human brain
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Summary
The extent of deposition of lipofuscin in 66 nuclei of the aged human brain was classified systematically and the data were compared with the distribution of certain oxidative enzymes (succinic dehydrogenase, DPN-diaphorase). Nerve cells characterized by strong activity of oxidative enzymes in their perikarya contained more lipofuscin in aged brains than nerve cells characterized by little enzyme activity. The normal gradations of enzymatic (and probably metabolic) activity among cells thus predetermined—to a certain extent—the later deposition of lipofuscin. The lipofuscin in the neuropil (dendrite branchings) did not show the clear-cut relation to enzyme activity which characterized the perikarya; there was some indication of removal of lipofuscin from neuropil.
A correlation between functional activity, oxidative enzymatic activity and deposition of lipofuscin was suggested by the findings in two cases in which, following the removal of one eye, alternate layers of the lateral geniculate nucleus showed a marked decrease of DPN-diaphorase activity and decreased presence of lipofuscin. The presence of “wear and tear” pigment, therefore, appeared related to the functional “wear and tear” of a given region which is reflected by the intensity of oxidative metabolism. Cytological studies, on the other hand, did not imply a more specific association of lipofuscin with oxidative enzyme activity.
Keywords
Human Brain Nerve Cell Oxidative Metabolism Succinic Dehydrogenase Strong ActivityZusammenfassung
Das Ausmaß der Lipofuscinablagerung in 66 Kernen des gealterten menschlichen Gehirns wurde systematisch klassifiziert und die Ergebnisse wurden mit der Verteilung gewisser oxydativer Enzyme (Succinodehydrogenase, DPN-diaphorase) verglichen. Nervenzellen mit starker Aktivität der oxydativen Enzyme in den Perikarya wiesen mit zunehmendem Alter größere Lipofuscinansammlungen auf als Nervenzellen mit geringer Aktivität in den Perikarya. Daraus ist zu sehen, daß die Menge der späteren Lipofuscinablagerungen in gewissem Maße durch die normalen Unterschiede zwischen der enzymatischen (und vielleicht metabolischen) Tätigkeit der einzelnen Zellen bestimmt wird. Das im Neuropil (in den Dendritenverzweigungen) gebildete Lipofuscin scheint aus dem Gewebe abtransportiert zu werden; es zeigt daher nicht das deutlich sichtbare Verhältnis zur Enzymaktivität, wie es für die Perikarya charakteristisch ist.
Die Annahme einer Verbindung zwischen funktioneller Aktivität, der Aktivität von oxydativen Enzymen und späteren Lipofuscinablagerungen werden durch Befunde bei 2 Fällen nahegelegt, bei denen nach Entfernung eines Auges die alternierenden Schichten des Nucleus geniculatus lateralis eine beträchtlich verminderte DPN-diaphorase-Tätigkeit und verminderte Lipofuscinablagerung zeigten. Die Bildung von „Abnützungs”-Pigment scheint daher in Abhängigkeit von der funktionellen „Abnützung” einer bestimmten Region zu stehen, wobei sich diese Abnützung in der Intensität des oxydativen Stoffwechsels widerspiegelt. Andererseits weisen cytologische Studien auf keine nähere Beziehung des Lipofuscins zur oxydativen Enzymaktivität hin.
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