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Sources: Gould E, et al. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 1999;2:260-265. van Praag H, et al. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999;2:266-270. Eriksson PS, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998;4:1313-1317. Wickelgren I. Nurture helps mold able minds. Science 1999;283:1832-1834.
New remarkable findings in basic neuroscience promise future opportunities to treat damaged brains and lengthen the life of the chronically stimulated ones (McKay RD. Nat Med 1999;5:261-262). Until a few years ago, neuroscience dogma had clung to the principle that human, postnatal brains could not generate new neurons, much less accept neuronal transplants. Between 1975-1985, evidence that the human olfactory receptor system turned over its neurons at a rate of about two weeks was almost completely ignored (Kaplan MS, Hinds JW. Science 1977;197: 1092-1094). Similar inattention was directed at observations made by McKay that premordial granular cells in the cerebellum and the hippocampus apparently generated new neurons in experimental mammals. The success of transplanting fetal nigral cells from human fetuses into Parkinsonian striatums broke the ice of wide ignorance, but only recently has the evidence proved that:
1) continuous hippocampal neurogenesis occurs normally throughout human life;
2) neurogenesis increases in nonprimate animals at a rate greatly accelerated by optimal environments and stimulating the species by appropriate problem-solving tasks;
3) the human brain contains stem cells that have the capacity not only to generate progenitor central nervous system neurons but, given the appropriate environment, hematopoeitic cells as well (McKay).
Gould and associates (Proc Natl Acad Sci USA 1998;95:3168-3171) have identified newly produced hippocampal cells in monkeys and, most recently, van Praag and associates from the Sahlgrenska Hospital in Goteborg, Sweden, along with Eriksson and associates from Fred Gage’s laboratory at the Salk Institute, have made a similar discovery in humans. The Gould et al primate study brings out evidence that granular precursor cells in the dentate gyrus of the hippocampus constantly and normally produce new mature neurons at a relatively steady state. Neurogenesis and differentiation of neurons measurably declined, however, when the animals were exposed to regulated degrees of acute psychosocial stress (similar responses to stress have been identified in hippocampal regions in rodents). Eriksson et al describe findings in five humans dying of cancer who were free of severe brain disease, but steadily generated new hippocampal granular neurons. Evidence is that hippocampus neurogenesis is not related to those patients because of their cancer; rather, the cohort was chosen because at present neurogenesis can only be identified by scheduled future brain biopsy or permission for autopsy within a few years.
The technical approach for identifying the above depends on marking granulomatous stem cells in the hippocampus with the stable thymidine analog, bromodeoxyuridine (BrdU). The BrdU enters the DNA of hippocampal stem cells that subsequently divide into neurons carrying permanent DNA markers. Such cells can be identified almost indefinitely throughout the recipient’s natural life. Eriksson et al’s paradigm consisted of infusing BrdU into five patients with malignant systemic cancers, none of whom showed evidence of involvement of the brain. The patients were expected to die within a measurable time, which actually ranged from 16-781 days following systemic BrdU injection. Intensity of stained (progeny) neurons was greatest in patients dying at 16 and 136 days after injection, but the other three also demonstrated newly engendered hippocampal neurons, the latest being 781 days after the initial injection. The subventricular zone adjacent to the caudate nucleus did not generate BrdU neurons, but did generate round-to-oval progenitor neurons, presumably as the cells migrated closer to the olfactory system.
Although not conducted in humans, the two index articles by van Pragg et al and Gould et al report that hippocampal neurogenesis as much as doubled in rodents put to enriching or associative-learning tasks. Presumably, the increased neuronal numbers contributed to the memory of the rewards gained by learned activity.
In an additional report by Young and associates (Young D, et al. Nat Med 1999;5:448-453), they report that rodents, a species that has consistently anticipated the finding of brain regeneration in higher mammals, reduce potential apoptosis in post-traumatic hippocampus when enriched by environment in situ neurogenesis depends.
These experimental findings in the hippocampus of lower level mammals and humans imply that this structure normally generates throughout adult life new granular neurons that may closely contribute to processed learning and memory. Furthermore, evidence gained from trained rodents suggests that stimulating the animal accelerates the genesis of new cells and new memories, and also may reduce traumatic induced apoptosis. Carrying such a possibility into clinical action, these favorable events especially occur in young animals. A "News Focus" article in Science by Ingrid Wickelgren reports that underprivileged children who receive systematic lessons in language and enrichment in complex problems suitable to their age (i.e., as young as 6 months) later attain IQ values far higher than those possessed by their parents as well as by other neighborhood children. The report provides evidence from many other sources which indicate that the younger children start and the more persistently that they are taught appreciably raises their later intelligence. This conclusion suggests that early, sustained stimulation of an infant’s/child’s hippocampus, the smarter and more capable their futures are likely to be. Only a few months ago, Neurology Alert (Plum F. Neurol Alert 1998;16:94-95) abstracted a study from Neurology (De Ronchi D, et al. Neurology 1998;50:1231-1238) that linked early senile dementia to a lack of sufficient childhood education to gain literacy. Hopefully, knowing the scientific data abstracted in these present reports may stimulate neurologists to lead their communities to emphasize the value of environmental and educational programs for all children aged 2 years or older. It appears that such a step will pay off with enriching hippocampal activity, thereby reducing the number of unemployed or the incidence of late dementia in the society. Who knows, such early teaching of the child’s mind might reduce its seeming intoxications with violence.
a. Adult human brains do not normally generate new brain neurons after age 12 years.
b. Structured teaching of children between ages 2-5 may significantly and permanently increase their I.Q.
c. Brain stem cells are rare and explicitly targeted at specific areas of the organ.
d. Brain stem cells are not capable of generating progenitor cells for other tissues of the body.