Biomedical subjects

D R Kornack

Publications and source records attributed to D R Kornack.

7 recordsLinked to original sources

PubMed2001

Cell proliferation without neurogenesis in adult primate neocortex.

A recent assertion that new neurons are continually added to the neocortex of adult macaque monkeys has profound implications for understanding the cellular mechanisms of higher cognitive functions. Here we searched for neurogenesis in adult macaques by using immunofluorescent triple labeling for the DNA-replication indicator, bromodeoxyuridine (BrdU), and neuronal and glial cell markers. Although numerous BrdU-labeled cells were distributed throughout the cerebral wall, including the neocortex, these were identified as nonneuronal cells; evidence for newly generated neurons was limited to the hippocampus and olfactory bulb. Thus, our results do not substantiate the claim of neurogenesis in normal adult primate neocortex.

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PubMed2001

The generation, migration, and differentiation of olfactory neurons in the adult primate brain.

In adult rodents, neural progenitor cells in the subependymal (SZ) zone of the lateral cerebral ventricle generate neuroblasts that migrate in chains via the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into interneurons. However, the existence of this neurogenic migratory system in other mammals has remained unknown. Here, we report the presence of a homologue of the rodent SZ/RMS in the adult macaque monkey, a nonhuman Old World primate with a relatively smaller OB. Our results-obtained by using combined immunohistochemical detection of a marker for DNA replication (5-bromodeoxyuridine) and several cell type-specific markers-indicate that dividing cells in the adult monkey SZ generate neuroblasts that undergo restricted chain migration over an extended distance of more than 2 cm to the OB and differentiate into granule interneurons. These findings in a nonhuman primate extend and support the use of the SZ/RMS as a model system for studying neural regenerative mechanisms in the human brain.

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PubMed2000

Neurogenesis and the evolution of cortical diversity: mode, tempo, and partitioning during development and persistence in adulthood.

The mammalian cerebral cortex varies enormously in absolute and relative size across species. These size differences reflect phyletic differences in the number and organization of cortical neurons, which in turn imply evolutionary changes in the developmental program that generates these neurons. Whereas patterns of symmetric and asymmetric modes of progenitor cell division during cortical neurogenesis are widely conserved among species, other proliferation parameters, including the timing and number of cell divisions, vary considerably. This variation contributes to the development of cortical size differences in mammals in general, and the expansion of neocortex in anthropoid primates (monkeys, apes, and humans) in particular. The disproportionate enlargement of anthropoid neocortex might also arise from regional 'border-shifting' within the embryonic telencephalon, causing expansion of the neurogenic region allocated for producing neocortex and concomitant diminution of neighboring olfactory regions. Neurogenesis also shows substantial phyletic differences in adult hippocampus, an archicortical structure. Therefore, variation in neurogenesis across species is not only a feature of early development, but is also a trait of adult cortical diversity.

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PubMed1999

Continuation of neurogenesis in the hippocampus of the adult macaque monkey.

We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. Nevertheless, the generation of these three cell types in a discreet brain region suggests that a multipotent neural stem cell may be retained in the adult primate hippocampus. This demonstration of adult neurogenesis in nonhuman Old World primates-with their phylogenetic proximity to humans, long life spans, and elaborate cognitive abilities-establishes the macaque as an unexcelled animal model to experimentally investigate issues of neurogenesis in humans and offers new insights into its significance in the adult brain.

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PubMed1998

Changes in cell-cycle kinetics during the development and evolution of primate neocortex.

The evolutionary expansion of neocortical size in mammals is particularly prominent in anthropoid primates (i.e., monkeys, apes, and humans) and reflects an increased number of cortical cells, yet the developmental basis for this increase remains undefined. Cortical cell production depends on the length of the cell-division cycle of progenitor cells during neurogenesis, which previously has been measured only in smaller-brained rodents. To investigate whether cortical expansion in primates reflects modification of cell-cycle kinetics, we determined cell-cycle length during neurogenesis in the proliferative cerebral ventricular zone of fetal rhesus monkeys, by using cumulative S-phase labeling with bromodeoxyuridine. Cell-cycle durations in monkeys were as much as 5 times longer than those reported in rodents. Nonetheless, substantially more total rounds of cell division elapsed during the prolonged neurogenetic period of the monkey cortex, providing a basis for increased cell production. Moreover, unlike the progressive slowing that occurs during cortical development in rodents, cell division accelerated during neurogenesis of the enlarged cortical layers in monkeys. These findings suggest that evolutionary modification of the duration and number of progenitor cell divisions contributed to both the expansion and laminar elaboration of the primate neocortex.

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PubMed1995

Radial and horizontal deployment of clonally related cells in the primate neocortex: relationship to distinct mitotic lineages.

To analyze cell lineage in the rhesus monkey necorotex, we used recombinant retroviruses to label individual progenitor cells in the ventricular zone (VZ), then determined histochemically the distribution of their progeny during and after the period of cortical neurogenesis. Distribution patterns of labeled cells in the VZ suggested the coexistence of asymmetrically and symmetrically dividing progenitor cells, indicating that both postmitotic and mitotic progeny are produced during cortical neurogenesis. In the cortex, several distinct patterns of clonal distribution were observed and interpreted as follows: clones aligned radially suggested that asymmetrically dividing progenitors generate sequential "siblings" that migrate, in tandem, along a common radial path to the cortex. In contrast, clones oriented horizontally within a single lamina suggested that symmetric divisions produce multiple, laterally displaced progenitors which, in turn, simultaneously generate "cousin" cells that migrate, in concert, to the same cortical layer. Thus, we propose that different mitotic lineages, which coexist in the monkey VZ, produce distinct radial or laminar patterns of clone deployment that foreshadow the cytological organization of the adult neocortex.

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PubMed1991

Sexually dimorphic expression of the NGF receptor gene in the developing rat brain.

To define relations between trophic molecules and known sexually dimorphic traits in brain, we examined possible sex differences in nerve growth factor (NGF) and NGF receptor (NGF-R) gene expression in the rat cholinergic basal forebrain (BF)-hippocampal system. Hippocampal NGF mRNA levels did not differ between sexes; in contrast, BF NGF-R mRNA levels were greater in neonatal females than males, paralleling the known dimorphic development of cholinergic enzyme activity. Cerebellar NGF-R mRNA levels were also dimorphic in the neonate, suggesting that sex-specific influences may regulate trophic receptor gene expression in diverse brain systems.

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