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Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2.

Ansorg A, Witte OW, Urbach A - BMC Neurosci (2012)

Bottom Line: Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins.This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death.The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.

ABSTRACT

Background: Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons.

Results: Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters.

Conclusions: The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that adult neurogenesis continuously adds new neurons to the hippocampal network, hence increasing cell density of the DG.

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Adult cD2KO mice have reduced numbers of dentate granule cells (DGCs). Absolute numbers of DGCs were estimated in mice aged P88 or P288. At both ages, they were significantly reduced due to the lack of functional cD2 (*p < 0.001). In WT animals, the number of DGCs increased with advancing age (#p < 0.05). We found no evidence for such an age-related change in cD2KO mice.
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Figure 4: Adult cD2KO mice have reduced numbers of dentate granule cells (DGCs). Absolute numbers of DGCs were estimated in mice aged P88 or P288. At both ages, they were significantly reduced due to the lack of functional cD2 (*p < 0.001). In WT animals, the number of DGCs increased with advancing age (#p < 0.05). We found no evidence for such an age-related change in cD2KO mice.

Mentions: The total number of DGCs in adult animals differed significantly between WT and cD2KO mice (Figure 4). At P88, cD2KO mice had ~60% fewer DGCs than their WT litters (WT: 1006057 ± 79843, cD2KO: 406455 ± 28201; p < 0.001). At P288, the number of DGCs in cD2KO mice was ~65% lower as compared to WT mice (WT: 1179307 ± 36738, cD2KO: 409150 ± 35489; p < 0.001). Moreover, the number of DGCs in WT, but not in cD2KO mice, increased between P88 and P288 (p = 0.032). For all animals the CE fell below 0.05.


Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2.

Ansorg A, Witte OW, Urbach A - BMC Neurosci (2012)

Adult cD2KO mice have reduced numbers of dentate granule cells (DGCs). Absolute numbers of DGCs were estimated in mice aged P88 or P288. At both ages, they were significantly reduced due to the lack of functional cD2 (*p < 0.001). In WT animals, the number of DGCs increased with advancing age (#p < 0.05). We found no evidence for such an age-related change in cD2KO mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403990&req=5

Figure 4: Adult cD2KO mice have reduced numbers of dentate granule cells (DGCs). Absolute numbers of DGCs were estimated in mice aged P88 or P288. At both ages, they were significantly reduced due to the lack of functional cD2 (*p < 0.001). In WT animals, the number of DGCs increased with advancing age (#p < 0.05). We found no evidence for such an age-related change in cD2KO mice.
Mentions: The total number of DGCs in adult animals differed significantly between WT and cD2KO mice (Figure 4). At P88, cD2KO mice had ~60% fewer DGCs than their WT litters (WT: 1006057 ± 79843, cD2KO: 406455 ± 28201; p < 0.001). At P288, the number of DGCs in cD2KO mice was ~65% lower as compared to WT mice (WT: 1179307 ± 36738, cD2KO: 409150 ± 35489; p < 0.001). Moreover, the number of DGCs in WT, but not in cD2KO mice, increased between P88 and P288 (p = 0.032). For all animals the CE fell below 0.05.

Bottom Line: Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins.This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death.The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.

ABSTRACT

Background: Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons.

Results: Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters.

Conclusions: The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that adult neurogenesis continuously adds new neurons to the hippocampal network, hence increasing cell density of the DG.

Show MeSH
Related in: MedlinePlus