Impaired Generation of Transit-Amplifying Progenitors in the Adult Subventricular Zone of Cyclin D2 Knockout Mice

Płatek, Rafał; Rogujski, Piotr; Mazuryk, Jarosław; Wisniewska, M.; Kaczmarek, Leszek; Czupryn, Artur

doi:10.3390/cells11010135

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…A recent report also described reduced adult neurogenesis in the subventricular zone SVZ of the adult brain in D2 k.o. mice, resulting in reduced numbers of adult‐generated interneurons in the olfactory bulb (Płatek et al, 2022). Potentially, such reduction in adult neurogenesis outside the hippocampus might contribute to effects on individuality.…”

Section: Discussionmentioning

confidence: 99%

Loss of individualized behavioral trajectories in adult neurogenesis‐deficient cyclin D2 knockout mice

et al. 2023

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There is still limited mechanistic insight into how the interaction of individuals with their environment results in the emergence of individuality in behavior and brain structure. Nevertheless, the idea that personal activity shapes the brain is implicit in strategies for healthy cognitive aging as well as in the idea that individuality is reflected in the brain's connectome. We have shown that even isogenic mice kept in a shared enriched environment (ENR) developed divergent and stable social and exploratory trajectories. As these trajectories—measured as roaming entropy (RE)—positively correlated with adult hippocampal neurogenesis, we hypothesized that a feedback between behavioral activity and adult hippocampal neurogenesis might be a causal factor in brain individualization. We used cyclin D2 knockout mice with constitutively extremely low levels of adult hippocampal neurogenesis and their wild‐type littermates. We housed them for 3 months in a novel ENR paradigm, consisting of 70 connected cages equipped with radio frequency identification antennae for longitudinal tracking. Cognitive performance was evaluated in the Morris Water Maze task (MWM). With immunohistochemistry we confirmed that adult neurogenesis correlated with RE in both genotypes and that D2 knockout mice had the expected impaired performance in the reversal phase of the MWM. But whereas the wild‐type animals developed stable exploratory trajectories with increasing variance, correlating with adult neurogenesis, this individualizing phenotype was absent in D2 knockout mice. Here the behaviors started out more random and revealed less habituation and low variance. Together, these findings suggest that adult neurogenesis contributes to experience‐dependent brain individualization.

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Section: Discussionmentioning

confidence: 99%

Loss of individualized behavioral trajectories in adult neurogenesis‐deficient cyclin D2 knockout mice

et al. 2023

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“…NSCs are traditionally divided into mitotically quiescent B1-type cells and highly proliferative B2-type cells, giving rise to, among others, GRPs. The latter are generated before activation, which is driven by distinct cues including neurodegeneration, thus maintaining the molecular balance between differentiation and self-renewal [ 11 , 33 , 79 , 125 , 155 ].…”

Section: Sources Of Grpsmentioning

confidence: 99%

Glial-restricted progenitor cells: a cure for diseased brain?

Rogujski,

Lukomska,

Janowski

et al. 2024

Biol Res

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The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.

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“…CCND2 is the only D-type cyclin expressed in the adult hippocampus [70], with Ccnd2 knockout mice (Ccnd2-KO) displaying reduced hippocampal neuron production [71]. However, these Ccnd2-KO-associated brain abnormalities result in limited impact on behavioural phenotypes [72].…”

Section: Cyclin D2mentioning

confidence: 99%

D-Type Cyclins in Development and Disease

Saleban,

Harris,

Poulter

2023

Genes

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D-type cyclins encode G1/S cell cycle checkpoint proteins, which play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterized by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarize and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

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Impaired Generation of Transit-Amplifying Progenitors in the Adult Subventricular Zone of Cyclin D2 Knockout Mice

Cited by 6 publications

References 58 publications

Loss of individualized behavioral trajectories in adult neurogenesis‐deficient cyclin D2 knockout mice

Loss of individualized behavioral trajectories in adult neurogenesis‐deficient cyclin D2 knockout mice

Glial-restricted progenitor cells: a cure for diseased brain?

D-Type Cyclins in Development and Disease

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