Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain

Anam, Mohammad Badrul; Ahmad, Saboor; Kudo, Masaki; Istiaq, Arif; Felemban, Athary; Ito, Naofumi; Ohta, Kunimasa

doi:10.1111/dgd.12646

Cited by 4 publications

(9 citation statements)

References 41 publications

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“…Since TSK shows direct interaction with Wnt, BMP and Notch, it is necessary to consider a holistic approach while searching for the exact mechanism of TSK function (Ahmad et al, ). Recently, our group found a regulatory role of Akhirin (AKH), a von Willebrand factor A superfamily protein, for the proliferation and differentiation of the NSCs originating from both SVZ and DG—the two neurogenic niches of mouse brain (Abdulhaleem et al, ; Acharjee, Abdulhaleem, Riyadh, & Ohta, ; Ahsan, Ohta, Kuriyama, & Tanaka, ; Anam et al, ). Both TSK and AKH are secretory proteins and their expression at hippocampal regions during early postnatal stages closely resemble each other.…”

Section: Discussionmentioning

confidence: 99%

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

et al. 2020

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Secreted proteoglycan molecule Tsukushi (TSK) regulates various developmental processes, such as early body patterning and neural plate formation by interacting with major signaling pathways like Wnt, BMP, Notch etc. In central nervous system, TSK inhibits Wnt signaling to control chick retinal development. It also plays important roles for axon guidance and anterior commissure formation in mouse brain. In the present study, we investigated the role of TSK for the development and proper functioning of mouse hippocampus. We found that TSK expression is prominent at hippocampal regions of early postnatal mouse until postnatal day 15 and gradually declines at later stages. Hippocampal dimensions are affected in TSK knockout mice (TSK‐KO) as shown by reduced size of hippocampus and dentate gyrus (DG). Interestingly, neural stem cell (NSC) density at the neural niche of DG was higher in TSK‐KO compared with wild‐type. The ratio of proliferating NSCs as well as the rate of overall cell proliferation was also higher in TSK‐KO hippocampus. Our in vitro study also suggests an increased number of neural stem/progenitor cells residing in TSK‐KO hippocampus. Finally, we found that the terminal differentiation of NSCs in TSK‐KO was disturbed as the differentiation to neuronal cell lineage was increased while the percentages of astrocytes and oligodendrocytes were decreased. Overall, our study establishes the involvement of TSK in hippocampal development, NSC maintenance and terminal differentiation at perinatal stages.

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Section: Discussionmentioning

confidence: 99%

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

et al. 2020

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“…Although the underlying mechanisms have not been elucidated, it is apparent that neurogenic niches undergo changes associated with aging that may underlie neurogenic decline (Demars, Hollands, Zhao Kda, & Lazarov, 2013; Hamilton & Holscher, 2012; Parthsarathy & Holscher, 2013). Sex was not included as a covariate in the proliferation and neurogenesis studies, and males and females were analyzed together, as previously described in similar studies (Anam et al, 2020). In this sense, we cannot exclude that larger populations of males and females, could provide approaches that are more accurate, and provide higher statistical power to detect differences among groups.…”

Section: Discussionmentioning

confidence: 99%

Cell proliferation and neurogenesis alterations in Alzheimer’s disease and diabetes mellitus mixed murine models

Hierro-Bujalance

Marco

Ramos-Rodríguez

et al. 2020

Journal of Neurochemistry

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The classic neuropathological features of Alzheimer's disease (AD) are accompanied by other complications, including alterations in adult cell proliferation and neurogenesis. Moreover recent studies have shown that traditional markers of the neurogenic process, such as doublecortin (DCX), may also be expressed in CD8+ T cells and ionized calcium‐binding adaptor molecule 1 (Iba1+) microglia, in the close proximity to senile plaques, increasing the complexity of the condition. Altered glucose tolerance, observed in metabolic alteratioins, may accelerate the neurodegenerative process and interfere with normal adult cell proliferation and neurogenesis. To further explore the role of metabolic disease in AD, we analyzed cell proliferation and neurogenesis using 5’‐bromo‐2’‐deoxyuridine and DCX immunohistochemistry in three different mouse models of AD and metabolic alterations: APP/PS1xdb/db mice, APP/PS1 mice on a long‐term high‐fat diet, and APP/PS1 mice treated with streptozotozin. As reported previously, an overall reduction in cell proliferation and neurogenesis was observed after streptozotocin administration. In contrast, an increase in cell proliferation and neurogenesis was detected in neurogenic niches in 14‐ and 26‐week‐old APP/PS1xdb/db mice, accompanied by a slight increase in cortical cell proliferation. While a similar trend was observed in animals on a high‐fat diet, differences were not statistically significant. We observed very few DCX+/CD8+ cells and no DCX+/Iba1+ cells were observed in the close proximity to senile plaques in any of the groups. Interestingly, metabolic parameters such as body weight and glucose and insulin levels were identified as reliable predictors of cell proliferation and neurogenesis in APP/PS1xdb/db mice. Furthermore, metabolic parameters were also associated with altered Aβ levels in the cortex and hippocampus of APP/PS1xdb/db mice. Altogether, our data suggest that metabolic disease may also interfere with central complications in AD.

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“…In the hippocampal DG, AKH expression was observed in the entire hippocampal region immediately after birth, followed by a specific expression in the hippocampal CA2 region at P20 (Figure 1C,E). Thus, from the embryonic stage, AKH is expressed in the brain niche areas and disappears in tandem with the cessation of neurogenesis around P20 when brain formation is approximately complete; this observation suggests the involvement of AKH in neurogenesis and neuronal differentiation during early development but not in adult neurogenesis [20].…”

Section: Akh Is Exclusively Localized In Brain Neurogenic Nichesmentioning

confidence: 91%

“…We have previously reported extensive expression of AKH in the niches of the CNS. AKH is specifically expressed in the ciliary marginal zone of the retina [18], the middle and ventral central canal of the spinal cord [19], and the SVZ and the DG of the hippocampus in the mouse CNS [20]. As AKH exhibits heterophilic cell adhesion activity, which has been confirmed by cell aggregation analysis [18], it is supposed to function as an extracellular adhesion factor regulating these niches in the CNS.…”

Section: Introductionmentioning

confidence: 88%

“…Self-renewal and differentiation potential of NSCs are dynamically regulated by various niche-derived factors, which relay signals in an autocrine or paracrine manner together with transcription factors that respond to those signals. To investigate whether AKH is a niche factor, we compared the brain morphology using AKH-/and AKH+/+ mice and found that the ventricles of AKH-/mice were widely expanded when compared with those of AKH+/+ mice (Figure 2A,B) [20]. The hippocampal DG region was reduced in AKH-/mice when compared to that in AKH+/+ mice (Figure 2D,E) [20].…”

Section: Effects Of Akh Knockout On Neurogenesis and Neuronal Differentiation In The Brain Nsc Nichementioning

confidence: 99%

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Regulation of the Brain Neural Niche by Soluble Molecule Akhirin

Kudo

Ohta

2021

JDB

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In the central nervous system (CNS), which comprises the eyes, spinal cord, and brain, neural cells are produced by the repeated division of neural stem cells (NSCs) during the development of the CNS. Contrary to the notion that the CNS is relatively static with a limited cell turnover, cells with stem cell-like properties have been isolated from most neural tissues. The microenvironment, also known as the NSC niche, consists of NSCs/neural progenitor cells, other neurons, glial cells, and blood vessels; this niche is thought to regulate neurogenesis and the differentiation of NSCs into neurons and glia. Although it has been established that neurons, glia, and blood vessels interact with each other in a complex manner to generate neural tissues in the NSC niche, the underlying molecular mechanisms in the CNS niche are unclear. Herein, we would like to introduce the extracellular secreted protein, Akhirin (AKH; Akhi is the Bengali translation for eye). AKH is specifically expressed in the CNS niche—the ciliary body epithelium in the retina, the central canal of the spinal cord, the subventricular zone, and the subgranular zone of the dentate gyrus of the hippocampus—and is supposedly involved in NSC niche regulation. In this review, we discuss the role of AKH as a niche molecule during mouse brain formation.

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Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain

Cited by 4 publications

References 41 publications

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells

Cell proliferation and neurogenesis alterations in Alzheimer’s disease and diabetes mellitus mixed murine models

Regulation of the Brain Neural Niche by Soluble Molecule Akhirin

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