Association of impaired neuronal migration with cognitive deficits in extremely preterm infants

Kubo, Ken Ichiro; Deguchi, Kimiko; Nagai, Taku; Ito, Yukiko; Yoshida, Kouji; Endō, Toyoshige; Benner, Seico; Shan, Wei; Kitazawa, Ayako; Aramaki, Michihiko; Ishii, Kazuhiro; Shin, Minkyung; Matsunaga, Yuki; Kanehiro, Hiromichi; Kakeyama, Masaki; Tohyama, Chiharu; Tanaka, Kenji F.; Takashima, Sachio; Nakayama, Masahiro; Itoh, Masayuki; Hirata, Yukio; Antalffy, Barbara; Armstrong, Dawna; Yamada, Kiyofumi; Inoue, Ken; Nakajima, Kazunori

doi:10.1172/jci.insight.88609

Cited by 25 publications

(51 citation statements)

References 71 publications

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“…As a reference, we first performed Nissl staining of the mouse neocortex at P0 and confirmed that primitive clusters were present at the top of the CP (Figure a3, cyan arrowheads). Then, human neocortex at 23 GWs was Nissl stained (Figure b), and we observed densely accumulated cells that resembled the mouse PCZ at the outermost region of the human neocortical CP, as previously reported (Kubo et al, ). Highly magnified images showed that the cells at the outermost region of the CP were radially aligned with a high cell density, forming radial arrays of cells with a height of more than 10 cells and a width of one to two cells (Figure b3, cyan arrowheads), resembling the primitive neuronal clusters observed in the developing mouse and macaque neocortices, while the number of neurons that participated in one cluster was larger than that in mouse neocortex.…”

Section: Resultssupporting

confidence: 87%

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Shin

Kitazawa

Yoshinaga

et al. 2019

J of Comparative Neurology

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During development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. We previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the “primitive cortical zone (PCZ).” Here, we report that postmigratory immature neurons spend about 1–1.5 days in the PCZ. An electron microscopic analysis showed that the neurons in the PCZ tend to be in direct contact with each other, mostly in a radial direction, forming “primitive neuronal clusters” with a height of 3–7 cells and a width of 1–2 cells. A time‐course analysis of fluorescently labeled neurons revealed that the neurons took their positions within the primitive clusters in an inside‐out manner. The neurons initially participated in the superficial part of the clusters, gradually shifted their relative positions downward, and then left the clusters at the bottom of this structure. GABAergic inhibitory interneurons were also found within the primitive clusters in the developing mouse neocortex, suggesting that some clusters are composed of both excitatory neurons and inhibitory interneurons. Similar clusters were also observed in the outermost region of embryonic day (E) 78 cynomolgus monkey occipital cortex and 23 gestational week (GW) human neocortices. In the primate neocortices, including human, the presumptive primitive clusters seemed to expand in the radial direction more than that observed in mice, which might contribute to the functional integrity of the primate neocortex.

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Section: Resultssupporting

confidence: 87%

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Shin

Kitazawa

Yoshinaga

et al. 2019

J of Comparative Neurology

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“…69,70 We found that mouse embryonic ischemia delayed neuronal migration, altered neuronal alignment, and increased the number of ectopic neurons in the WM. 71 We started this study based on the finding that the densities/number of WM neurons was increased in extremely premature infants with brain ischemic injuries. 71 Extremely premature birth is known to be associated with an elevated risk of development of ASD or schizophrenia (the relative risk ratios are 9.7 and 4.5, respectively), 72,73 as well as the development of other disabilities.…”

Section: Migration Failure Of the Neocortical Neuronsmentioning

confidence: 99%

“…71 We started this study based on the finding that the densities/number of WM neurons was increased in extremely premature infants with brain ischemic injuries. 71 Extremely premature birth is known to be associated with an elevated risk of development of ASD or schizophrenia (the relative risk ratios are 9.7 and 4.5, respectively), 72,73 as well as the development of other disabilities. 74,75 Increase in the number/densities of WM neurons was also reported in a rat model of experimental maternal immune activation (MIA) produced by injection of PolyI:C. 76 Since MIA is also implicated as one of the environmental risk factors for the development of ASD and schizophrenia, 77 these results together suggest that the increased densities/number of WM neurons might be associated with the environmental risk factors for neuropsychiatric disorders.…”

Section: Migration Failure Of the Neocortical Neuronsmentioning

confidence: 99%

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

Kubo

2020

Psychiatry Clin Neurosci

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While neurons of the human cerebral cortex are mainly distributed in the gray matter, the white matter (WM) also contains some excitatory and inhibitory neurons, so‐called WM neurons. Studies on the cytoarchitectural alterations in the brains of patients with neuropsychiatric disorders have repeatedly reported increased densities of the WM neurons in a proportion of patients with schizophrenia and autism spectrum disorder. Although some studies have demonstrated increased densities of superficial WM neurons, others have demonstrated increased densities of deep WM neurons and increased WM neuron densities can be considered as one of the cross‐disease features of neuropsychiatric disorders. Nevertheless, what actually causes the increase in the densities of the WM neurons still remains under debate, and several hypothetical mechanisms have been proposed. The WM neurons in normal brains are considered as remnants of the subplate neurons, which represent a transient cytoarchitectural zone present during development of the mammalian neocortex; it has been suggested that increased densities of the WM neurons could result from inappropriate apoptosis of the subplate neurons in the brains of patients with neuropsychiatric disorders. On the other hand, recent experimental studies have demonstrated that genetic and environmental factors that enhance the risk of development of neuropsychiatric disorders could cause altered distribution of neurons in the WM. To understand the pathophysiology underlying the increased densities of the WM neurons, it is important to investigate the cellular characteristics of the WM neurons in the brains of both normal subjects and patients with neuropsychiatric disorders.

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“…Radial glial cells have been identified in extremely preterm infants (Kubo et al . ), and post‐mortem human brain studies have shown an emergence of neuroblasts around sites of injury in association with blood vessels (Jin et al . ).…”

Section: Enhancement Of Neuronal Migration and Perspectivesmentioning

confidence: 99%

“…In the neonatal human brain, neuroblasts migrate to the frontal lobe at least partly along blood vessels (Paredes et al 2016a). Radial glial cells have been identified in extremely preterm infants (Kubo et al 2017), and post-mortem human brain studies have shown an emergence of neuroblasts around sites of injury in association with blood vessels (Jin et al 2006). These observations suggest that neuroblast migration to lesioned sites along a scaffold may be evolutionarily conserved even in human brains.…”

Section: Enhancement Of Neuronal Migration and Perspectivesmentioning

confidence: 99%

Adult neurogenesis and its role in brain injury and psychiatric diseases

Hayashi

Jinnou

Sawamoto

et al. 2018

Journal of Neurochemistry

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In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles, and the subgranular zone of the hippocampus, which generate new neurons for the olfactory bulb and dentate gyrus, respectively. These adult NSCs retain their self-renewal ability and capacity to differentiate into neurons and glia as demonstrated by in vitro studies. However, their contribution to tissue repair in disease and injury is limited, lending credence to the claim by prominent neuropathologist Ramón y Cajal that 'once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably'. However, recent progress toward understanding the fundamental biology of adult NSCs and their role in pathological conditions has provided new insight into the potential therapeutic utility of endogenous NSCs. In this short review, we highlight two topics: the altered behavior of NSCs after brain damage and the dysfunction of NSCs and oligodendrocyte precursor cells, another type of undifferentiated cell in the adult brain, in mood affective disorders.

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Association of impaired neuronal migration with cognitive deficits in extremely preterm infants

Cited by 25 publications

References 71 publications

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

Adult neurogenesis and its role in brain injury and psychiatric diseases

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