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

Kubo, Ken Ichiro

doi:10.1111/pcn.12962

Cited by 8 publications

(16 citation statements)

References 94 publications

(251 reference statements)

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“…PV-positive neurons were sparsely distributed in the cingulum and external capsule ( Figure 2D) and the densities of PV-positive neurons in WT and Het mice were similar in both areas (Figures 2E,F). Abnormalities in white matter neurons have been linked to mental disorders such as schizophrenia (Duchatel et al, 2016(Duchatel et al, , 2019Serati et al, 2019;Kubo, 2020), these results demonstrated, for the first time, an increased density of white matter neurons in a mouse model of schizophrenia.…”

Section: The Density Of White Matter Neuronsmentioning

confidence: 57%

“…In this study, we examined the cytoarchitecture of neurons in cortical layer VIb and the underlying white matter in heterozygous Disc1 mutant (Het) mice. If the abnormalities of these neurons found in this genetic mouse model of schizophrenia could replicate the findings in patients with schizophrenia (Duchatel et al, 2019;Serati et al, 2019;Kubo, 2020), then we may have a promising rodent model for investigating molecular and cellular events which might contribute to the pathogenesis of schizophrenia. Our results showed alterations in the density of layer VIb and white matter neurons as well as the morphology of layer VIb neurons in Disc1 mutant mice and suggested a pathogenic feature of neuropsychiatric disorders.…”

Section: Introductionmentioning

confidence: 71%

“…Increased interstitial white matter neurons have been associated with psychiatric disorders including schizophrenia and autism (Duchatel et al, 2019;Serati et al, 2019;Kubo, 2020). The pathogenic role of aberrant subplate neuron remnants had been suggested (Judaš et al, 2010;Kostović et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…A genetic study showed the expression profile of mouse subplate neurons associated with autism and schizophrenia . Abnormalities in subplate or white matter neurons have been linked to mental disorders such as schizophrenia (Duchatel et al, 2016(Duchatel et al, , 2019Serati et al, 2019;Kubo, 2020); however, the pathogenic role of remnant subplate neurons is still largely unknown (Judaš et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

2020

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Increased white matter neuron density has been associated with neuropsychiatric disorders including schizophrenia. However, the pathogenic features of these neurons are still largely unknown. Subplate neurons, the earliest generated neurons in the developing cortex have also been associated with schizophrenia and autism. The link between these neurons and mental disorders is also not well established. Since cortical layer VIb neurons are believed to be the remnant of subplate neurons in the adult rodent brain, in this study, we aimed to examine the cytoarchitecture of neurons in cortical layer VIb and the underlying white matter in heterozygous Disc1 mutant (Het) mice, a mouse model of schizophrenia. In the white matter, the number of NeuN-positive neurons was quite low in the external capsule; however, the density of these cells was found increased (54%) in Het mice compared with wildtype (WT) littermates. The density of PV-positive neurons was unchanged in the mutants. In the cortical layer VIb, the density of CTGF-positive neurons increased (21.5%) in Het mice, whereas the number of Cplx3-positive cells reduced (16.1%) in these mutants, compared with WT mice. Layer VIb neurons can be classified by their morphological characters. The morphology of Type I pyramidal neurons was comparable between genotypes while the dendritic length and complexity of Type II multipolar neurons were significantly reduced in Het mice. White matter neurons and layer VIb neurons receive synaptic inputs and modulate the process of sensory information and sleep/arousal pattern. Aberrances of these neurons in Disc1 mutants implies altered brain functions in these mice.

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Section: The Density Of White Matter Neuronsmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

2020

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“…41 It has been estimated that approximately 10-20% of the SP neurons survive and remain in the WM as the so-called WM neurons. 42,43…”

Section: Overview Of the Development Of The Neocortexmentioning

confidence: 99%

Human neocortical development as a basis to understand mechanisms underlying neurodevelopmental disabilities in extremely preterm infants

Kubo

Deguchi

2020

J of Obstet and Gynaecol

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Aim: Recent advances in perinatal and neonatal medicine have resulted in marked improvements in the survival rates of extremely preterm infants (born before 28 gestational weeks) around the world, and Japan is among the countries with the highest reported survival rates of extremely preterm infants. However, it remains a major concern that many survivors develop neurodevelopmental disabilities, including cognitive dysfunctions and neurodevelopmental disorders later in life. In order to understand the pathophysiological mechanisms underlying the neurodevelopmental disabilities observed in the survivors of extremely preterm births, we reviewed recently reported findings about the development of the human neocortex. Methods: First, we have summarized the current knowledge about the development of the neocortex, including recently reported human-and/or primate-specific developmental events. Next, we discussed the possible causal mechanisms underlying the development of neurodevelopmental disabilities in extremely preterm infants. Results: Around the birth of extremely preterm infants, neurogenesis and succeeding neuronal migrations are ongoing in the neocortex of human brain. Expansion and maturation of the subplate, which is thought to reflect the axonal wiring in the neocortex, is also prominent at this time. Conclusion: Brain injuries that occur around the birth of extremely preterm infants are presumed to affect the dynamic developmental events in the neocortex, such as neurogenesis, neuronal migrations and maturation of the subplate, which could underlie the neurodevelopmental disabilities that often develop subsequently in extremely preterm infants. These possibilities should be borne in mind while considering maternal and neonatal care to further improve the long-term outcomes of extremely preterm infants.

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The distribution, number, and certain neurochemical identities of infracortical white matter neurons in a chimpanzee (Pan troglodytes) brain

Swiegers

Bhagwandin

Williams

et al. 2021

J of Comparative Neurology

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We examined the number, distribution, and immunoreactivity of the infracortical white matter neuronal population, also termed white matter interstitial cells (WMICs), throughout the telencephalic white matter of an adult female chimpanzee. Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most numerous and dense close to the inner border of cortical layer VI, decreasing significantly in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed an estimate of approximately 137.2 million WMICs within the infracortical white matter of the chimpanzee brain studied. Immunostaining revealed subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS, approximately 14.4 million in number), calretinin (CR, approximately 16.7 million), very few WMICs containing parvalbumin (PV), and no calbindin-immunopositive neurons. The nNOS, CR, and PVimmunopositive WMICs, possibly all inhibitory neurons, represent approximately 22.6% of the total WMIC population. As the white matter is affected in many cognitive conditions, such as schizophrenia, autism, epilepsy, and also in neurodegenerative diseases, understanding these neurons across species is important for the translation of findings of neural dysfunction in animal models to humans. Furthermore, studies of WMICs in species such as apes provide a crucial phylogenetic context for understanding the evolution of these cell types in the human brain.

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

Cited by 8 publications

References 94 publications

Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

Human neocortical development as a basis to understand mechanisms underlying neurodevelopmental disabilities in extremely preterm infants

The distribution, number, and certain neurochemical identities of infracortical white matter neurons in a chimpanzee (Pan troglodytes) brain

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