Critical aspects of neurodevelopment

Chakraborty, Ranabir; Kumar, Manjeet; Clement, James P.

doi:10.1016/j.nlm.2021.107415

Cited by 10 publications

(4 citation statements)

References 376 publications

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“…Correspondingly, our data shows that KCC2 expression and function (EGABA) is mainly disrupted at P14-16. Thus, we chose this period as a critical period of development as most of our study involved the hippocampus (critical period ends at 3-week) (Chakraborty, Vijay Kumar, and Clement 2021). At P10-16, 6BIO treated Syngap1 +/mice showed partial correction of hyperactivity in the open field test (OFT) (total distance; behaviour at P80; Supplementary Figure 3A).…”

Section: Bio Prevents Behavioural Deficits Of Syngap1 +/Micementioning

confidence: 99%

Reversing GABA polarity corrects synaptic physiology and behavioural deficits in young adolescent Syngap1+/- mice

Verma

Kumar

Sharma

et al. 2021

Preprint

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Haploinsufficiency in SYNGAP1 is implicated in Intellectual Disability (ID) and Autism Spectrum disorder (ASD) and affects the maturation of dendritic spines. The abnormal spine development has been suggested to cause disbalance of excitatory and inhibitory (E/I) neurotransmission at distinct developmental periods. In addition, E/I imbalances in Syngap1+/- mice might be due to abnormalities in K+-Cl- co-transporter function (NKCC1, KCC2), in a similar manner as in the murine models of Fragile-X and Rett syndromes. To study whether an altered intracellular chloride ion concentration represents an underlying mechanism of altered function of GABAergic synapses in Dentate Gyrus Granule Cells of Syngap1+/- recordings were performed at different developmental stages of the mice. We observed that neurons at P14-15 of Syngap1+/- mice had depolarised membrane potential and a decreased Cl- reversal potential. The KCC2 expression was decreased compared to Wild-type (WT) mice at P14-15. Furtherly, the small molecule GSK-3β inhibitor, 6-bromoindirubin-3`-oxime (6BIO), was tested in an attempt to restore the function of GABAergic synapses. We discovered that intraperitoneal administration of 6BIO during the critical period or young adolescents normalized an altered E/I balance, the deficits of synaptic transmission, and behavioral performance like social novelty, anxiety, and memory of the Syngap1+/- mice. In summary, altered functionality of GABAergic synapses in Syngap1+/- mice is based on a reduced KCC2 expression and a subsequent increase in the intracellular chloride concentration that can be counteracted by the small molecule 6BIO. The 6BIO sufficiently restored cognitive, emotional, and social symptoms by pharmacological intervention, particularly, in adulthood.

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Section: Bio Prevents Behavioural Deficits Of Syngap1 +/Micementioning

confidence: 99%

Reversing GABA polarity corrects synaptic physiology and behavioural deficits in young adolescent Syngap1+/- mice

Verma

Kumar

Sharma

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…The critical period has been observed in various cortical regions, which contribute not only to sensory modalities but also to higher-order brain function. 3 , 4 Proper emergence of the critical period is important for the development of brain functions because mice that show abnormal critical period timing fail to develop proper neuronal functions. 5 , 6 In the visual system, studies have shown a causal relationship between critical period timing and functional maturation of GABAergic neural circuits.…”

Section: Introductionmentioning

confidence: 99%

Layer specific regulation of critical period timing and maturation of mouse visual cortex by endocannabinoids

Yoneda,

Kameyama,

Gotou

et al. 2024

iScience

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“…[3][4][5][6][7] In addition, dysfunction of normal plasticity during the critical period has been identified as a contributing factor in neurodevelopmental and neuropsychiatric disorders. [8][9][10] ASD is characterized by severe deficits of socialization, communication, and repetitive behaviors, 11 suggesting that alteration of the critical period contribute to these behaviors. 12 However, the development of fundamental treatments based on pathogenic mechanisms of disorders such as ASD has not yet been achieved, bringing an urgency to the research and development of such treatments.…”

Section: Introductionmentioning

confidence: 99%

Role of Immature Choroid Plexus in the Pathology of Autism Spectrum Disorder

Tanabe,

Saito,

Takasaki

et al. 2023

Preprint

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SUMMARYDuring gestation, the choroid plexus (ChP) produces protein-rich cerebrospinal fluid and matures prior to brain development. It is assumed that ChP dysfunction has a profound effect on developmental neuropsychiatric disorders, such as Autism Spectrum Disorder (ASD). However, the mechanisms linking immature ChP to the onset of ASD remain unclear. In this study, we found that ChP-specific CAMDI-knockout mice developed an immature ChP, alongside decreased multiciliogenesis and expression of differentiation marker genes following disruption of the cerebrospinal fluid barrier. These mice exhibited ASD-like behaviors, including impaired socialization with delayed critical period. Additionally, administration of Metformin, an FDA-approved drug, before the critical period achieved ChP maturation and restored social behaviors. Furthermore, ASD model mice and ASD patient-derived organoids developed immature ChP. These results indicate towards involvement of immature ChP in the pathogenesis of ASD and suggest the targeting of functional maturation of ChP as a therapeutic strategy for ASD.

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Critical aspects of neurodevelopment

Cited by 10 publications

References 376 publications

Reversing GABA polarity corrects synaptic physiology and behavioural deficits in young adolescent Syngap1+/- mice

Reversing GABA polarity corrects synaptic physiology and behavioural deficits in young adolescent Syngap1+/- mice

Layer specific regulation of critical period timing and maturation of mouse visual cortex by endocannabinoids

Role of Immature Choroid Plexus in the Pathology of Autism Spectrum Disorder

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