Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice DOI Open Access
Yevheniia Ishchenko,

Amanda T. Jeng,

Shufang Feng

и другие.

Опубликована: Дек. 20, 2024

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 RhoG; GEF2: RhoA) that control neuronal development connectivity. It remains unclear how discrete differentially impact these events. Here, we investigate heterozygosity for NDD-associated Trio – +/K1431M (ASD), +/K1918X +/M2145T (bipolar disorder, BPD) mouse behavior, brain development, synapse structure function. Heterozygosity different impacts motor, social, cognitive behaviors distinct ways align clinical phenotypes humans. head size corresponding changes dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although was only modestly altered the variant heterozygotes, observe significant synaptic function plasticity. We also identified glutamate release cortico-cortical synapses. The K1431M GEF1 domain has impaired ability promote GTP on Rac1, but mice exhibit increased activity, levels GEF Tiam1. Acute inhibition NSC23766 rescued deficits cortex. Our work reveals yield overlapping mice, demonstrates an essential role presynaptic release, underscores importance studying vivo.

Язык: Английский

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction DOI
Eva A. Kuznetsova,

Guzalia F. Zakirjanova,

Andrei N. Tsentsevitsky

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2025, Номер 477(3), С. 421 - 439

Опубликована: Янв. 9, 2025

Язык: Английский

Процитировано

2
Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice DOI Open Access
Yevheniia Ishchenko,

Amanda T. Jeng,

Shufang Feng

и другие.

Опубликована: Май 7, 2025

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 RhoG; GEF2: RhoA) that control neuronal development connectivity. It remains unclear how discrete differentially impact these events. Here, we investigate heterozygosity for NDD-associated Trio – +/K1431M (ASD), +/K1918X +/M2145T (bipolar disorder, BPD) mouse behavior, brain development, synapse structure function. Heterozygosity different impacts motor, social, cognitive behaviors distinct ways model clinical phenotypes humans. head size, corresponding changes dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although was only modestly altered the variant heterozygotes, observe significant synaptic function plasticity. We also identified glutamate release cortico-cortical synapses. The K1431M GEF1 domain has impaired ability promote GTP on Rac1, but mice exhibit increased activity, levels GEF Tiam1. Acute inhibition NSC23766 rescued deficits cortex. Our work reveals yield overlapping mice, demonstrates an essential role presynaptic release, underscores importance studying vivo.

Язык: Английский

Процитировано

0
Heterozygosity for neurodevelopmental disorder-associatedTRIOvariants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice DOI Creative Commons
Yevheniia Ishchenko,

Amanda T. Jeng,

Shufang Feng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 6, 2024

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 RhoG; GEF2: RhoA) that control neuronal development connectivity. It remains unclear how discrete differentially impact these events. Here, we investigate heterozygosity for NDD-associated Trio - +/K1431M (ASD), +/K1918X +/M2145T (bipolar disorder, BPD) mouse behavior, brain development, synapse structure function. Heterozygosity different impacts motor, social, cognitive behaviors distinct ways model clinical phenotypes humans. head size, corresponding changes dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although was only modestly altered the variant heterozygotes, observe significant synaptic function plasticity. We also identified glutamate release cortico-cortical synapses. The K1431M GEF1 domain has impaired ability promote GTP on Rac1, but mice exhibit increased activity, levels GEF Tiam1. Acute inhibition NSC23766 rescued deficits cortex. Our work reveals yield overlapping mice, demonstrates an essential role presynaptic release, underscores importance studying vivo.

Язык: Английский

Процитировано

1
The synaptic vesicle cluster as a controller of pre‐ and postsynaptic structure and function DOI Creative Commons
Sofiia Reshetniak, Cristian A. Bogaciu, Stefan Bonn

и другие.

The Journal of Physiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

Abstract The synaptic vesicle cluster (SVC) is an essential component of chemical synapses, which provides neurotransmitter‐loaded vesicles during activity, at the same time as also controlling local concentrations numerous exo‐ and endocytosis cofactors. In addition, SVC hosts molecules that participate in other aspects function, from cytoskeletal components to adhesion proteins, affects location function organelles such mitochondria endoplasmic reticulum. We argue here these features extend functional involvement synapse formation, signalling plasticity, well stabilization metabolism. propose changes size coalesce with postsynaptic compartment, supporting interplay between pre‐ dynamics. Thereby, could be seen ‘all‐in‐one’ regulator structure should investigated more detail, reveal molecular mechanisms control heterogeneity. image

Язык: Английский

Процитировано

1
Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice DOI Open Access
Yevheniia Ishchenko,

Amanda T. Jeng,

Shufang Feng

и другие.

Опубликована: Дек. 20, 2024

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 RhoG; GEF2: RhoA) that control neuronal development connectivity. It remains unclear how discrete differentially impact these events. Here, we investigate heterozygosity for NDD-associated Trio – +/K1431M (ASD), +/K1918X +/M2145T (bipolar disorder, BPD) mouse behavior, brain development, synapse structure function. Heterozygosity different impacts motor, social, cognitive behaviors distinct ways align clinical phenotypes humans. head size corresponding changes dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although was only modestly altered the variant heterozygotes, observe significant synaptic function plasticity. We also identified glutamate release cortico-cortical synapses. The K1431M GEF1 domain has impaired ability promote GTP on Rac1, but mice exhibit increased activity, levels GEF Tiam1. Acute inhibition NSC23766 rescued deficits cortex. Our work reveals yield overlapping mice, demonstrates an essential role presynaptic release, underscores importance studying vivo.

Язык: Английский

Процитировано

1
Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice DOI Open Access
Yevheniia Ishchenko,

Amanda T. Jeng,

Shufang Feng

и другие.

Опубликована: Дек. 20, 2024

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 RhoG; GEF2: RhoA) that control neuronal development connectivity. It remains unclear how discrete differentially impact these events. Here, we investigate heterozygosity for NDD-associated Trio – +/K1431M (ASD), +/K1918X +/M2145T (bipolar disorder, BPD) mouse behavior, brain development, synapse structure function. Heterozygosity different impacts motor, social, cognitive behaviors distinct ways align clinical phenotypes humans. head size corresponding changes dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although was only modestly altered the variant heterozygotes, observe significant synaptic function plasticity. We also identified glutamate release cortico-cortical synapses. The K1431M GEF1 domain has impaired ability promote GTP on Rac1, but mice exhibit increased activity, levels GEF Tiam1. Acute inhibition NSC23766 rescued deficits cortex. Our work reveals yield overlapping mice, demonstrates an essential role presynaptic release, underscores importance studying vivo.

Язык: Английский

Процитировано

0