Restrained Dendritic Growth of Adult-Born Granule Cells Innervated by Transplanted Fetal GABAergic Interneurons in Mice with Temporal Lobe Epilepsy

Gupta, Jyoti; Bromwich, Mark; Radell, Jake E.; Arshad, Muhammad Nauman; Gonzalez, Selena; Luikart, Bryan W.; Aaron, Gloster B.; Naegele, Janice R.

doi:10.1523/eneuro.0110-18.2019

Cited by 14 publications

(10 citation statements)

References 83 publications

(113 reference statements)

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“…Parvalbumin-positive interneurons associated in close proximity with the adult-born GCs (Gupta et al, 2019), form immature synaptic inputs onto proliferating newborn progeny and promote newborn neuronal progeny survival and development in the adult DG (Song et al, 2013), while suppressed PV-interneuron activity decreases the survival and maturation of newborn neurons (Song et al, 2013). In the present study, PV neurons were also spotted very close to NSCs.…”

Section: Discussionsupporting

confidence: 56%

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Song

2020

Front. Cell Dev. Biol.

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Physical exercise can alleviate some of the schizophrenia symptoms in patients, the mechanisms, however, are still unclear. To investigate whether the GABAergic interneuron involved in the therapeutic effect of treadmill running on schizophrenia, the parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus (DG) was specifically activated or abolished and the effects were evaluated. In the MK801induced schizophrenia-like animal model, we found:(1) Treadmill running rescued the schizophrenia-related behavioral phenotypes, promoted the adult hippocampal neurogenesis, and increased the dendrite number and complexity of newborn neurons. (2) Treadmill running increased the number of PV-positive interneurons in the DG; genetic ablation of these interneurons reduced adult neurogenesis and abolished the effect of treadmill running on the schizophrenia-related behaviors. Consistently, chemogenetic activation of these interneurons improved neurogenesis and alleviated the schizophrenia-related behaviors. These results suggest a pivotal role of PV-positive interneuron-mediated adult neurogenesis in exercise. (3) However, schizophreniarelated behavioral phenotypes and adult neurogenesis in the DG could still be reversed by exercise after specifically knocking out the schizophrenia-related gene ErbB4 in PV interneurons, as a means to reduce their GABA release. These results suggest that activation of PV interneurons in the DG is sufficient for treadmill running to reverse schizophrenia-like phenotypes.

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Section: Discussionsupporting

confidence: 56%

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Song

2020

Front. Cell Dev. Biol.

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“…Moreover, endogenous populations of hippocampal GABAergic interneurons promote survival of dentate GCs (Dieni et al, 2013), while endogenous subsets of PV-expressing hippocampal GABAergic interneurons specifically enhance survival of adult-born GCs (Song et al, 2013). We previously found that E13.5 MGE-derived transplants consist of approximately 37% PV+ GABAergic interneurons; many of the transplanted cells distribute throughout the molecular and GCL layers, where upon maturation, they form extensive inhibitory synaptic contacts to the dendrites of adult-born GCs (Hunt et al, 2013; Henderson et al, 2014; Gupta et al, 2019). Therefore, the transplanted cells may be responsible for increasing PV+ synaptic contacts with adult-born GCs, contributing to their survival and integration into synaptic networks.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, patch-clamp electrophysiological recordings in brain slices from mice with TLE showed increased spontaneous inhibitory postsynaptic currents in granule cells in slices with transplants (Henderson et al, 2014). The transplanted cells form extensive synaptic contacts associated with post-synaptic gephyrin puncta in the host brains and optogenetic stimulation of the transplanted cells induces strong inhibitory postsynaptic currents (Henderson et al, 2014; Gupta et al, 2019; Arshad et al, 2021). Despite mounting evidence that enhancing inhibitory synaptic transmission in the hippocampus or reducing adult neurogenesis are effective approaches for reducing seizures in rodent models of TLE, little is known about the underlying mechanisms for these therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Transplants of Fetal GABAergic Progenitors Regulate Adult Neurogenesis in Mice with Temporal Lobe Epilepsy

Arshad

Oppenheimer

Jeong

et al. 2022

Preprint

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GABAergic interneurons within the dentate gyrus of the hippocampus regulate adult neurogenesis, including proliferation, migration, and maturation of new granule cells born in the subgranular zone (SGZ) of the dentate gyrus (DG). In temporal lobe epilepsy (TLE), some adult-born granule cells migrate ectopically into the hilus, and these cells contribute to increased hyperexcitability and seizures. Yet, transplanting embryonic day 13.5 fetal mouse medial ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of mice with TLE ameliorates spontaneous seizures, due in part, to increased postsynaptic inhibition of adult-born granule cells. Here, we asked whether MGE progenitor transplantation affects earlier stages of adult neurogenesis, by comparing patterns of neurogenesis in naive mice and epileptic (TLE) mice, with or without MGE transplants. In naive and TLE mice, transplanted MGE cells showed comparable migration and process outgrowth. However, in TLE mice with MGE transplants, fewer adult-born Type 3 progenitors migrated ectopically. Furthermore, more Type 3 progenitors survived and migrated into the granule cell layer (GCL), as determined by immunostaining for doublecortin or the thymidine analogue, bromodeoxyuridine (BrdU). To determine whether MGE transplants affected earlier stages of adult neurogenesis, we compared proliferation in the SGZ two-hours after pulse labeling with BrdU in naive vs. TLE mice and found no significant differences. Furthermore, MGE progenitor transplantation had no effect on cell proliferation in the SGZ. Moreover, when compared to naive mice, TLE mice showed increases in inverted Type 1 progenitors and Type 2 progenitors, concomitant with a decrease in the normally oriented radial Type 1 progenitors. Strikingly, these alterations were abrogated by MGE transplantation. Thus, MGE transplants appear to reverse seizure-induced abnormalities in adult neurogenesis by increasing differentiation and radial migration of adult-born granule cell progenitors, outcomes that may ameliorate seizures.

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“…Therefore, freshly obtained MGE cells may be more suitable for transplantation. Another possible structural mechanism for the anti-epileptic effect of MGE cells is increased GABAergic innervation by transplanted MGE progenitor cells, which may limit dendritic growth in adult hippocampal dentate granule cells ( Gupta et al, 2019 , Table 1 ). MGE progenitor cells from E13.5 GFP mice were transplanted into the hippocampus of mice 2 months after SE ( Casalia et al, 2017 , Table 1 ).…”

Section: Potential Of Medial Ganglionic Eminence Cell Transplantation...mentioning

confidence: 99%

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

Han

2022

Front. Cell. Neurosci.

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Excitatory projection neurons and inhibitory interneurons primarily accomplish the neural activity of the cerebral cortex, and an imbalance of excitatory-inhibitory neural networks may lead to neuropsychiatric diseases. Gamma-aminobutyric acid (GABA)ergic interneurons mediate inhibition, and the embryonic medial ganglionic eminence (MGE) is a source of GABAergic interneurons. After transplantation, MGE cells migrate to different brain regions, differentiate into multiple subtypes of GABAergic interneurons, integrate into host neural circuits, enhance synaptic inhibition, and have tremendous application value in diseases associated with interneuron disorders. In the current review, we describe the fate of MGE cells derived into specific interneurons and the related diseases caused by interneuron loss or dysfunction and explore the potential of MGE cell transplantation as a cell-based therapy for a variety of interneuron disorder-related diseases, such as epilepsy, schizophrenia, autism spectrum disorder, and Alzheimer’s disease.

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Restrained Dendritic Growth of Adult-Born Granule Cells Innervated by Transplanted Fetal GABAergic Interneurons in Mice with Temporal Lobe Epilepsy

Abstract: Visual Abstract

Cited by 14 publications

References 83 publications

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Hippocampal Transplants of Fetal GABAergic Progenitors Regulate Adult Neurogenesis in Mice with Temporal Lobe Epilepsy

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

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