Hippocampal transplants of fetal GABAergic progenitors regulate adult neurogenesis in mice with temporal lobe epilepsy

Arshad, Muhammad Nauman; Oppenheimer, Simon; Jeong, Jaye; Buyukdemirtas, Bilge; Naegele, Janice R.

doi:10.1016/j.nbd.2022.105879

Cited by 11 publications

(5 citation statements)

References 120 publications

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“…Numerous studies have shown that glia cells can also originate from Nkx2.1-expressing precursor of embryonic MGE 56 and after migrating in the cortex, they transiently participate in cortical neurodevelopment to be later lost and replaced by other glia cell populations 57 . Furthermore, earlier studies showed the absence of proliferative markers following transplantation of embryonic MGE progenitors 22,58 and while unlikely, the presence of proliferating neural cells cannot be fully excluded. Future studies focused on additional markers and lineage analysis will be necessary to identify factor(s) driving astrocyte survival following transplantation into the DG microenvironment.…”

Section: Discussionmentioning

confidence: 91%

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Paterno,

Vu,

Hsieh

et al. 2024

Preprint

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Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. This strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating host brain environment influences on interneuron progenitors as they integrate is critical to optimizing this strategy across different disease states. Here, we systematically evaluated age and brain region influences on survival, migration and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to juvenile or adult. MGE progenitors migrate more widely in cortex compared to hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into dentate gyrus sub-region of early postnatal hippocampus can differentiate into astrocytes. Our results suggest that host brain environment critically regulates survival, spatial distribution and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.

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Section: Discussionmentioning

confidence: 91%

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Paterno,

Vu,

Hsieh

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…After migrating into the cortex, they transiently participate in cortical neurodevelopment before being replaced by other glia cell populations 57 . Furthermore, earlier studies showed the absence of proliferative markers following transplantation of embryonic MGE progenitors 22 , 58 . While unlikely, the presence of proliferating neural cells cannot be fully excluded.…”

Section: Discussionmentioning

confidence: 97%

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Paterno,

Vu,

Hsieh

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. The strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating how host brain environment influences the integration of interneuron progenitors is critical for optimizing this strategy across different disease states. Here, we systematically evaluated the influence of age and brain region on survival, migration, and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to transplantation during the juvenile or adult stages. MGE progenitors migrate more widely in the cortex compared to the hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into the dentate gyrus sub-region of the early postnatal hippocampus can differentiate into astrocytes. Our results suggest that the host brain environment critically regulates survival, spatial distribution, and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.

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“…Hilar ectopic DGCs form abnormal neural connections with adjacent DGCs and interfere with hippocampal neural circuits [49,63,64]. Although these cells have been mainly studied in temporal lobe epilepsy, which is characterized by recurrent seizures accompanied by temporarily increased hippocampal neurogenesis, they are also observed in patients with schizophrenia and alcoholism [65][66][67]. In traumatic brain injury, neurons formed after excessive stress such as trauma are localized ectopically to the hilus and molecular layer in the hippocampus [68,69].…”

Section: Discussionmentioning

confidence: 99%

Novel Psychopharmacological Herbs Relieve Behavioral Abnormalities and Hippocampal Dysfunctions in an Animal Model of Post-Traumatic Stress Disorder

Park,

Cai,

Yang

2023

Nutrients

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Post-traumatic stress disorder (PTSD) is an anxiety disorder caused by traumatic or frightening events, with intensified anxiety, fear memories, and cognitive impairment caused by a dysfunctional hippocampus. Owing to its complex phenotype, currently prescribed treatments for PTSD are limited. This study investigated the psychopharmacological effects of novel COMBINATION herbal medicines on the hippocampus of a PTSD murine model induced by combining single prolonged stress (SPS) and foot shock (FS). We designed a novel herbal formula extract (HFE) from Chaenomeles sinensis, Glycyrrhiza uralensis, and Atractylodes macrocephala. SPS+FS mice were administered HFE (500 and 1000 mg/kg) once daily for 14 days. The effects of HFE of HFE on the hippocampus were analyzed using behavioral tests, immunostaining, Golgi staining, and Western blotting. HFE alleviated anxiety-like behavior and fear response, improved short-term memory, and restored hippocampal dysfunction, including hippocampal neurogenesis alteration and aberrant migration and hyperactivation of dentate granule cells in SPS+FS mice. HFE increased phosphorylation of the Kv4.2 potassium channel, extracellular signal-regulated kinase, and cAMP response element-binding protein, which were reduced in the hippocampus of SPS+FS mice. Therefore, our study suggests HFE as a potential therapeutic drug for PTSD by improving behavioral impairment and hippocampal dysfunction and regulating Kv4.2 potassium channel-related pathways in the hippocampus.

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Hippocampal transplants of fetal GABAergic progenitors regulate adult neurogenesis in mice with temporal lobe epilepsy

Cited by 11 publications

References 120 publications

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Host brain environmental influences on transplanted medial ganglionic eminence progenitors

Novel Psychopharmacological Herbs Relieve Behavioral Abnormalities and Hippocampal Dysfunctions in an Animal Model of Post-Traumatic Stress Disorder

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