Third Ventricular Injection of CCL2 in Rat Embryo Stimulates CCL2/CCR2 Neuroimmune System in Neuroepithelial Radial Glia Progenitor Cells: Relation to Sexually Dimorphic, Stimulatory Effects on Peptide Neurons in Lateral Hypothalamus

Chang, Guo‐Qing; Karatayev, Olga; Boorgu, Devi Sai Sri Kavya; Leibowitz, Sarah F.

doi:10.1016/j.neuroscience.2020.01.020

“…These new findings focus attention on the hypothalamic NEP as a site where neurons in the LH expressing CCL2 and CCR2 are born [11,12]. Together with in vitro studies [61,62] and our reports showing maternal CCL2 administration to increase CCL2 cell density in the NEP as shown here and in the LH [11,12] and central injection of CCL2 to stimulate CCL2 in radial glia cells and processes in embryonic NEP [63], they reveal an autoregulatory mechanism that involves an increase in the synthesis of CCL2 [63].…”

Section: Discussionsupporting

confidence: 73%

CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

Chang

¹

,

Karatayev

²

,

Boorgu

³

et al. 2020

J Neuroinflammation

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Background: Clinical and animal studies show that alcohol consumption during pregnancy produces lasting behavioral disturbances in offspring, including increased alcohol drinking, which are linked to inflammation in the brain and disturbances in neurochemical systems that promote these behaviors. These include the neuropeptide, melanin-concentrating hormone (MCH), which is mostly expressed in the lateral hypothalamus (LH). Maternal ethanol administration at low-to-moderate doses, while stimulating MCH neurons without affecting apoptosis or gliogenesis, increases in LH the density of neurons expressing the inflammatory chemokine CC motif ligand 2 (CCL2) and its receptor CCR2 and their colocalization with MCH. These neural effects associated with behavioral changes are reproduced by maternal CCL2 administration, reversed by a CCR2 antagonist, and consistently stronger in females than males. The present study investigates in the embryo the developmental origins of this CCL2/CCR2mediated stimulatory effect of maternal ethanol exposure on MCH neurons. Methods: Pregnant rats from embryonic day 10 (E10) to E15 during peak neurogenesis were orally administered ethanol at a moderate dose (2 g/kg/day) or peripherally injected with CCL2 or CCR2 antagonist to test this neuroimmune system's role in ethanol's actions. Using real-time quantitative PCR, immunofluorescence histochemistry, in situ hybridization, and confocal microscopy, we examined in embryos at E19 the CCL2/CCR2 system and MCH neurons in relation to radial glia progenitor cells in the hypothalamic neuroepithelium where neurons are born and radial glia processes projecting laterally through the medial hypothalamus that provide scaffolds for neuronal migration into LH.

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“…These new ndings focus attention on the hypothalamic NEP as a site where neurons in the LH expressing CCL2 and CCR2 are born [11,12]. Together with in vitro studies [62,63] and our reports showing maternal CCL2 administration to increase CCL2 cell density in the NEP as shown here and in the LH [11,12] and central injection of CCL2 to stimulate CCL2 in radial glia cells and processes in embryonic NEP [64], they reveal an auto-regulatory mechanism that involves an increase in synthesis of CCL2 [64].…”

Section: Discussionsupporting

confidence: 68%

CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: Involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

Chang

¹

,

Karatayev

²

,

Boo

³

et al. 2020

Preprint

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0

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Background: Clinical and animal studies show that alcohol consumption during pregnancy produces lasting behavioral disturbances in offspring, including increased alcohol drinking, which are linked to inflammation in the brain and disturbances in neurochemical systems that promote these behaviors. These include the neuropeptide, melanin-concentrating hormone (MCH), which is mostly expressed in the lateral hypothalamus (LH). Maternal ethanol administration at low-to-moderate doses, while stimulating MCH neurons without affecting apoptosis or gliogenesis, increases in LH the density of neurons expressing the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 and their colocalization with MCH. These neural effects associated with behavioral changes are reproduced by maternal CCL2 administration, reversed by a CCR2 antagonist, and consistently stronger in females than males. The present study investigates in the embryo the developmental origins of this CCL2/CCR2-mediated stimulatory effect of maternal ethanol exposure on MCH neurons.Methods: Pregnant rats from embryonic day 10 (E10) to E15 during peak neurogenesis were orally administered ethanol at a moderate dose (2 g/kg/day) or peripherally injected with CCL2 or CCR2 antagonist to test this neuroimmune system’s role in ethanol’s actions. Using real-time quantitative PCR, immunofluorescence histochemistry, in situ hybridization, and confocal microscopy, we examined in embryos at E19 the CCL2/CCR2 system and MCH neurons in relation to radial glia progenitor cells in the hypothalamic neuroepithelium where neurons are born and radial glia processes projecting laterally through the medial hypothalamus that provide scaffolds for neuronal migration into LH. Results: We demonstrate that maternal ethanol increases radial glia cell density and their processes while stimulating the CCL2/CCR2 system and these effects are mimicked by maternal administration of CCL2 and blocked by a CCR2 antagonist. While stimulating CCL2 colocalization with radial glia and neurons but not microglia, ethanol increases MCH neuronal number near radial glia cells and making contact along their processes projecting into LH. Further tests identify the CCL2/CCR2 system in NEP as a primary source of ethanol’s sexually dimorphic actions.Conclusions: These findings provide new evidence for how an inflammatory chemokine pathway functions within neuroprogenitor cells to mediate ethanol’s long-lasting, stimulatory effects on peptide neurons linked to adolescent drinking behavior.

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“…Research investigations focused on the radial glial-like astrocyte scaffold in the dentate gyrus of the hippocampus after various insults, including head trauma, have shown that these astrocytes hypertrophy and change their orientation [49][50][51][52][53][54][55][56]. The modification in astrocyte structure could serve as an anatomical substrate, offering chemotactic signals that contribute to the abnormal growth of epileptogenic circuits [57][58][59][60].…”

Section: Pathophysiology Of Post-traumatic Epilepsymentioning

confidence: 99%

Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview

Kazis,

Chatzikonstantinou,

Ciobica

et al. 2024

Biomedicines

1

0

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This paper presents an in-depth exploration of Post-Traumatic Epilepsy (PTE), a complex neurological disorder following traumatic brain injury (TBI), characterized by recurrent, unprovoked seizures. With TBI being a global health concern, understanding PTE is crucial for effective diagnosis, management, and prognosis. This study aims to provide a comprehensive overview of the epidemiology, risk factors, and emerging biomarkers of PTE, thereby informing clinical practice and guiding future research. The epidemiological aspect of the study reveals PTE as a significant contributor to acquired epilepsies, with varying incidence influenced by injury severity, age, and intracranial pathologies. The paper delves into the multifactorial nature of PTE risk factors, encompassing clinical, demographic, and genetic elements. Key insights include the association of injury severity, intracranial hemorrhages, and early seizures with increased PTE risk, and the roles of age, gender, and genetic predispositions. Advancements in neuroimaging, electroencephalography, and molecular biology are presented, highlighting their roles in identifying potential PTE biomarkers. These biomarkers, ranging from radiological signs to electroencephalography EEG patterns and molecular indicators, hold promise for enhancing PTE pathogenesis understanding, early diagnosis, and therapeutic guidance. The paper also discusses the critical roles of astrocytes and microglia in PTE, emphasizing the significance of neuroinflammation in PTE development. The insights from this review suggest potential therapeutic targets in neuroinflammation pathways. In conclusion, this paper synthesizes current knowledge in the field, emphasizing the need for continued research and a multidisciplinary approach to effectively manage PTE. Future research directions include longitudinal studies for a better understanding of TBI and PTE outcomes, and the development of targeted interventions based on individualized risk profiles. This research contributes significantly to the broader understanding of epilepsy and TBI.

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Third Ventricular Injection of CCL2 in Rat Embryo Stimulates CCL2/CCR2 Neuroimmune System in Neuroepithelial Radial Glia Progenitor Cells: Relation to Sexually Dimorphic, Stimulatory Effects on Peptide Neurons in Lateral Hypothalamus

Cited by 7 publications

References 71 publications

CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: Involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview

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