Abstract
Numerous studies have demonstrated that neurological disorders such as epilepsy, autism, schizophrenia, and others are caused by dysfunctions in the neuronal network. A properly balanced interplay between inhibitory and excitatory neurons is crucial for optimal neuronal network functioning. Inhibitory neurons migrate from their birthplace in the developing brain to reach their final destinations. Disruptions in this balance can for example arise from delayed migration, erroneous migration, and other factors, often associated with neurological disorders. This research focuses on investigating the effects of prenatal DNA damage, induced by X-rays, on the development and migration of inhibitory neurons.
In this study, the mouse model is used to compare the effects of prenatal DNA damage induced by X-rays with normal conditions. Both irradiated and non-irradiated (sham) mice are evaluated at various time points during development to track the migration of inhibitory neurons across different stages. Nkx2.1 reporter mice were employed, wherein interneurons were genetically manipulated to express GFP. This genetic modification enabled the tracking of interneurons born in the medial ganglionic eminence (MGE) during their migration process. By utilizing various immunohistochemical staining techniques, a comparison was made between irradiated and non-irradiated brains. Prior to conducting the analyses, optimization of the staining protocol was performed to obtain the best possible results. Based on the specific staining utilized, several analyses were carried out to evaluate the number of interneurons in different migration streams or cortical layers.
The findings of this research reveal that prenatal DNA damage induced by X-rays diminishes the development of inhibitory neurons. Additionally, a negative effect on the migration of interneurons in various migration streams (MZ, SP, and SVZ) was observed. Despite differences in the migration of inhibitory neurons following prenatal radiation, there is no disparity in the number of inhibitory neurons reaching their final destinations. These results suggest that a potential imbalance caused by prenatal DNA damage induced by X-rays is not linked to a reduction in the number of inhibitory neurons reaching their final destinations. However, defects have been identified during the migration from their birthplace to their final destinations. Further research is necessary to understand how these defects can contribute to an imbalance. Since not only the number but also the proper functioning of inhibitory neurons contributes to the excitation-inhibition balance, further investigation into their functionality is required. This will contribute to a better understanding of how prenatal DNA damage can lead to an imbalance in excitatory and inhibitory neurons.
In this study, the mouse model is used to compare the effects of prenatal DNA damage induced by X-rays with normal conditions. Both irradiated and non-irradiated (sham) mice are evaluated at various time points during development to track the migration of inhibitory neurons across different stages. Nkx2.1 reporter mice were employed, wherein interneurons were genetically manipulated to express GFP. This genetic modification enabled the tracking of interneurons born in the medial ganglionic eminence (MGE) during their migration process. By utilizing various immunohistochemical staining techniques, a comparison was made between irradiated and non-irradiated brains. Prior to conducting the analyses, optimization of the staining protocol was performed to obtain the best possible results. Based on the specific staining utilized, several analyses were carried out to evaluate the number of interneurons in different migration streams or cortical layers.
The findings of this research reveal that prenatal DNA damage induced by X-rays diminishes the development of inhibitory neurons. Additionally, a negative effect on the migration of interneurons in various migration streams (MZ, SP, and SVZ) was observed. Despite differences in the migration of inhibitory neurons following prenatal radiation, there is no disparity in the number of inhibitory neurons reaching their final destinations. These results suggest that a potential imbalance caused by prenatal DNA damage induced by X-rays is not linked to a reduction in the number of inhibitory neurons reaching their final destinations. However, defects have been identified during the migration from their birthplace to their final destinations. Further research is necessary to understand how these defects can contribute to an imbalance. Since not only the number but also the proper functioning of inhibitory neurons contributes to the excitation-inhibition balance, further investigation into their functionality is required. This will contribute to a better understanding of how prenatal DNA damage can lead to an imbalance in excitatory and inhibitory neurons.
Original language | Dutch |
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Qualification | Other |
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Date of Award | 5 Jun 2023 |
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State | Published - 5 Jun 2023 |