Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice
Purpose In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Korean Continence Society
2022-11-01
|
| Series: | International Neurourology Journal |
| Subjects: | |
| Online Access: | http://einj.org/upload/pdf/inj-2244254-127.pdf |
| _version_ | 1811213465210060800 |
|---|---|
| author | Sangjoon Lee Tae Kyoo Kim Ji Eun Choi Hye-Sun Kim Heh-In Im |
| author_facet | Sangjoon Lee Tae Kyoo Kim Ji Eun Choi Hye-Sun Kim Heh-In Im |
| author_sort | Sangjoon Lee |
| collection | DOAJ |
| description | Purpose In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored. Methods To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed. Results We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age. Conclusions This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD. |
| first_indexed | 2024-04-12T05:47:06Z |
| format | Article |
| id | doaj.art-1b5fe985660340bdacb038cb64b562dc |
| institution | Directory Open Access Journal |
| issn | 2093-4777 2093-6931 |
| language | English |
| last_indexed | 2024-04-12T05:47:06Z |
| publishDate | 2022-11-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj.art-1b5fe985660340bdacb038cb64b562dc2022-12-22T03:45:26ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312022-11-0126Suppl 2S10611610.5213/inj.2244254.1271020Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease MiceSangjoon Lee0Tae Kyoo Kim1Ji Eun Choi2Hye-Sun Kim3Heh-In Im4 Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, KoreaPurpose In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored. Methods To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed. Results We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age. Conclusions This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD.http://einj.org/upload/pdf/inj-2244254-127.pdfzbtb16alzheimer diseasecognitive dysfunctionsstriatumtranscription factors |
| spellingShingle | Sangjoon Lee Tae Kyoo Kim Ji Eun Choi Hye-Sun Kim Heh-In Im Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice International Neurourology Journal zbtb16 alzheimer disease cognitive dysfunctions striatum transcription factors |
| title | Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice |
| title_full | Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice |
| title_fullStr | Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice |
| title_full_unstemmed | Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice |
| title_short | Striatal ZBTB16 Is Associated With Cognitive Deficits in Alzheimer Disease Mice |
| title_sort | striatal zbtb16 is associated with cognitive deficits in alzheimer disease mice |
| topic | zbtb16 alzheimer disease cognitive dysfunctions striatum transcription factors |
| url | http://einj.org/upload/pdf/inj-2244254-127.pdf |
| work_keys_str_mv | AT sangjoonlee striatalzbtb16isassociatedwithcognitivedeficitsinalzheimerdiseasemice AT taekyookim striatalzbtb16isassociatedwithcognitivedeficitsinalzheimerdiseasemice AT jieunchoi striatalzbtb16isassociatedwithcognitivedeficitsinalzheimerdiseasemice AT hyesunkim striatalzbtb16isassociatedwithcognitivedeficitsinalzheimerdiseasemice AT hehinim striatalzbtb16isassociatedwithcognitivedeficitsinalzheimerdiseasemice |