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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 406 - 415 (10page)
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Purpose: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as atherapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modalityhas not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells(pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed theirmechanisms of therapeutic action. Materials and Methods: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesionof cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injectionof pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequentimmunostaining analyses. Results: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesteraseactivity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferasedid not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglialcells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. Conclusion: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populationsand cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than directdifferentiation of injected pMSCs into cholinergic neurons.
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참고문헌 (40)
참고문헌 신청
Pappas BA / 2000 / Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients / Neurobiol Aging 21:11~17
Hall H / 2014 / Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease / Brain 137:2493~2508
Ricceri L / 2004 / Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats / Exp Neurol 189:162~172
Baxter MG / 1995 / Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats / Behav Neurosci 109:714~722
Gelfo F / 2013 / Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration / Neurochem Res 38:2114~2123
Hall H / 2014 / Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease / Brain 137:2493~2508
Ricceri L / 2004 / Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats / Exp Neurol 189:162~172
Baxter MG / 1995 / Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats / Behav Neurosci 109:714~722
Gelfo F / 2013 / Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration / Neurochem Res 38:2114~2123
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