Dataset Information

Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.

ABSTRACT: Parkinson's disease causes the most profound loss of the aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neuron (nDAN) subpopulation. The connectivity and functionality of ALDH1A1+ nDANs, however, remain poorly understood. Here, we show in rodent brains that ALDH1A1+ nDANs project predominantly to the rostral dorsal striatum, from which they also receive most monosynaptic inputs, indicating extensive reciprocal innervations with the striatal spiny projection neurons (SPNs). Functionally, genetic ablation of ALDH1A1+ nDANs causes severe impairments in motor skill learning, along with a reduction in high-speed walking. While dopamine replacement therapy accelerated walking speed, it failed to improve motor skill learning in ALDH1A1+ nDAN-ablated mice. Altogether, our study provides a comprehensive whole-brain connectivity map and reveals a key physiological function of ALDH1A1+ nDANs in motor skill acquisition, suggesting the motor learning processes require ALDH1A1+ nDANs to integrate diverse presynaptic inputs and supply dopamine with dynamic precision.

SUBMITTER: Wu J

PROVIDER: S-EPMC6741442 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.

Wu Junbing J Kung Justin J Dong Jie J Chang Lisa L Xie Chengsong C Habib Ahsan A Hawes Sarah S Yang Nannan N Chen Vivian V Liu Zhenhua Z Evans Rebekah R Liang Bo B Sun Lixin L Ding Jinhui J Yu Jia J Saez-Atienzar Sara S Tang Beisha B Khaliq Zayd Z Lin Da-Ting DT Le Weidong W Cai Huaibin H

Cell reports 20190701 5

Parkinson's disease causes the most profound loss of the aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neuron (nDAN) subpopulation. The connectivity and functionality of ALDH1A1+ nDANs, however, remain poorly understood. Here, we show in rodent brains that ALDH1A1+ nDANs project predominantly to the rostral dorsal striatum, from which they also receive most monosynaptic inputs, indicating extensive reciprocal innervations with the stri ...[more]

PMID: 31365862

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Project description:BACKGROUND: We showed there are specific ALDH1 autoantibodies in ovarian autoimmune disease and ovarian cancer, suggesting a role for ALDH1 in ovarian pathology. However, there is little information on the ovarian expression of ALDH1. Therefore, we compared ALDH1 expression in normal ovary and benign and malignant ovarian tumors to determine if ALDH1 expression is altered in ovarian cancer. Since there is also recent interest in ALDH1 as a cancer stem cell (CSC) marker, we assessed co-expression of ALDH1 with CSC markers in order to determine if ALDH1 is a potential CSC marker in ovarian cancer. METHODS: mRNA and protein expression were compared in normal human ovary and serous ovarian tumors using quantitative Reverse-Transcriptase PCR, Western blot (WB) and semi-quantitative immunohistochemistry (IHC). ALDH1 enzyme activity was confirmed in primary ovarian cells by flow cytometry (FC) using ALDEFLUOR assay. RESULTS: ALDH1 mRNA expression was significantly reduced (p < 0.01; n = 5) in malignant tumors compared to normal ovaries and benign tumors. The proportion of ALDH1+ cells was significantly lower in malignant tumors (17.1 ± 7.61%; n = 5) compared to normal ovaries (37.4 ± 5.4%; p < 0.01; n = 5) and benign tumors (31.03 ± 6.68%; p < 0.05; n = 5). ALDH1+ cells occurred in the stroma and surface epithelium in normal ovary and benign tumors, although surface epithelial expression varied more in benign tumors. Localization of ALDH1 was heterogeneous in malignant tumor cells and little ALDH1 expression occurred in poorly differentiated malignant tumors. In benign tumors the distribution of ALDH1 had features of both normal ovary and malignant tumors. ALDH1 protein expression assessed by IHC, WB and FC was positively correlated (p < 0.01). ALDH1 did not appear to be co-expressed with the CSC markers CD44, CD117 and CD133 by IHC. CONCLUSIONS: Total ALDH1 expression is significantly reduced in malignant ovarian tumors while it is relatively unchanged in benign tumors compared to normal ovary. Thus, ALDH1 expression in the ovary does not appear to be similar to breast, lung or colon cancer suggesting possible functional differences in these cancers. SIGNIFICANCE: These observations suggest that reduced ALDH1 expression is associated with malignant transformation in ovarian cancer and provides a basis for further study of the mechanism of ALDH1 in this process.

Dataset Information

Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.

Publications

Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.

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