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Abnormal hippocampal neurogenesis in Parkinson’s disease: relevance to a new therapeutic target for depression with Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder characterized by motor dysfunction, including bradykinesia, tremor, rigidity, and postural instability. Recent clinical findings recognize PD as a complex disease with diverse neuropsychiatric complications. Depression is the most frequent non-motor psychiatric symptom experienced in PD, and it is associated with poor quality of life. While the pathophysiology of PD-associated depression is not directly related to neurodegenerative processes in the substantia nigra, underlying mechanisms remain unclear and there are few symptomatic treatments. Altered adult hippocampal neurogenesis is considered crucial for the development and treatment of depression. In genetic animal models and human postmortem studies of PD, severely impaired adult neurogenesis has been observed, with patients showing hippocampal atrophy and disrupted hippocampal neurogenesis. Because adult newborn neurons appear to exert various functions, which relate to non-motor symptoms observed in PD, there might be a close correlation between malformation of newborn neurons in the adult hippocampus and depressive symptoms. Here, we discuss current concepts regarding impaired hippocampal neurogenesis and non-motor symptoms of PD, and review PD-associated pathophysiological factors regulating neurogenesis, including inflammatory signaling and autophagy. We present a novel framework for targeting adult hippocampal neurogenesis, which could provide a promising treatment for PD-associated depression.

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Acknowledgements

This work was supported by the GRRC program of Gyeonggi province (#GRRC-CHA2017-A02, Validity and Safety Evaluation of Regional Specialized Resources) and the Grants #2015R1D1A1A01059598, #2015M3A9E1028326, #2016R1C1B1011117 and #2016M3A9E8941671 from the Ministry of Science, ICT & Future Planning through the National Research Foundation of Korea.

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  1. College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea

    Juhee Lim, Yeojin Bang & Hyun Jin Choi

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  1. Juhee Lim
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Correspondence to Hyun Jin Choi.

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Lim, J., Bang, Y. & Choi, H.J. Abnormal hippocampal neurogenesis in Parkinson’s disease: relevance to a new therapeutic target for depression with Parkinson’s disease. Arch. Pharm. Res. 41, 943–954 (2018). https://doi.org/10.1007/s12272-018-1063-x

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