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| Principal Investigator | |
| Principal Investigator's Name: | Hai Nguyen Duc |
| Institution: | Sunchon National University |
| Department: | Department of Pharmacy |
| Country: | |
| Proposed Analysis: | Background Neurodegenerative diseases (NDs) affect millions of people. Alzheimer’s disease is the most common neurodegenerative diseases. An estimated 5.4 million (2016) Americans have AD [1]. The estimated total healthcare costs for the treatment of AD are estimated at $305, with the cost expected to increase to more than $1 trillion as the population ages [2]. Until now, the specific causes of these diseases remained unknown. In order to understand the complex range of actions that influence the etiology of a vast range of neurodegenerative diseases, the basic mechanisms responsible for degeneration must be elucidated [3]. Recent evidence shows that hormones influence the risks and developments of neurodegenerative diseases [4]. Prolactin is well known as one of the most adaptable hormones with its multiple functions, especially in neurogenesis [5]. PRL crosses the blood-brain barrier and has strong modulatory effects on local hypothalamic growth to pass many brain regions. Furthermore, many studies that showed PRL functions in the central nervous system (CNS) and neurodegeneration [3, 5-11]. Nevertheless, the mechanisms responsible for the actions of PRL in a wide range of neurodegenerative disorders have not been determined, and literature on the topic is often inconsistent [6]. For example, some studies have shown that PRL regulates neurogenesis, contributes to stress adaptation, and promotes neuroprotection, whereas others have shown that PRL inhibits neurogenesis and promotes depressive-like behaviors [5]. In AD, PRL level was reported to be elevated in AD patients and may cause negative effects on cognitive function in some clinical studies, while in other studies, PRL was shown to reduce the risk of AD via inhibition of tau phosphorylation and protects the hippocampus [12, 13]. Interestingly, the PRL level is affected by some neurodegenerative diseases’ therapies. Therefore, it is necessary to resolve the question about the association between PRL and AD. A study in adult virgin female Wistar rat showed that several genes (Adora2a, Car3, Chat, Drd2, Egr2, Hif3a, Notch, Penk, Tac1, Ttr, Sema3A, and Penk) induced by PRL are related to the regulations of brain functions and processes associated with axons, synaptic transmission, and microglial regulation [14], and the expressions of these genes had been previously shown to be altered in neuroinflammatory diseases and NDDs [15-23]. Of note, Adora2a is related to synaptic impairment in neurons, and high Adora2a expression is related to neurogenesis and hippocampal volume in AD [24, 25]. On the other hand, PRL also modulates genes of the extracellular matrix (Col1a1 Col1a2, Fmod, Ptgds, and Aldh1a2), which are induced by physical activity and have been reported to suppress hippocampal aging in a premature aging animal model of AD [26]. Microglia are known to be related to either neurodegenerative or neuroprotective depending on their state of activation [18]. Thus, PRL-induced genes associated with microglial functions might play important roles in hippocampal neuroimmunomodulation or prevent neuronal cell damage [27-30]. Remarkedly, PRLR is also present in primary cell cultures of hippocampal neurons [31]. Thus, it has been suggested PRL could play a significant role in the prevention of hippocampus aging and in modulating microglial function process during hippocampal development and in the adult brain [31]. PRL can enhance memory, cognition, and learning by several mechanisms. First, PRL regulates Drd2 gene expression [14], which has been related to hippocampus-dependent plasticity, and thus, to hippocampal memory and learning [32]. Second, PRL might favor neuronal survival under conditions of kainic acid-induced excitotoxicity by increasing the expression of vesicular glutamate transporter 1, which is associated with Glu transport in neurons and contributes to the survival and plasticity of hippocampal neurons [33]. Increasing evidence indicates PRL positively influences memory, cognition, and learning [34-37]. A previous study indicated that high and low levels of PRL are related to cognitive impairment in tasks involving processing speed and verbal recall in pregnant women [12], and in older men, higher PRL levels were related to poorer working memory and verbal ability [38]. A study on hippocampus-dependent memory in PRLR null mice reported learning and memory impairments in both sexes [37]. In a male rat hyperprolactinemia model object recognition was impaired with no modification of spatial learning [39], and in ovariectomized female rats, PRL prevented kainic acid-induced cognitive deficit in novel object recognition tests [40]. Furthermore, loss of PRL caused learning and memory deficits in PRL null mice, and these deficits were remedied by directly infusing recombinant PRL into hippocampus, which strongly suggested that PRL inadequacy in the adult mouse hippocampus related to impaired learning and memory [37]. This study is focusing on neuroendocrine in neurodegenerative diseases, especially, action of prolactin during neurodegeneration. Participants/population. Inclusion: studies with participants above 50 years and studies conducted around the world. Exclusion: studies with participants who are all younger than 50. Main outcome(s). 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| Additional Investigators |
