{"id":583,"date":"2016-12-20T04:52:09","date_gmt":"2016-12-20T09:52:09","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=583"},"modified":"2016-12-20T04:57:52","modified_gmt":"2016-12-20T09:57:52","slug":"p7c3-attenuates-the-scopolamine-induced-memory-impairments-in-c57bl6j-mice","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/p7c3-attenuates-the-scopolamine-induced-memory-impairments-in-c57bl6j-mice\/","title":{"rendered":"P7C3 Attenuates the Scopolamine-Induced Memory Impairments in C57BL\/6J Mice"},"content":{"rendered":"

Alzheimer\u2019s disease <\/a>(AD), the most common type of\u00a0dementia is a progressive neurodegenerative disorder\u00a0characterized by a decline in cognitive function and\u00a0memory impairment. Characteristic neuropathological features of AD are accumulation of amyloid plaques,\u00a0formation of neurofibrillary tangles, induction of oxidative\u00a0stress and inflammatory responses, and disturbance in\u00a0neurotransmission. Particularly, the impairment of\u00a0memory and cognitive dysfunction in AD is associated\u00a0with cholinergic (acetylcholine-producing) hypofunction\u00a0by increasing the acetyl-cholinesterase <\/a>(AchE) activity. Conversely, the major treatment for AD is AchE inhibitors, which improve the levels of acetylcholine by\u00a0delaying its degradation at cholinergic synapses.\u00a0However, due to the limitation of current medications for\u00a0treating AD such as relatively low efficacy, severe adverse\u00a0effects for the long-term use, and in-effectiveness in the\u00a0late stage of AD, it is very necessary to develop novel\u00a0and safe anti-amnesic compounds with neuroprotective\u00a0properties. In this regard, one promising new candidate of\u00a0interest in this study is P7C3<\/a>.<\/p>\n

Previous studies have showed that learning and memory\u00a0is controlled by a lot of proteins and signaling pathways,\u00a0especially the BDNF signaling pathway. BDNF is a neurotrophic factor closely involved in memory consolidation,\u00a0and the dysfunction of BDNF disrupts the hippocampusdependent memory formation . CREB is a transcription factor coupled to the activation of BDNF,\u00a0and plays important roles in many developmentally regulated processes, such as cell survival, hippocampal neurogenesis and long-term memory.<\/p>\n

P7C3 is an identified proneurogenic and neuroprotective\u00a0aminopropyl carbazole. Pieper et al. reported that\u00a0the intraperitoneal injection of P7C3 could significantly\u00a0enhance the hippocampal neurogenesis at a dose of 20 mg\/kg, while hippocampal neurogenesis is closely correlated\u00a0with learning and memory. By now, this compound has already been demonstrated to treat several brain\u00a0disorders in animal models, including the Parkinson\u2019s\u00a0disease, amyotrophic lateral sclerosis and traumatic brain\u00a0injury. Here, the author\u00a0speculated that P7C3 may have\u00a0anti-amnesic effects and exhibit a preventive\/therapeutic\u00a0potential for treating AD.<\/p>\n

Scopolamine<\/a> is a muscarinic acetylcholine receptor<\/a>\u00a0(mAChR) antagonist which impairs learning acquisition\u00a0and short-term memory in rodents and humans.\u00a0The scopolamine-induced amnesia has been widely used to\u00a0generate experimental animal models for the screening of\u00a0anti-amnesic drugs. In this study, the author\u00a0have utilized the\u00a0scopolamine model to assess the anti-amnesic effects of\u00a0P7C3, and furthermore, the actions of P7C3 were extended\u00a0to the molecular levels by examining the expression of\u00a0brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus and cortex.<\/p>\n

In this study, the major findings of this study are as follows. First, P7C3 produces anti-amnesic effects in multiple animal models screening for anti-amnesic activity, including\u00a0the passive avoidance task, Y-maze test and Morris water\u00a0maze. Second, the anti-amnesic\u00a0effects of P7C3 require the\u00a0BDNF signaling pathway, since it could be prevented by\u00a0selective inhibition of BDNF system in the hippocampus\u00a0and cortex. Together, these data identify a novel function\u00a0of P7C3 suggesting it could be developed as a potential\u00a0treatment for AD.<\/p>\n

AD is the most common form of age-related neurodegenerative disorder that is characterized with an insidious\u00a0loss of memory, associated functional decline, and behavioral disturbances. Cholinergic deficit is a major feature that is associated with memory loss and cognitive\u00a0dysfunction in AD, and so it is well known that the\u00a0anti-cholinergic agent scopolamine-induced memory deficits are similar to those found in age-related senile central\u00a0nervous system dysfunction. Therefore, scopolamine\u00a0challenge could serve as a useful tool for selecting compounds with therapeutic potential for treating AD. The\u00a0compound, P7C3, was selected in our study by virtue of the\u00a0knowledge that it demonstrates robust proneurogenic\u00a0activity as neurogenesis is closely involved in learning and\u00a0memory, and this compound also has neuroprotective effects while AD is always accompanied with\u00a0neuronal loss. P7C3 is orally bioavailable,\u00a0endowed with a relatively long half life, capable of\u00a0crossing the blood brain barrier, and safely tolerated by\u00a0mice. Here, the author\u00a0investigated whether P7C3 has anti-AD potential in the scopolamine-induced memory impairment animal model, and conducted a series of behavior\u00a0tests. Firstly, in the passive avoidance test, scopolamine\u00a0treatment reduced the step-through latency, which was\u00a0effectively restored by intraperitoneal injection of P7C3.\u00a0Secondly, in the Y-maze test, the scopolamine-treated mice\u00a0showed decreased spontaneous alternation compared with\u00a0that of vehicle-treated mice, which was significantly\u00a0improved by P7C3 pretreatment. Lastly, in the Morris\u00a0water-maze task, the scopolamine-treated animals took\u00a0longer time to find the platform than those animals in the\u00a0control group, and P7C3? scopolamine-treated animals\u00a0easily found the location of the hidden platform. Collectively, these data strongly suggest that P7C3 could be a\u00a0novel anti-AD compound.<\/p>\n

related products:<\/h4>\n
<\/div>
<\/th><\/th><\/th><\/th><\/th><\/tr><\/thead>
CAS Number <\/td>Product Name <\/td>Molecular Formula <\/td>Molecular Weight <\/td>Description <\/td><\/tr>
51-34-3 <\/td>Scopolamine<\/a><\/td>C17H21NO4 <\/td>303.35 <\/td>Source from herbs of Atropa belladonna L. Scopolamine produces rapid and significant symptom improvement in patients with depression. It rapidly reduces symptoms in both treatment history groups, and demonstrates sustained improvement even in treatment resistant patients. <\/td><\/tr>
301353-96-8 <\/td>P7C3<\/a><\/td>C21H18Br2N2O <\/td>474.188 <\/td>P7C3 is neurogenic and protects new neurons against apoptosis. It protects newborn neurons in the dentate gyrus and stimulates the growth of new neurons. <\/td><\/tr><\/tbody><\/table><\/div>\n

Reference:<\/h4>\n

Bo Jiang \u2022 Lu Song,\u00a0\u2022 Chao Huang \u2022 Wei Zhang.\u00a0P7C3 Attenuates the Scopolamine-Induced Memory Impairments\u00a0in C57BL\/6J Mice<\/p>\n","protected":false},"excerpt":{"rendered":"

Alzheimer\u2019s disease (AD), the most common type of\u00a0dementia is a progressive neurodegenerative disorder\u00a0characterized by a decline in cognitive function and\u00a0memory impairment. Characteristic neuropathological features of AD are accumulation of amyloid […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[21],"tags":[225,371,372],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/583"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=583"}],"version-history":[{"count":3,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/583\/revisions"}],"predecessor-version":[{"id":586,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/583\/revisions\/586"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=583"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=583"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=583"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}