Radix Puerariae modulates glutamatergic synaptic architecture and potentiates functional synaptic plasticity in primary hippocampal neurons

Bhuiyan, M.M.,Haque, Md.N.,Mohibbullah, Md.,Kim, Y.K.,Moon, I.S. Elsevier Ireland Ltd 2017 Journal of Ethnopharmacology Vol.209 No.-

Ethnopharmacological relevance: Neurologic disorders are frequently characterized by synaptic pathology, including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Therefore, to promote and/or protect synapses by the use of natural molecules capable of modulating neurodevelopmental events, such as, spinogenesis and synaptic plasticity, could offer a preventive and curative strategy for nervous disorders associated with synaptic pathology. Radix Puerariae, the root of Pueraria monatana var. lobata (Willd.) Sanjappa&Pradeep, is a Chinese ethnomedicine, traditionally used for the treatment of memory-related nervous disorders including Alzheimer's disease. In the previous study, we showed that the ethanolic extracts of Radix Puerariae (RPE) and its prime constituent, puerarin induced neuritogenesis and synapse formation in cultured hippocampal neurons, and thus could improve memory functions. Aims of the study: In the present study, we specifically investigated the abilities of RPE and puerarin to improve memory-related brain disorders through modulating synaptic maturation and functional potentiation. Materials and methods: Rat embryonic (E19) brain neurons were cultured in the absence or presence of RPE or puerarin. At predetermined times, cells were live-stained with DiO or fixed and immunostained to visualize neuronal morphologies, or lysed for protein harvesting. Morphometric analyses of dendritic spines and synaptogenesis were performed using Image J software. Functional pre- and postsynaptic plasticity was measured by FM1-43 staining and whole-cell patch clamping, respectively. RPE or puerarin-mediated changes in actin-related protein 2 were assessed by Western blotting. Neuronal survivals were measured using propidium iodide exclusion assay. Results: RPE and puerarin both: (1) promoted a significant increase in the numbers, and maturation, of dendritic spines; (2) modulated the formation of glutamatergic synapses; (3) potentiated synaptic transmission by increasing the sizes of reserve vesicle pools at presynaptic terminals; (4) enhanced NMDA receptor-mediated postsynaptic currents, and (5) increased cell viability against naturally occurring cell death. Moreover, upregulation of actin-related protein 2 (ARP2) in RPE and puerarin treated brain neurons suggest that RPE and puerarin induced synaptic plasticity might be associated, at least in part, with ARP2-mediated actin-dependent regulation of spinogenesis. Conclusions: Our findings indicate that RPE and puerarin might play a substantial role in the morphological and functional maturation of brain neurons and suggest that RPE and puerarin are potentially valuable preventative therapeutics for memory-related nervous disorders.

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

Park, Joo Min,Jung, Sung-Cherl,Eun, Su-Yong The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.6

At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity.

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

Joo Min Park,Sung-Cherl Jung,Su-Yong Eun 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.6

At central synapses, activity-dependent synaptic plasticity has a crucial role in information pro-cessing, storage, learning, and memory under both physiological and pathological conditions. One widely accepted model of learning mechanism and information processing in the brain is Hebbian Plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectively activity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid and synapse-specific processes. A number of recent studies have a strong focal point on the critical importance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slow and occur cell-widely. By putting them all together, this mini review defines an important conceptual difference between Hebbian and non-Hebbian plasticity.

Regulation of synaptic plasticity by Disheveled, a WNT signaling modulator.

Bo Hey Choi,Young Ha Kim,A-Young Kim,Young Ho Koh 한국응용곤충학회 2017 한국응용곤충학회 학술대회논문집 Vol.2017 No.04

Disheveled is a major regulator of WNT signalling pathway. It has been shown that WNT signaling is important for regulating synaptic plasticity. However, it is not still clear how Dsh is regulating synaptic plasticity. In this study, we used various methods to investigate how Dsh regulates synaptic plasticity. Our further studies will reveal unknown molecular and cellular mechanisms underlying WNT signaling dependent synaptic plasticity.

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization

박주민,정성철,은수용 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.6

At central synapses, activity-dependent synaptic plasticity has a crucial role in information processing,storage, learning, and memory under both physiological and pathological conditions. Onewidely accepted model of learning mechanism and information processing in the brain is HebbianPlasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD are respectivelyactivity-dependent enhancement and reduction in the efficacy of the synapses, which are rapid andsynapse-specific processes. A number of recent studies have a strong focal point on the criticalimportance of another distinct form of synaptic plasticity, non-Hebbian plasticity. Non-Hebbianplasticity dynamically adjusts synaptic strength to maintain stability. This process may be very slowand occur cell-widely. By putting them all together, this mini review defines an important conceptualdifference between Hebbian and non-Hebbian plasticity.

Effects of Swimming Exercise and Nicotine Injection during Pregnancy on Spatial Memory Function and Synaptic Plasticity Neurotrophic Factor in the Hippocampus of Rat Pups

백경아,윤진환,이희혁,김종오 한국생활환경학회 2016 한국생활환경학회지 Vol.23 No.4

In the present study, we attempted to determine the effects of maternal swimming exercise and nicotine injection during pregnancy on spatial learning memory ability and synaptic plasticity neurotrophic factor in hippocampal in rat offspring. After confirming pregnancy, the pregnant rats were divided into four groups (n = 6 in each group): the control group (CG), the swimming group (EG), the nicotine-treated group (NCG), and the swimming and nicotine-treated group (NEG). The experimental animals received 1mg nicotine/kg maternal body weight/day during gestation and lactation (G&L). Beginning on the 7 day of pregnancy, the pregnant rats in the swimming group were forced to swim on a pool for 30 min at a mild-intensity, once a day until delivery. After all the pregnant rats had given birth, there were rat pups available for use in this study in each group (n = 12 in each group). Here in this study, we have shown that both synaptic-plasticity neurotrophic factor expression and PSD were suppressed in nicotine-treated rats, whereas swimming exercise alleviated the nicotine-induced suppression of both synaptic-plasticity neurotrophic factor expression and PSD in the hippocampus of rats. The results of the present study indicate that swimming exercise may facilitate recovery from the CNS complications associated with smoking by inducing enhanced the morphological development of synapses in the hippocampus via the augmentation of synaptic-plasticity neurotrophic factor expression in the hippocampus.

Effects of Maternal Swimming Exercise and Nicotine Injection on Spatial Memory Function and Synaptic Plasticity in the Hippocampus of Rat Offspring

( Kyung-a Back ),( Jin-hwan Yoon ),( Hee-hyuk Lee ),( Jong-oh Kim ) 한국체육학회 2016 국제스포츠과학 학술대회 Vol.2016 No.1

Purpose: In the present study, we attempted to determine the effects of maternal swimming exercise and nicotine injection during pregnancy on spatial learning memory ability and synaptic plasticity neurotrophic factor in hippocampal in rat offspring. Method: After confirming pregnancy, the pregnant rats were divided into four groups(n = 6 in each group): the control group(CG), the swimming group(EG), the nicotine-treated group(NCG), and the swimming and nicotine-treated group(NEG). The experimental animals received 1mg nicotine/ kg maternal body weight/day during gestation and lactation (G&L). Beginning on the 7 day of pregnancy, the pregnant rats in the swimming group were forced to swim on a pool for 30 min at a mild-intensity, once a day until delivery. After all the pregnant rats had given birth, there were rat pups available for use in this study in each group(n = 12 in each group). Result: Here in this study, we have shown that both synaptic-plasticity neurotrophic factor expression and PSD were suppressed in nicotine-treated rats, whereas swimming exercise alleviated the nicotine-induced suppression of both synaptic-plasticity neurotrophic factor expression and PSD in the hippocampus of rats. Conclusion: The results of the present study indicate that swimming exercise may facilitate recovery from the CNS complications associated with smoking by inducing enhanced the morphological development of synapses in the hippocampus via the augmentation of synaptic-plasticity neurotrophic factor expression in the hippocampus.

Alterations in both acetylcholinesterase activity and synaptic scaffolding protein localization in the nervous system of Drosophila presenilin mutants

Won Tae Kim,Hee Jung Choi,Yunwoong Park,A-young Kim,김영호,서종복,이시혁,고영호 한국응용곤충학회 2010 Journal of Asia-Pacific Entomology Vol.13 No.4

Presenilins are one of two types of critical genetic factors in familial Alzheimer's disease, and they regulate various cellular functions such as intracellular Ca2+ homeostasis, the endoplasmic reticulum (ER) stress response, apoptosis, and synaptic transmission. We utilized Drosophila presenilin (psn) mutants as a model for studying the role of this gene in regulating acetylcholinesterase activity (AChE) and synaptic plasticity. Several lines of biochemical evidence indicated that AChE activity in a functionally null psn mutant (psnB3)was significantly reduced. In addition, we also found that psnB3 mutant neuromuscular junctions (NMJs) had smaller synaptic boutons and altered localization of Discs large, a synaptic scaffolding protein at the synaptic terminals compared to wild-type controls. These phenotypic defects were completely rescued in transgenic lines expressing the long form of wild-type Psn under an endogenous psn promoter cassette (PEPC-PsnWT;psnB3 lines). Taken together, these results indicate that Psn is important for regulating AChE activity, the size of synaptic boutons, and the localization of DLG at synaptic terminals.

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

Yang, Miyoung,Kim, Juhwan,Kim, Sung-Ho,Kim, Joong-Sun,Shin, Taekyun,Moon, Changjong Medknow PublicationsMedia Pvt Ltd 2012 Neural regeneration research Vol.7 No.21

<P>Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7–14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7–14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.</P>

Effects of Swimming Exercise and Nicotine Injection during Pregnancy on Spatial Memory Function and Synaptic Plasticity Neurotrophic Factor in the Hippocampus of Rat Pups

Kyung-A Back,Jin-Hwan Yoon,Hee-Hyuk Lee,Jong-Oh Kim 한국생활환경학회 2016 한국생활환경학회지 Vol.23 No.4

In the present study, we attempted to determine the effects of maternal swimming exercise and nicotine injection during pregnancy on spatial learning memory ability and synaptic plasticity neurotrophic factor in hippocampal in rat offspring. After confirming pregnancy, the pregnant rats were divided into four groups (n = 6 in each group): the control group (CG), the swimming group (EG), the nicotine-treated group (NCG), and the swimming and nicotine-treated group (NEG). The experimental animals received 1mg nicotine/㎏ maternal body weight/day during gestation and lactation (G&L). Beginning on the 7 day of pregnancy, the pregnant rats in the swimming group were forced to swim on a pool for 30 min at a mild-intensity, once a day until delivery. After all the pregnant rats had given birth, there were rat pups available for use in this study in each group (n = 12 in each group). Here in this study, we have shown that both synaptic-plasticity neurotrophic factor expression and PSD were suppressed in nicotine-treated rats, whereas swimming exercise alleviated the nicotine-induced suppression of both synaptic-plasticity neurotrophic factor expression and PSD in the hippocampus of rats. The results of the present study indicate that swimming exercise may facilitate recovery from the CNS complications associated with smoking by inducing enhanced the morphological development of synapses in the hippocampus via the augmentation of synaptic-plasticity neurotrophic factor expression in the hippocampus.