Ibotenic acid-induced lesions of the medial septum increase hippocampal membrane associated protein kinase c activity and reduce acetylcholine synthesis: prevention by a phosphatidylcholine/vitamin b12 diet11This work was supported by the Kiei-Kai Foundation.

Hung, Mei Chu; Shibasaki, Kazuo; Nishizono, Shoko; Sato, Masao; Ikeda, Ikuo; Masuda, Yasunobu; Kunou, Masaaki; Kawamura, Mitsuru; Yamashita, M.; Inoue, Setsuko; Imaizumi, Kazunori

doi:10.1016/s0955-2863(99)00088-1

Cited by 10 publications

(9 citation statements)

References 28 publications

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“…24,25 Thus, intracerebral injection of IBO served as a modeling method of AD, on the basis of its effects on cognitive and cholinergic changes. 16,26,27 In the present study, when determining the hippocampaldependent spatial memory with the Morris water maze test, there was a significant difference between sham rats and IBO rats, indicating that spatial memory was impaired in IBO rats. With regard to object memory, which is both hippocampus and cortex dependent, [28][29][30] there was also a significant difference between sham rats and IBO rats, suggesting that object memory was impaired in IBO rats.…”

Section: Discussionsupporting

confidence: 41%

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Hou

Zhang

Yang

et al. 2015

Rejuvenation Research

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This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.

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Section: Discussionsupporting

confidence: 41%

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Hou

Zhang

Yang

et al. 2015

Rejuvenation Research

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“…It is known that the nervous system can modulate circulating TNF- α levels via release of acetylcholine by the vagus nerve [109]. But our studies show that Cbl—essential for acetylcholine synthesis [110]—is the first known endogenous inhibitor of late HMGB1 mRNA expression. Both nicotine and ethyl-pyruvate have been used to block extracellular release of HMGB1 [109] but, in addition to the fact that HOCbl appears to impact on HMGB1 much further upstream, at least in tissues, neither drug is endowed with the safety profile of Cbl [111] and, more pertinently, neither is known to exert such a central, endogenous regulation of the immune response.…”

Section: Discussionmentioning

confidence: 89%

Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

Sampaio

Dalli

Brancaleone

et al. 2013

Mediators of Inflammation

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Background. NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation.

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“…The PC+vitamin B 12 diet contained 40 g/kg egg-yolk PC (PL-100LE, 89 : 2 % pure PC (% total fatty acids; palmitic acid 32 : 0, palmitoleic acid 1 : 4, stearic acid 13 : 2, oleic acid 29 : 8, linoleic acid 12 : 2, alinolenic acid 0 : 1, eicosamonoenoic acid 0 : 3, arachidonic acid 2 : 7, eicosapentaenoic acid 0 : 3, docosahexaenoic acid 6 : 1); Q.P., Tokyo, Japan) and 500 mg vitamin B 12 (Sigma, St Louis, MO, USA). The amounts of PC and vitamin B 12 used in the diet were based on findings from our previous experiment (Hung et al 2000). To balance the fatty acid composition and cholesterol content, the control diet was supplemented with (g/kg): 24 : 08 palm oil, 4 : 93 arachidonic acid-rich oil (Suntory, Kyoto, Japan), 0 : 29 docosahexaenoic acid (Maruha, Tokyo, Japan), 1 : 9 cholesterol (Nacalai Tesque, Kyoto, Japan).…”

Section: Animals and Dietmentioning

confidence: 99%

“…The PKC assay was carried out as described by Hung et al (2000). The hippocampus was homogenized with 5 vol.…”

Section: Assay Of Pkc Activitymentioning

confidence: 99%

“…Possible mechanisms may include alterations in acetylcholine synthesis and release, because basal forebrain cholinergic neurons participate in memory processes (Loy et al 1991), or they may be related to the function of choline-containing phospholipids in cell signalling events in the brain (Zeisel & Blusztajn, 1994). We reported that egg PC combined with vitamin B 12 ameliorates second messenger-mediated injury induced by ibotenic acid by modulating the activity of protein kinase C (PKC; Hung et al 2000).…”

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confidence: 99%

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Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine–vitamin B₁₂diet

et al. 2001

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Our objective was to determine whether dietary supplementation with phosphatidylcholine (PC) plus vitamin B 12 could afford beneficial effects on biochemical and biophysical events in the brain of senescence-accelerated mouse (SAM) substrain SAMP8. We measured learning behaviour, hippocampal protein kinase C (PKC) activity, cerebral antioxidant status, phospholipid composition and fatty acid composition in 6-month-old SAMP8 and in agematched controls (SAM substrain SAMR1). In comparison with SAMR1, SAMP8 showed a significant elevation in total grading score of senescence ðP , 0 : 05Þ and a significant decline in acquisition ðP , 0 : 05Þ: SAMP8 had a lower hippocampal PKC activity and cerebral PKC-b mRNA abundance than SAMR1. SAMP8 had increased cerebral lipid peroxide levels and proportion of sphingomyelin, and a lower proportion of 20 : 4n-6 and 22 : 6n-3 in cerebral phosphtidylethanolamine than SAMR1. SAMP8 fed the PC combined with vitamin B 12 diet had an increased PKC activity and a higher proportion of 22 : 6n-3 than SAMP8 fed the control diet. These results indicate the potential benefit of PC combined with vitamin B 12 as a dietary supplement.Phosphatidylcholine: Vitamin B 12 : Protein kinase C: Senescence-accelerated mouse: Brain

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Ibotenic acid-induced lesions of the medial septum increase hippocampal membrane associated protein kinase c activity and reduce acetylcholine synthesis: prevention by a phosphatidylcholine/vitamin b12 diet11This work was supported by the Kiei-Kai Foundation.

Cited by 10 publications

References 28 publications

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine–vitamin B₁₂diet

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Ibotenic acid-induced lesions of the medial septum increase hippocampal membrane associated protein kinase c activity and reduce acetylcholine synthesis: prevention by a phosphatidylcholine/vitamin b12 diet11This work was supported by the Kiei-Kai Foundation.

Cited by 10 publications

References 28 publications

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine–vitamin B12diet

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Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine–vitamin B₁₂diet