Hyperhomocysteinaemia; with reference to its neuroradiological aspects

Berg, Marguerite van den; Knaap, Marjo S. van der; Boers, G.H.J.; Stehouwer, Coen D.A.; Rauwerda, J. A.; Valk, Jacob

doi:10.1007/s002340050119

Cited by 32 publications

(23 citation statements)

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“…Hcy is a sulfur-containing amino acid, and HHcy is one of the risk factors for Alzheimer's and neurodegenerative diseases [34][35][36]. For example, elevations of plasma Hcy are known to occur in Alzheimer's disease patients with cognitive and memory deficits [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

Kunisawa

Nakashima

Nagao

et al. 2015

Behavioural Brain Research

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Section: Discussionmentioning

confidence: 99%

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

Kunisawa

Nakashima

Nagao

et al. 2015

Behavioural Brain Research

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“…Evidence has accumulated that elevated plasma Hcy is a strong, independent risk factor of Alzheimer's disease (AD) (Clarke et al 1998;Dwyer et al 2004;Miller 1999;Seshadri et al 2002;Van Dam and Van Gool 2009). The deleterious influences of hyperhomocysteinemia have been known in neurological abnormalities, such as mental retardation, cerebral atrophy, and seizures (van den Berg et al 1995). However, the cellular and molecular mechanisms by which Hcy causes neurotoxicity are poorly understood.…”

Section: Introductionmentioning

confidence: 98%

Inhibition of Endogenous Hydrogen Sulfide Generation is Associated with Homocysteine-Induced Neurotoxicity: Role of ERK1/2 Activation

et al. 2010

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Both elevated homocysteine and decreased hydrogen sulfide (H(2)S) are observed in the brains of Alzheimer's disease (AD) patients. Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of homocysteine; however, H(2)S is an endogenous antioxidant gas. Therefore, the aim of this study was to investigate whether the imbalance of proportion to this endogenous protective antioxidant gas is involved in homocysteine-caused neurotoxicity. We show that homocysteine inhibits the generation of endogenous H(2)S and the expression and activity of cystathionine-β-synthetase (CBS), the main enzyme responsible for the generation of H(2)S in PC12 cells. S-Adenosylmethionine, an activator of CBS, not only prevents homocysteine-induced inhibition of endogenous H(2)S production but also attenuates homocysteine-triggered cytotoxicity and accumulation of ROS. We find that activation of ERK1/2 occurs in homocysteine-treated PC12 cells and blockade of ERK1/2 with U0126 abolished the homocysteine-induced cytotoxicity and inhibitory effect on endogenous H(2)S generation. These results indicate that homocysteine neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS and mediated by activation of ERK1/2. Our study suggests a promising future of H(2)S-based therapies for neurodegenerative diseases such as AD.

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“…Seizures are one of the major symptoms in hyperhomocysteinemia ( Van den Berg et al 1995), but it has been shown that classical antiepileptic drugs like phenytoin, fenobarbiton, carbamazepine and valproate increase plasma homocysteine level, thus showing the complexity of the relationship between homocysteine and epilepsy (Sener et al 2006). It has been suggested that homocysteine could be particularly harmful to all cells due to its metabolic conversion by methionyl-tRNA synthetases to highly reactive thioester homocysteine thiolactone (H) (Perla-Kajan et al 2007;Jakubowski 2004).…”

Section: Introductionmentioning

confidence: 99%

The Role of Nitric Oxide in Homocysteine Thiolactone-Induced Seizures in Adult Rats

et al. 2009

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The role of NO in epileptogenesis has been studied in different experimental models, and the reported results have been highly contradictory. The current study aimed to determine the role of NO in mechanisms of D: ,L: -homocysteine-thiolactone (H) induced seizures by testing the action of L: -arginine (NO precursor) and L: -NAME (NOS inhibitor) on behavioral and electroencephalographic (EEG) manifestations of H-induced seizures. The same holds true with the brain Na(+)/K(+)- and Mg(2+)-ATPase activity in adult male Wistar rats. We showed that the pretreatment with L: -arginine (300, 600 and 800 mg/kg, i.p.) in a dose-dependent manner significantly decreased lethality, seizure incidence and a number of seizure episodes and prolonged latency time to the first seizure elicited by a convulsive dose of H (8 mmol/kg, i.p.). L: -Arginine (800 mg/kg) completely reversed the inhibitory effect of H on the Na(+)/K(+)-ATPase activity in the hippocampus, the cortex and the brain stem and decreased the H-induced spike-and- wave discharges (SWD) formation in EEG. On the other hand, pretreatment with L: -NAME (200, 500 and 700 mg/kg, i.p.) potentiated a subconvulsive dose of H (5.5 mmol/kg, i.p) by increasing incidence and severity determined by a descriptive-rating scale (0-4) and shortening the latency time to the first seizure. The L: -NAME reversed H-induced alterations in the Na(+)/K(+)-ATPase activity in the cortex and the brain stem but not in the hippocampus. At last, the potentiated SWD appearance in EEG and an increased number of lethal outcomes occurred. In the present work, the modulation of NO levels, with the NO precursor and NOS inhibitor, was shed more light on its mechanism of action and answered the question whether NO could be included in the list of anticonvulsant agents in the D: ,L: -homocysteine thiolactone experimental model of seizures in adult rats.

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Hyperhomocysteinaemia; with reference to its neuroradiological aspects

Cited by 32 publications

References 0 publications

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

Inhibition of Endogenous Hydrogen Sulfide Generation is Associated with Homocysteine-Induced Neurotoxicity: Role of ERK1/2 Activation

The Role of Nitric Oxide in Homocysteine Thiolactone-Induced Seizures in Adult Rats

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