Chronic dietary α-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice

Quinn, Joseph F.; Bussiere, Joseph R.; Hammond, Rebecca; Montine, Thomas J.; Henson, Edward; Jones, Richard E.; Stackman, Robert W.

doi:10.1016/j.neurobiolaging.2005.12.014

Cited by 146 publications

(83 citation statements)

References 88 publications

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“…Other studies have shown that ET alone or LA alone was sufficient to enhance spatial learning and memory and growth factors in transgenic mice and human AD patients (16,37). These findings were confirmed by the results of this study, which demonstrated that it was possible to elicit positive spatial learning and memory changes and increase BDNF protein levels in APPsw Tg mice with ET or LA alone.…”

Section: Discussionsupporting

confidence: 90%

“…Conversely, ET reduces amyloid-ß plaques and improves cognitive function, synaptic plasticity, and neurogenesis in AD Tg mice (13,44). Furthermore, LA ameliorates cognitive dysfunction and reduces Aß-induced oxidative damage in the brains of AD Tg mice (37,42). However, the exact mechanisms that regulate the effects of ET and LA either individually or in COMA on AD-related apoptosis are still unclear.…”

Section: Discussionmentioning

confidence: 99%

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The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Cho¹

2010

Int J Mol Med

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Abstract. Exercise training was suggested as a practical therapeutic strategy for human subjects suffering from Alzheimer's disease (AD) in our previous study. Therefore, the purpose of this study was to investigate the effects of combining exercise training with the administration of antioxidants on the pathological phenotype of AD. To accomplish this, non-transgenic mice (Non-Tg) and NSE/ APPsw Tg mice were treated with ·-lipoic acid and treadmill exercised for 16 weeks, after which their brains were evaluated to determine whether any changes in the pathological phenotype-related factors occurred. The results indicated that (i) the combination-applied (COMA) Tg group with exercise training (ET) and ·-lipoic acid administration (LA) showed ameliorated spatial learning and memory compared to the sedentary (SED)-Tg and single-treatment groups; (ii) there were no differences in the level of Aß-42 peptides across groups; (iii) the level of glucose transporter-1 and brain-derived neurotrophic factor proteins were highly increased in the COMA group, (iv) ET and LA did not induce a synergistic effect on the expression of heat shock protein-70 and apoptotic proteins including Bax and caspase-3; (v) the levels of SOD-1 and CAT suppressing oxidative stress were extensively higher in the COMA than in the singletreated groups and (vi) there were no significant differences across groups regarding these serum characteristics, although these levels were lower than the SED-Tg group. Taken together, these results suggest that the combination with ET and LA may contribute to protect the neuron injury induced by Aß peptides and may be considered an effective therapeutic strategy for human subjects suffering from AD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Cho¹

2010

Int J Mol Med

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“…37 and 38). Moreover, antioxidants have been used as a therapeutic approach to treat AD (39,40), but have been only mildly effective, perhaps because they are not sufficiently robust or because of their nonspecific nature or incorrect timing of administration. Our studies show that a mitochondria-targeted antioxidant such as a SOD-2 mimetic could offer potentially better therapeutic outcomes in the treatment of AD.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Massaad

Washington

Pautler

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

197

143

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-␤ (A␤) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced A␤ plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of A␤1-40 and A␤1-42, but did significantly reduce the A␤1-42 to A␤1-40 ratio, thereby shifting the balance toward a less amyloidogenic A␤ composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.antioxidant ͉ dementia ͉ mitochondria ͉ oxidative stress ͉ reactive oxygen species

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“…A study examining serial brain, plasma, and urine F 2 -IsoPs by the "modified method" (see Section V for description of F 2 -IsoP methods) found elevation in all three at 8 months of age, before to the appearance of plaque pathology, with further marked increases at 12 and 18 months of age, correlating with the onset and progression of Aβ plaque accumulation [57]. However, other investigators comparing 14-20 month old Aβ plaquebearing Tg2576 mice with age-matched wild type (wt) mice have repeatedly found no increase in cerebral cortical F 2 -IsoPs ("original method") or F 4 -Neuroprostanes (NeuroPs) [58,59]. Moreover, massive acute cerebral oxidative damage from status epilepticus induced in rats by kainate exposure fails to result in elevated plasma or urine F 2 -IsoPs, seriously challenging the idea that these markers in peripheral biofluids reflect neurochemical changes in brain.…”

Section: Transgenic Micementioning

confidence: 99%

“…As with vitamin E, melatonin treatment of Tg2576 mice early in life attenuates Aβ deposition [82], but initiation after the age of plaque formation does not alter Aβ burden [83]. Yet another well tolerated antioxidant, α-lipoic acid, improves hippocampal-dependent memory in Tg2576 mice but has no effect on cerebral lipid peroxidation or Aβ plaque burden [59]. Similarly, pyrrolidine dithiocarbamate, a clinically tolerated metal chelator, potent antioxidant, and inhibitor of nuclear factor κB, improves spatial learning in APP-PS1 mice but has no effect on Aβ burden [84].…”

Section: Transgenic Micementioning

confidence: 99%

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

Sonnen¹,

Breitner²,

Lovell³

et al. 2008

Free Radical Biology and Medicine

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Chronic dietary α-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice

Cited by 146 publications

References 88 publications

The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

The combination of exercise training and α-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer's disease in NSE/APPsw-transgenic mice

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

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