Article

Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice

Molecular Neurology Unit, Center of Excellence on Aging (Ce.S.I.), University G. d'Annunzio, Chieti-Pescara, Italy.
PLoS ONE (Impact Factor: 3.53). 03/2011; 6(3):e17971. DOI: 10.1371/journal.pone.0017971
Source: PubMed

ABSTRACT The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties.
In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology.
We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits.
Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD.

2 Bookmarks
 · 
220 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms. Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures. CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1(+) activated microglia in the cortex of the APP/PS1 mice. Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.
    Neuropsychiatric Disease and Treatment 01/2015; 11:537-48. DOI:10.2147/NDT.S78025 · 2.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose-Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death, and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide that has robust neuroprotective activity against ischemic brain damage. Methods-We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Results-Autophagic pathways such as reduction of phosphorylated mammalian target of rapamycin (mTOR)/p70S6K and the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Conclusions-Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences.
    Stroke 06/2014; 45(8). DOI:10.1161/STROKEAHA.114.005183 · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the potential beneficial effects of dietary anserine and carnosine (CRC) supplementation on cognitive functioning and physical activity of the elderly. The fifty-six subjects (65 + ) were allocated to the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was used. Data were collected at the baseline and after 13-weeks of supplementation. In the follow up procedure fifty one subjects took part. Chicken meat extract (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was administered 2.5 g per day which allowed to rich the level of 1 g CRC in dipeptides supplement. The cognitive function, physical capacity, body measurements, blood pressure and heart rate were assessed. After supplementation BMI decreased significantly (p < 0,05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p < 0,05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p < 0,05) at the baseline and after follow up at the CRC group. The mean values of the STMS scores showed the significant (p < 0,04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.
    Archives of Gerontology and Geriatrics 09/2014; 59(2). DOI:10.1016/j.archger.2014.04.008 · 1.53 Impact Factor

Full-text (3 Sources)

Download
93 Downloads
Available from
May 27, 2014