J Neurosci Res. 2006 May 18; [Epub ahead of print] Related Articles, Links
Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: Protective effects of R-alpha-lipoic acid.
Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, Packer L, Liu J.
Institute of Gerontology and Geriatrics, Chinese PLA General Hospital, Beijing, People's Republic of China.
Chronic systemic exposure of mice, rats, and Drosophila to D-galactose causes the acceleration of senescence and has been used as an aging model. The underlying mechanism is yet unclear. To investigate the mechanisms of neurodegeneration in this model, we studied cognitive function, hippocampal neuronal apoptosis and neurogenesis, and peripheral oxidative stress biomarkers, and also the protective effects of the antioxidant R-alpha-lipoic acid. Chronic systemic exposure of D-galactose (100 mg/kg, s.c., 7 weeks) to mice induced a spatial memory deficit, an increase in cell karyopyknosis, apoptosis and caspase-3 protein levels in hippocampal neurons, a decrease in the number of new neurons in the subgranular zone in the dentate gyrus, a reduction of migration of neural progenitor cells, and an increase in death of newly formed neurons in granular cell layer. The D-galactose exposure also induced an increase in peripheral oxidative stress, including an increase in malondialdehyde, a decrease in total anti-oxidative capabilities (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities. A concomitant treatment with lipoic acid ameliorated cognitive dysfunction and neurodegeneration in the hippocampus, and also reduced peripheral oxidative damage by decreasing malondialdehyde and increasing T-AOC and T-SOD, without an effect on GSH-Px. These findings suggest that chronic D-galactose exposure induces neurodegeneration by enhancing caspase-mediated apoptosis and inhibiting neurogenesis and neuron migration, as well as increasing oxidative damage. In addition, D-galactose-induced toxicity in mice is a useful model for studying the mechanisms of neurodegeneration and neuroprotective drugs and agents. © 2006 Wiley-Liss, Inc.
PMID: 16710848 [PubMed - as supplied by publisher]
Psychoneuroendocrinology. 2006 May 15; [Epub ahead of print] Related Articles, Links
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Effects of d-galactose on the expression of hippocampal peripheral-type benzodiazepine receptor and spatial memory performances in rats.
Chen CF, Lang SY, Zuo PP, Yang N, Wang XQ, Xia C.
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
The changes in spatial memory performances and the binding of hippocampal peripheral-type benzodiazepine receptor (PBR) induced by d-galactose (d-gal) were investigated in rats. The animals were randomly divided into two groups: saline-treated group and d-gal-induced aging group. All rats received 56 days of injection followed by 5 days of behavioral tests. The d-gal-induced aging rats presented significant impairment in water maze performance, compared with that in the saline-treated rats. A significant decrease in [(3)H]PK11195 binding in the synaptosomes from hippocampus in the d-gal-induced aging rats was observed, compared to that in the saline-treated rats. Meanwhile, the Scatchard analysis revealed that there was a decrease in B(max), with no significant change in K(D). Further analysis demonstrated that water maze performance was closely related to the PK11195 binding in all rats. These results suggest that d-gal decreased the density of PBR in hippocampal synaptosomes, which may be attributable to the progressive pathogenesis of aging in rats.
PMID: 16707226 [PubMed - as supplied by publisher]
Behav Brain Res. 2006 May 15; [Epub ahead of print] Related Articles, Links
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Quercetin reverses d-galactose induced neurotoxicity in mouse brain.
Lu J, Zheng YL, Luo L, Wu DM, Sun DX, Feng YJ.
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Xuzhou Normal University, Xuzhou 221116, China; Institute of Molecular Medicine and Genetics Research Center, School of Basic Medical Science, Southeast University, Nanjing 210009, China.
We assessed the neuroprotective effects of quercetin-feeding at doses of 5 and 10mg/(kgday) on Kunming mice injected daily with d-gal (50mg/(kgday)) by behavioral tests. Quercetin-fed mice showed higher activity upon induction by new environmental stimuli, lower anxiety and higher novelty-seeking behavior in the open field tasks, and significantly improved learning and memory ability in step-through and Morris water Maze tests compared with d-gal-treated mice. We further investigated the mechanisms involved in the neuroprotective effects of quercetin on mouse brain. Quercetin significantly increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level. These results imply that quercetin can reverse oxidant impairment induced by d-gal in mouse brain. Neurotoxicity is also associated with Ca(2+) overload induced by oxidant stress. Quercetin could maintain the Ca(2+) homeostasis in the brain of d-gal-treated mice. Furthermore, we also examined the expression of growth-associated protein GAP43 mRNA in mouse brain by in situ hybridization. We found that quercetin dramatically elevated the GAP43 mRNA expression in the brain of d-gal-treated mice to regenerate normal function of neurons against the cellular injury caused by d-gal.
PMID: 16707173 [PubMed - as supplied by publisher]
WTF is going on here? I've never heard so much as a peep about this before today. Please share your thoughts on the implications of this research and its relevance to humans -- specifically, whether daily ingestion of yogurt could produce negative effects in the brain.
On second thought, any dairy product containing lactose would pose the same problem, because if you are not lactose-intolerant, you will break down the lactose and absorb galactose in the small intestine.