Papers by Yuan-Shih Jennifer Hu
Experience of mice in a complex environment enhances neurogenesis and synaptic plasticity in the ... more Experience of mice in a complex environment enhances neurogenesis and synaptic plasticity in the hippocampus of wild type and transgenic mice harboring familial Alzheimer's disease (FAD)-linked APPswe/PS1ΔE9. In FAD mice, this experience also reduces levels of tau hyperphosphorylation and oligomeric β-amyloid. Although environmental enrichment has significant effects on brain plasticity and neuropathology, the molecular mechanisms underlying these effects are unknown. Here we show that environmental enrichment upregulates the Akt pathway, leading to the downregulation of glycogen synthase kinase 3β (GSK3β), in wild type but not FAD mice. Several neurotrophic signaling pathways are activated in the hippocampus of both wild type and FAD mice, including brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), and this increase is accompanied by the upregulation of the BDNF receptor, tyrosine kinase B (TrkB). Interestingly, neurotrophin-3 (NT-3) is upregulated in the brains of wild type mice but not FAD mice, while insulin growth factor-1 (IGF-1) is upregulated exclusively in the brains of FAD mice. Upregulation of neurotrophins is accompanied by the increase of N-Methyl-D-aspartic acid (NMDA) receptors in the hippocampus following environmental enrichment. Most importantly, we observed a significant increase in levels of cAMP response element- binding (CREB) transcripts in the hippocampus of wild type and FAD mice following environmental enrichment. However, CREB phosphorylation, a critical step for the initiation of learning and memory-required gene transcription, takes place in the hippocampus of wild type but not of FAD mice. These results suggest that experience of wild type mice in a complex environmental upregulates critical signaling that play a major role in learning and memory in the hippocampus. However, in FAD mice, some of these pathways are impaired and cannot be rescued by environmental enrichment.
… & Dementia: The …, Jan 1, 2010
No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site ...
Journal of …, Jan 1, 2010
Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA... more Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzhemier's disease (AD). We examined the effects of short-term (3 months) DHA enriched diet on plaque deposition and synaptic deficts in forebrain of young APPswe/PS1DE9 transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg mice consumed relatively more food daily than ntg female mice, independent of diet. Plaque load was significantly reduced in the cortex, ventral hippocampus and striatum of female APPswe/ PS1DE9 tg mice on DHA diet compared to female tg mice on control diet. Immunoblot quantitation of the APOE receptor, LR11, which is involved in APP trafficking and Ab production, were unchanged in mice on DHA or control diets. Moreover drebrin levels were significantly increased in the hippocampus of tg mice on the DHA diet. Finally, in vitro DHA treatment prevented amyloid toxicity in cell cultures. Our findings support the concept that increased DHA consumption may play and important role in reducing brain insults in female AD patients. V V C 2009 Wiley-Liss, Inc.
Journal of …, Jan 1, 2010
The FASEB Journal, Jan 1, 2010
Experience in complex environments induces numerous forms of brain plasticity, improving structur... more Experience in complex environments induces numerous forms of brain plasticity, improving structure and function. It has been long debated whether brain plasticity can be induced under neuropathological conditions, such as Alzheimer's disease (AD), to an extent that would reduce neuropathology, rescue brain structure, and restore its function. Here we show that experience in a complex environment rescues a significant impairment of hippocampal neurogenesis in transgenic mice harboring familial AD-linked mutant APPswe/ PS1⌬E9. Proliferation of hippocampal cells is enhanced significantly after enrichment, and these proliferating cells mature to become new neurons and glia. Enhanced neurogenesis was accompanied by a significant reduction in levels of hyperphosphorylated tau and oligomeric A, the precursors of AD hallmarks, in the hippocampus and cortex of enriched mice. Interestingly, enhanced expression of the neuronal anterograde motor kinesin-1 was observed, suggesting enhanced axonal transport in hippocampal and cortical neurons after enrichment. Examination of synaptic physiology revealed that environmental experience significantly enhanced hippocampal long-term potentiation, without notable alterations in basal synaptic transmission. This study suggests that environmental modulation can rescue the impaired phenotype of the Alzheimer's brain and that induction of brain plasticity may represent therapeutic and preventive avenues in AD.-Y.-S. Hu, P. Xu, G. Pigino, S. T. Brady, J. Larson, O. Lazarov. Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's diseaselinked APPswe/PS1⌬E9 mice. FASEB J. 24, 000 -000 (2010). www.fasebj.org Key Words: neural stem cells ⅐ oligomeric -amyloid ⅐ tau ⅐ long-term potentiation ⅐ axonal transport ⅐ kinesin
Uploads
Papers by Yuan-Shih Jennifer Hu