Alzheimer Disease: Tian M

Zhang X, Jin G, Wang L, Hu W, Tian M, Qin J, Huang H. · Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, PR China. · Hippocampus. · Pubmed #18831054 No free full text.

Abstract: Fimbria-fornix (FF), the septo-hippocampal pathway, was transected to model Alzheimer's disease (AD), which is characterized by loss of cholinergic afferent fibers in hippocampus. Various alternations may happen in the deafferented hippocampus. In this study, we determined the expression of Brn-4 in hippocampus after FF lesion. RT-PCR and Western blot showed that mRNA transcription and protein of Brn-4 increased significantly and reached to the peak at day 14 after FF lesion. Hybridization and immunohistochemistry indicated that Brn-4 signals in hippocampus and dentate gyrus (DG) of the deafferented side were significantly stronger than the normal side. More Brn-4 positive cells were identified in the DG of deafferented hippocampus. In the pyramidal and granular cells, Brn-4 positive cells were all NeuN positive neurons, whereas in the neurogenic area, subgranular zone (SGZ), only a part of Brn-4 positive cells were NeuN positive, and these Brn-4/NeuN double positive neurons in SGZ and hilus of DG increased significantly after the trauma induced by FF lesion. In vitro Brn-4 antibody attenuated the role of extract from deafferented hippocampus in promoting differentiation of hippocampal progenitors into MAP-2 positive neurons. This study demonstrated that after FF lesion, Brn-4 in the deafferented hippocampus was upregulated and might play an important role in inducing local progenitors to differentiate into neurons, which may compensate for the loss of cholinergic afferent fibers or other dysfunctions.

Zhang B, Dong Y, Zhang G, Moir RD, Xia W, Yue Y, Tian M, Culley DJ, Crosby G, Tanzi RE, Xie Z. · Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129-2060, USA. · J Biol Chem. · Pubmed #18326038 links to  free full text

Abstract: Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have been suggested to contribute to Alzheimer disease (AD) neuropathogenesis. Desflurane is one of the most commonly used inhalation anesthetics. However, the effects of desflurane on AD neuropathogenesis have not been previously determined. Here, we set out to assess the effects of desflurane and hypoxia on caspase activation, amyloid precursor protein (APP) processing, and amyloid beta-protein (Abeta) generation in H4 human neuroglioma cells (H4 naïve cells) as well as those overexpressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia (18% O(2)) alone affected caspase-3 activation, APP processing, and Abeta generation. However, treatment with a combination of 12% desflurane and hypoxia (18% O(2)) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP processing, and increased Abeta generation in H4-APP cells. Desflurane/hypoxia also increased levels of beta-site APP-cleaving enzyme in H4-APP cells. In addition, desflurane/hypoxia-induced Abeta generation could be reduced by the broad caspase inhibitor benzyloxycarbonyl-VAD. Finally, the Abeta aggregation inhibitor clioquinol and gamma-secretase inhibitor L-685,458 attenuated caspase-3 activation induced by desflurane/hypoxia. In summary, desflurane can induce Abeta production and caspase activation, but only in the presence of hypoxia. Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD.

Zhang X, Jin G, Tian M, Qin J, Huang Z. · Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China. · Neurosci Lett. · Pubmed #17300870 No free full text.

Abstract: The fate of neural stem/progenitor cells (NSCs/NPCs) in vivo lies on the local microenvironment. Whether the denervated hippocampus provides a stimulative role on the survival and differentiation of the anterior subventricular zone (SVZa) progenitors was investigated in the present study. In vivo the SVZa progenitors were transplanted into the denervated hippocampus and the contralateral side, and were found migrating along the subgranular layer. More implanted cells were found survived and differentiated into the Neurofilament 200 (NF-200) or beta-Tubulin-III positive neurons in the denervated than in the normal hippocampus at all points studied. In vitro the extracts from the denervated and normal hippocampus were used to induce differentiation of the SVZa progenitors. More progenitors incubated with the denervated hippocampal extract differentiated significantly into the MAP-2 or AChE positive neurons than those incubated with the normal hippocampal extract (P<0.05). We concluded that the deafferented hippocampus provided proper microenvironment for the survival and neuronal differentiation of neural progenitors.