| Cellular and Molecular Neurosciences Section |
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| Neuroendocrine and Neuroimmune Mechanisms |
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| Studies of presenilin-1 (PS-1) mutant knockin mice have provided evidence for an important contribution of altered immune function to the pathogenesis of Alzheimer's disease. Investigators in the Cellular and Molecular Neuroscience Unit have shown that lymphocytes in the spleen show abnormalities in responses to various stimuli in presenilin-1 mutant mice. This Figure shows immunostaining of spleens of wild-type and PS-1 mutant mice with an antibody that recognizes activated caspase-3, a marker of apoptosis. There is enhanced apoptosis of lymphocytes in spleens of the PS-1 mutant mice. Such immune alterations are consistent with studies of Alzheimer's patients and suggest a contribution of altered immune function to the disease process. |
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| Alzheimer's disease patients often exhibit altered responses to stress including anxiety and depression. Studies by LNS investigators in the Cellular and Molecular Neuroscience Unit have shown that transgenic mice expressing a mutant form of amyloid precursor protein, linked to familial Alzheimer's disease, exhibit abnormal responses to various types of stress. Specifically, the mice show abnormal regulation of the hypothalamic - pituitary - adrenal axis under stress conditions and the inability to properly regulate blood glucose levels. These mice exhibit amyloid deposits in their brains. This Figure shows in situ hybridization analyses of mRNAs encoding corticotrophin releasing hormone (CHR; left), mineralocorticoid receptors (middle) and glucocorticoid receptors (right) in coronal brain sections from an APP mutant mouse. Together with additional data, these studies show that levels of CRH are increased in neurites of neurons associated with amyloid deposits. These kinds of alterations may contribute to the aberrant stress responses in this mouse model of Alzheimer's disease. |
