Journal of Alzheimer's disease : JAD
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Post-operative cognitive dysfunction (POCD) predominantly affects the elderly who suffer memory and concentration deficits after anesthesia and surgery. Animal studies have demonstrated anesthetic alone may contribute to POCD but results are variable and little is known about common anesthetics other than isoflurane. The present study investigated dose-dependence of desflurane anesthesia in young adult and aged rats. ⋯ Deficits were not long-lasting and were no longer present at 4 or 12 weeks. In contrast, young adult rats performed equally as well as sham-exposed control rats irrespective of desflurane dose. This study showed the effects of desflurane on learning and memory in the water maze are age and dose dependent and are brief in duration.
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Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. ⋯ Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble Aβ1-42 levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.
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We previously reported that activated microglia are involved in amyloid-β (Aβ) clearance and that stimulation of α7 nicotinic acetylcholine receptors (nAChR) in microglia enhances Aβ clearance. Nevertheless, how microglia and α7 nAChR in microglia are affected in Alzheimer's disease (AD) remains unknown. The present study aimed to collect fundamental data for considering whether microglia are potential targets for AD treatment and the appropriate timing of therapeutic intervention, by evaluating the temporal changes of Aβ, microglia, neurons, presynapses, and α7 nAChR by immunohistochemical studies in mouse models of AD. ⋯ In addition, α7 nAChR in microglia increased markedly at 6 months of age when activated microglia appeared for the first time, and decreased gradually coinciding with the increase of Aβ deposition. These findings suggest that early microglial activation is associated with α7 nAChR upregulation in microglia in APdE9 mice. These novel findings are important for the development of new therapeutic strategy for AD.
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Mitochondria are essential cytoplasmic organelles, critical for cell survival and death. Recent mitochondrial research revealed that mitochondrial dynamics-the balance of fission and fusion in normal mitochondrial dynamics--is an important cellular mechanism in eukaryotic cell and is involved in the maintenance of mitochondrial morphology, structure, number, distribution, and function. ⋯ Attempts have been made to develop molecules to reduce mitochondrial fission while maintaining normal mitochondrial fusion and function in those diseases that involve excessive mitochondrial fission. This review article discusses mechanisms of mitochondrial fission in normal and diseased states of mammalian cells and discusses research aimed at developing therapies, such as Mdivi, Dynasore and P110, to prevent or to inhibit excessive mitochondrial fission.
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Diffusion tensor imaging (DTI) allows the simultaneous measurement of several diffusion indices that provide complementary information on the substrate of white matter alterations in neurodegenerative diseases. These indices include fractional anisotropy (FA) as measure of fiber tract integrity, and the mode of anisotropy (Mode) reflecting differences in the shape of the diffusion tensor. We used a multivariate approach based on joint independent component analysis of FA and Mode in a large sample of 138 subjects with Alzheimer's disease (AD) dementia, 37 subjects with cerebrospinal fluid biomarker positive mild cognitive impairment (MCI-AD), and 153 healthy elderly controls from the European DTI Study on Dementia to comprehensively study alterations of microstructural white matter integrity in AD dementia and predementia AD. ⋯ Our findings suggest an early axonal degeneration in intracortical projecting fiber tracts in dementia and predementia stages of AD. An increase of Mode, parallel to an increase of FA, in the corticospinal tract suggests a more linear shape of diffusion due to loss of crossing fibers along relatively preserved cortico-petal and cortico-fugal fiber tracts in AD. Supporting this interpretation, we found three populations of fiber tracts, namely cortico-petal and cortico-fugal, commissural, and intrahemispherically projecting fiber tracts, in the peak area of parallel FA and Mode increase.