Abstract: One of the changes found in the brain in Alzheimer’s disease (AD) is increased calpain, derived from calcium dysregulation, oxidative stress, and/or neuroinflammation, which are all assumed to be basic pillars in neurodegenerative diseases. The role of calpain in synaptic plasticity, neuronal death, and AD has been discussed in some reviews. However, astrocytic calpain changes sometimes appear to be secondary and consequent to neuronal damage in AD. Herein, we explore the possibility of calpain-mediated astroglial reactivity in AD, both preceding and during the amyloid phase. We discuss the types of brain calpains but focus the review on calpains 1 and…2 and some important targets in astrocytes. We address the signaling involved in controlling calpain expression, mainly involving p38/mitogen-activated protein kinase and calcineurin, as well as how calpain regulates the expression of proteins involved in astroglial reactivity through calcineurin and cyclin-dependent kinase 5. Throughout the text, we have tried to provide evidence of the connection between the alterations caused by calpain and the metabolic changes associated with AD. In addition, we discuss the possibility that calpain mediates amyloid-β clearance in astrocytes, as opposed to amyloid-β accumulation in neurons.
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Abstract: Although the exact cause of Alzheimer's disease remains elusive, many possible risk factors and pathological alterations have been used in the elaboration of in vitro and in vivo models of this disease in rodents, including intracerebral infusion of streptozotocin (STZ). Using this model, we evaluated spatial cognitive deficit and neurochemical hippocampal alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, glutathione content, nitric oxide production, and cerebrospinal fluid (CSF) S100B. In addition, prevention of these alterations by aminoguanidine administration was evaluated. Results confirm a spatial cognitive deficit and nitrative stress in this dementia model as…well as specific astroglial alterations, particularly S100B accumulation in the hippocampus and decreased CSF S100B. The hippocampal astroglial activation occurred independently of the significant alteration in GFAP content. Moreover, all these alterations were completely prevented by aminoguanidine administration, confirming the neuroprotective potential of this compound, but suggesting that nitrative stress and/or glycation may be underlying these alterations. These findings contribute to the understanding of diseases accompanied by cognitive deficits and the STZ-model of dementia.
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