Chemotherapy accelerates age-related development of tauopathy and results in loss of synaptic integrity and cognitive impairment
| Autor: | Angie C.A. Chiang, Annemieke Kavelaars, Cobi J. Heijnen, Xiao Jiao Huo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Aging Drug-Related Side Effects and Adverse Reactions Microtubule-associated protein Immunology Hippocampus tau Proteins Article White matter Mice 03 medical and health sciences Behavioral Neuroscience Cognition 0302 clinical medicine Drug Therapy Glial Fibrillary Acidic Protein Animals Medicine Cognitive Dysfunction Cognitive decline biology Endocrine and Autonomic Systems business.industry Age Factors Brain Cancer medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Tauopathies Synaptophysin biology.protein Tauopathy Cisplatin business Neuroscience 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Brain Behav Immun |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2019.04.005 |
| Popis: | Cancer and its treatment are associated with neurotoxic side effects, including cognitive dysfunction, altered functional connectivity in the brain and structural abnormalities in white matter. There is evidence that cancer and its treatment can accelerate aging. Tau is a microtubule associated protein that contributes to microtubule stability thereby playing a key role in neuronal function. Clustering of tau is commonly observed in the aged brain and is related to cognitive decline. We hypothesized that chemotherapy-induced cognitive impairment is associated with accelerated development of tau clustering in the brain as a sign of accelerated aging. We show for the first time that treatment of adult (7–8 month-old) male C57BL/6 mice with cisplatin results in reduced cognitive function and a marked increase in the number of large endogenous tau clusters in the hippocampus when assessed 4 months later. In contrast, we detected only few small tau clusters in the hippocampus of age-matched 11–12 month-old control mice. Astrocyte GFAP expression was increased in close vicinity to the tau clusters in cisplatin-treated mice. We did not detect changes in the microglial marker Iba-1 in the brain of mice treated with cisplatin. The accelerated formation of Tau-1 clusters in cisplatin-treated mice was associated with a decrease in the levels of the post-synaptic marker PSD95 and of the presynaptic marker synaptophysin in the hippocampus. We demonstrate here for the first time that chemotherapy markedly accelerates development of signs of tauopathy and loss of synaptic integrity in the hippocampus. These findings provide a mechanistic link between chemotherapy cognitive decline and accelerated aging in cancer survivors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect