Acute neuroinflammation provokes intracellular acidification in mouse hippocampus
Autor: | Larisa V. Lysenko, Anna Tyrtyshnaia, Igor Manzhulo, Maxim Khotimchenko, Alexander M. Kleschevnikov, Francisco Madamba |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Intracellular Fluid Lipopolysaccharides Male LPS Time Factors Intracellular pH Immunology Iba1 Interleukin-1beta Enzyme-Linked Immunosorbent Assay Biology In Vitro Techniques Hippocampus Acidification 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neuroinflammation Extracellular Animals Mouse Hippocampus General Neuroscience Research Extracellular pH Age Factors Extracellular Fluid Intracellular acidification Hydrogen-Ion Concentration Cell biology Mice Inbred C57BL BCECF Disease Models Animal 030104 developmental biology Neurology IL-1β Encephalitis Neuroscience 030217 neurology & neurosurgery Homeostasis |
Zdroj: | Journal of Neuroinflammation |
ISSN: | 1742-2094 |
Popis: | Background Maintaining pH levels within the physiological norm is an important component of brain homeostasis. However, in some pathological or physiological conditions, the capacity of the pH regulatory system could be overpowered by various factors resulting in a transient or permanent alteration in pH levels. Such changes are often observed in pathological conditions associated with neuroinflammation. We hypothesized that neuroinflammation itself is a factor affecting pH levels in neural tissue. To assess this hypothesis, we examined the effects of acute LPS-induced neuroinflammation on intra- and extracellular pH (pHi and pHo) levels in the CA1 region of mouse hippocampus. Methods Acute neuroinflammation was induced using two approaches: (1) in vivo by i.p. injections of LPS (5 mg/kg) and (2) in vitro by incubating hippocampal slices of naïve animals in the LPS-containing media (1 μg/mL, 1 h at 35 °C). Standard techniques were used to prepare hippocampal slices. pHi was measured using ratiometric pH-sensitive fluorescent dye BCECF-AM. pHo was assessed using calibrated pH-sensitive micropipettes. The presence of neuroinflammation was verified with immunohistochemistry (IL-1β and Iba1) and ELISA (IL-1β and TNF-α). Results A significant reduction of pHi was observed in the slices of the LPS-injected 3-month-old (LPS 7.13 ± 0.03; Sal 7.22 ± 0.03; p = 0.043, r = 0.43) and 19-month-old (LPS 6.78 ± 0.08; Sal 7.13 ± 0.03; p = 0.0001, r = 0.32) mice. In contrast, the levels of pHo within the slice, measured in 19-month-old animals, were not affected (LPS 7.27 ± 0.02; Sal 7.26 ± 0.02; p = 0.6, r = 0.13). A reduction of pHi was also observed in the LPS-treated slices during the interval 3.5–7 h after the LPS exposure (LPS 6.92 ± 0.07; Veh 7.28 ± 0.05; p = 0.0001, r = 0.46). Conclusions Acute LPS-induced neuroinflammation results in a significant intracellular acidification of the CA1 neurons in mouse hippocampus, while the pHo remains largely unchanged. Such changes may represent a specific protective reaction of neural tissue in unfavorable external conditions or be a part of the pathological process. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0747-8) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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