Anthocyanins control neuroinflammation and consequent memory dysfunction in mice exposed to lipopolysaccharide

Abstract

Peripheral inflammatory stimuli may activate a brain neuroinflammatory processes with consequences in brain function. The present study investigated if anthocyanins (ANT) consumption was able to prevent the memory loss, the neuronal damage, and the neuroinflammatory processes triggered by the intraperitoneal lipopolysaccharide (LPS) administration. C57BL6 male mice were treated with ANT (30-100 mg/kg by gavage). With a single dose or during 10 days, before be challenged with LPS (250 μg/kg intraperitoneally single administration), a classical inductor of inflammation. The data obtained showed that ANT was able to confer protection against the memory impairment after 10 days of ANT treatment (100 mg/kg). This phytonutrient also prevented the hypothermia episode induced by LPS. Moreover, ANT prevented the increase in protein carbonyl, NOx, and MDA levels in the hippocampus and cerebral cortex (4 and 24 h) in animal challenged with LPS. ANT showed a protective effect on the increase in the pro-inflammatory cytokines content, especially Interleukin (IL)-1β, tumoral necrosis factor-α and on the reduction of IL-10 induced by LPS. ANT 100 mg/kg prevented the infiltration of peripheral immune cells in the hippocampus at 24 h post-LPS administration. In parallel, LPS increased the activity of myeloperoxidase in cortex and hippocampus, and ANT prevented this effect, also reducing microglia (Iba-1) and astrocyte (GFAP) immunoreactivity. Thus, our data support that ANT are a promising therapeutic component against brain disorders associated with process of neuroinflammation. Graphical Abstract ᅟ.

Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases

“…IFNγ can also be released directly into the brain by PMBCs that have infiltrated the brain. Neutrophils and macrophages are capable of producing IFNγ and both infiltrate the brain following peripheral LPS injection (Carvalho et al, 2016; Jeong et al, 2010). By diminishing IFNγ expression by PBMCs, Desip can diminish IFNγ-production by PBMCs within the brain and thus reduce Ido induction.…”

Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases

“…This enhancement is confirmed by Western blot analysis of the memory-associated presynaptic and postsynaptic protein markers [ 239 , 240 ] and by behavioral tests. Anthocyanins improve learning and memory, which has been confirmed by the Morris water maze [ 240 , 243 , 244 , 245 , 252 , 253 , 254 , 260 , 264 , 265 , 266 ], Y-maze [ 240 , 255 ], novel object recognition [ 241 , 248 , 260 , 265 ] and passive avoidance [ 245 , 254 , 263 ] tests. Motor coordination is also improved by anthocyanins as confirmed by rotating rod test [ 244 ] and open-field [ 248 , 263 ] tests.…”

“…The antioxidant effect of anthocyanins in the brain is also confirmed in animal studies through oxidative biomarkers levels. Malondialdehyde (MDA) content decreases with anthocyanin treatment, as with black chokeberry extract in the d -galactose mouse model [ 244 ], with cyanidin-3- O -galactoside or blueberry extracts in senescence-accelerated mice prone 8 (SAMP8) mice [ 245 ], with pelargonidin in the amyloid β 25–35 (Aβ) rat model of AD [ 246 ] and with anthocyanins extracted from Korean black soybeans [ 247 ] and from bilberry [ 248 ] in LPS-injected mice. In the latter animal model, restoration of the levels of heat shock protein 70 after blueberry supplementation was also observed [ 249 ].…”

“…Activation of c-Jun-N-terminal kinase (JNK) in the brain is involved in microglia activation and induction of proinflammatory cytokine genes coding for TNF-α, IL-6, or MCP-1 in addition to cyclooxygenase-2 [ 253 ]. Anthocyanin administration to LPS-treated mice reverses JNK activation and decreases the levels of the following inflammatory markers: nuclear factor kappa B, TNF-α and IL-1β [ 242 , 247 , 248 ]. Moreover, anthocyanins reduced the overexpression of these inflammatory markers and lowered JNK levels in d -galactose ( d -gal)-treated rats [ 244 , 254 , 255 ].…”

Caffeine prevents high-intensity exercise-induced increase in enzymatic antioxidant and Na+-K+-ATPase activities and reduction of anxiolytic like-behaviour in rats

“…Reduction of Na + -K + -ATPase levels and activity directly impairs neurotransmitter signalling with deleterious consequences on learning and memory and increases locomotor activity and anxiety [12,13]. Impairment of Na + -K + -ATPase activity and/or mutations in its alpha subunits lead to neuronal dysfunction and may trigger depression, anxiety and bipolar disease [14,15,16].…”