Galectin-3 Deletion Reduces LPS and Acute Colitis-Induced Pro-Inflammatory Microglial Activation in the Ventral Mesencephalon

Abstract

Parkinson’s disease is a highly prevalent neurological disorder for which there is currently no cure. Therefore, the knowledge of risk factors as well as the development of new putative molecular targets is mandatory. In this sense, peripheral inflammation, especially the originated in the colon, is emerging as a predisposing factor for suffering this disease. We have largely studied the pleiotropic roles of galectin-3 in driving microglia-associated immune responses. However, studies aimed at elucidating the role of galectin-3 in peripheral inflammation in terms of microglia polarization are lacking. To achieve this, we have evaluated the effect of galectin-3 deletion in two different models of acute peripheral inflammation: intraperitoneal injection of lipopolysaccharide or gut inflammation induced by oral administration of dextran sodium sulfate. We found that under peripheral inflammation the number of microglial cells and the expression levels of pro-inflammatory mediators take place specifically in the dopaminergic system, thus supporting causative links between Parkinson’s disease and peripheral inflammation. Absence of galectin-3 highly reduced neuroinflammation in both models, suggesting an important central regulatory role of galectin-3 in driving microglial activation provoked by the peripheral inflammation. Thus, modulation of galectin-3 function emerges as a promising strategy to minimize undesired microglia polarization states.

Novel Galectin-3 Roles in Neurogenesis, Inflammation and Neurological Diseases

“…We also found that many other chemokine and cytokine expression profiles were decreased in Gal-3 −/− mice after TMEV (Table S2) [50]. More recent work upholds the general principle that Gal-3 is pro-inflammatory in the CNS by showing that absence of Gal-3 reduces neuroinflammation in acute peripheral inflammation mouse models [157].…”

“…Gal-3 is upstream and required for several pro-inflammatory molecules in MS. Microglia are recruited to the pro-inflammatory milieu of EAE, which Jiang et al ( 2009) studied extensively. Gal-3 −/− lymph nodes produced less interleukin 17 (IL-17), interferon gamma (IFN-γ) and IL-6 in the presence of EAE-inducing myelin oligodendrocyte glycoprotein antigen [157]. In the CNS, Gal-3 −/− mice but not WT mice had detectable IL-17, IFN-γ, tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (NOS) transcripts.…”

Inflammatory Animal Models of Parkinson’s Disease

“…Melatonin, fermented rice brand, and DHA/EPA treatments also improve the symptoms associated to peripheral inflammation-related neuroinflammation [153][154][155]. In this regard, our group has recently published a study on the peripheral and central anti-inflammatory effects of galectin-3 inhibitors in DSS-induced gut inflammation [129].…”

“…In this sense, Boza-Serrano et al have shown that modulation of galectin-3, a microglia-related protein recently described as an immunomodulator, plays a significant role in microglia activation induced by α-syn [ 128 ]. Indeed, we have demonstrated that this ability of galectin-3 is extensive to emerge as a promising strategy to minimize undesired microglia activation states in PD [ 129 ]. The use of anti-inflammatory therapies in PD treatment has also been proposed, although clinical trials do not show significant results [ 130 ].…”

Association between sleep patterns and galectin-3 in a Chinese community population

“…Recent research studies have established a connection between galectin-3 and both peripheral information and neuroinflammation, with positive associations noted between galectin-3 and cardiovascular as well as neurodegenerative diseases [ 14 , 15 ]. Galectin-3 has been identified as a central upstream regulator of the immune response in Alzheimer’s disease [ 16 ]. It has also been observed that galectin-3 levels increase significantly in patients with Obstructive Sleep Apnea (OSA), and this increase further promotes neuroinflammation and oxidative stress via regulating NLRP3 [ 17 ].…”