Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair

Abstract

Adiponectin and its receptors (adipor) have been initially characterized for their role in lipid and glucose metabolism. More recently, adiponectin signaling was shown to display anti‐inflammatory effects and to participate in brain homeostasis and neuroprotection. In this study, we investigated adipor gene expression and its regulation under inflammatory conditions in two complementary models: mouse and zebrafish. We demonstrate that adipor1a, adipor1b, and adipor2 are widely distributed throughout the brain of adult fish, in neurons and also in radial glia, behaving as neural stem cells. We also show that telencephalic injury results in a decrease in adipor gene expression, inhibited by an anti‐inflammatory treatment (Dexamethasone). Interestingly, adiponectin injection after brain injury led to a consistent decrease (a) in the recruitment of microglial cells at the lesioned site and (b) in the proliferation of neural progenitors, arguing for a neuroprotective role of adiponectin. In a comparative approach, we investigate Adipor1 and Adipor2 gene distribution in the brain of mice and demonstrated their expression in regions shared with fish including neurogenic regions. We also document Adipor gene expression in mice after middle cerebral artery occlusion and lipopolysaccharide injection. In contrast to zebrafish, these inflammatory stimuli do no impact cerebral adiponectin receptor gene expression in mouse. This work provides new insights regarding adipor expression in the brain of fish, and demonstrates evolutionary conserved distribution of adipor with mouse. This is the first report of adipor expression in adult neural stem cells of fish, suggesting a potential role of adiponectin signaling during vertebrate neurogenesis. It also suggests a potential contribution of inflammation in the regulation of adipor in fish.

Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia

“…Notch signaling and associated molecular cascades are among the major determinants of neurogenesis by regulating the balance between quiescence and proliferation (Alunni et al, 2013; Berberoglu et al, 2014; Jiao et al, 2011; Kishimoto, Shimizu, & Sawamoto, 2012; T. Shimizu & Hibi, 2009; Than‐Trong et al, 2018) (Coolen et al, 2012; Coolen, Katz, & Bally‐Cuif, 2013; Katz et al, 2016). In addition to Notch, hyperglycemic conditions and hormonal signaling through estrogen were also shown to keep radial glial stem cell pool quiescent (Diotel et al, 2013, 2018; Dorsemans, Lefebvre et al, 2017; Dorsemans, Soule et al, 2017; Rastegar et al, 2019). Altogether, it appears that maintaining the quiescence in adult zebrafish brain is an important way for maintaining the life‐long proliferative ability of neural stem cells, as shown also for mouse brains (Costa, Gotz, & Berninger, 2010; Kalamakis et al, 2019; Llorens‐Bobadilla et al, 2015; Mizrak et al, 2019; Petrik et al, 2018; Robel, Berninger, & Gotz, 2011; Silva‐Vargas, Crouch, & Doetsch, 2013; Silva‐Vargas, Maldonado‐Soto, Mizrak, Codega, & Doetsch, 2016; Urban et al, 2016).…”

Conserved and Divergent Features of Adult Neurogenesis in Zebrafish

“…Several other hormones are known to regulate neurogenesis in rodents such as Ghrelin, Thyroid hormones, Adiponectin and Androgens, however, their action has not yet been investigated in zebrafish. Mapping the expression of their receptors in the brain could constitute a first step in determining whether these regulations are conserved across species (Rastegar et al, 2019).…”

Inhibition of miR-19a protects neurons against ischemic stroke through modulating glucose metabolism and neuronal apoptosis

“…One of the predicted targets, Adipor-2 (encoding for adiponectin receptor 2), was of particular interest for two reasons. First, adiponectin receptors have been shown to be expressed in specific neurogenic niches and associated with brain repair [23]. Secondly, Adipor-1 has been shown to mediate electroacupuncture mediated cerebral attenuation of cerebral I/R injury in diabetic mice [24].…”