Impaired constitutive and regenerative neurogenesis in adult hyperglycemic zebrafish

Abstract

A growing body of evidence supports hyperglycemia as a putative contributor to several brain dysfunctions observed in diabetes patients, such as impaired memory capacity, neural plasticity, and neurogenic processes. Thanks to the persistence of radial glial cells acting as neural stem cells, the brain of the adult zebrafish constitutes a relevant model to investigate constitutive and injury-induced neurogenesis in adult vertebrates. However, there is limited understanding of the impact of hyperglycemia on brain dysfunction in the zebrafish model. This work aimed at exploring the impact of acute and chronic hyperglycemia on brain homeostasis and neurogenesis. Acute hyperglycemia was shown to promote gene expression of proinflammatory cytokines (il1β, il6, il8, and tnfα) in the brain and chronic hyperglycemia to impair expression of genes involved in the establishment of the blood-brain barrier (claudin 5a, zona occludens 1a and b). Chronic hyperglycemia also decreased brain cell proliferation in most neurogenic niches throughout the forebrain and the midbrain. By using a stab wound telencephalic injury model, the impact of hyperglycemia on brain repair mechanisms was investigated. Whereas the initial step of parenchymal cell proliferation was not affected by acute hyperglycemia, later proliferation of neural progenitors was significantly decreased by chronic hyperglycemia in the injured brain of fish. Taken together, these data offer new evidence highlighting the evolutionary conserved adverse effects of hyperglycemia on neurogenesis and brain healing in zebrafish. In addition, our study reinforces the utility of zebrafish as a robust model for studying the effects of metabolic disorders on the central nervous system. J. Comp. Neurol. 525:442-458, 2017. © 2016 Wiley Periodicals, Inc.

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

“…PCNA, S100β, and GFAP antibodies have been previously documented for their use and their specificity in mouse and in zebrafish according to manufacturer's instruction and/or literature (Diotel et al, ; Diotel, Beil, et al, ; Dorsemans, Soule, et al, ; Marz et al, ). Consistent with these previous studies, PCNA‐labeling was observed in cell nuclei across the neurogenic niches lining the ventricles.…”

“…For mouse, immunohistochemistry was performed on 12 μm thickness transverse cryostat sections. Briefly, the brain sections were blocked with blocking buffer (BB; PBS containing 0.1% Tween-10, 0.2% bovine serum albumin, 1% dimethyl sulfoxide) and 2.9 | Antibodies specificity PCNA, S100β, and GFAP antibodies have been previously documented for their use and their specificity in mouse and in zebrafish according to manufacturer's instruction and/or literature Diotel, Beil, et al, 2015;Dorsemans, Soule, et al, 2017;Marz et al, 2010). Consistent with these previous studies, PCNA-labeling was observed in cell nuclei across the neurogenic niches lining the ventricles.…”

“…Zebrafish has become a well‐recognized model for studying metabolic disorders, (Krishnan & Rohner, ; Zang, Maddison, & Chen, ) as well as brain physiology and brain repair mechanisms (Baumgart, Barbosa, Bally‐Cuif, Gotz, & Ninkovic, ; Diotel et al, , ; Diotel, Beil, Strahle, & Rastegar, ; Dorsemans et al, ; Kishimoto, Shimizu, & Sawamoto, ; Kizil, Kaslin, Kroehne, & Brand, ; Rodriguez Viales et al, ; Schmidt, Beil, Strähle, & Rastegar, ; Zupanc, ). In contrast to mammals, zebrafish display a widespread neurogenic activity through the whole encephalon (Lindsey & Tropepe, ).…”

Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and zebrafish models

“…19,107,108 Zebrafish is also a common model for investigating a wide variety of physiologic and physiopathological processes including metabolic syndrome and diabetes. [109][110][111][112][113] T2D has been developed by immersing fish in water supplemented with D-glucose, 109,111,114 and T1D has been set up by STZ intraperitoneal (ip) injection. 109 Acute hyperglycemia can be also mimicked by intraperitoneal injection of D-glucose.…”

“…109 Acute hyperglycemia can be also mimicked by intraperitoneal injection of D-glucose. 112 Consequently, zebrafish appear as interesting models for investigating the role of metabolic disorders such as diabetes on the CNS.…”