Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders

Abstract

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders.

Keywords: Alzheimer; antioxidant; brain; flavonoids; neurodegeneration; neurogenesis; neuroinflammation; neuropathology; neuroplasticity; zebrafish.

Figure 1

Basic skeleton structure of flavonoids and its subclasses. Adapted with permission from [38]. 2021, Giuseppe Montalbano.

Figure 2

The different biological processes involved in the development of neurodegenerative diseases.

Figure 3

Schematic drawing of (A) a sagittal section of rodent (left), zebrafish (middle), and human (right) brains with the main neurogenic niches indicated in red. The mammalian brain displays only two main neurogenic niches: the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. The black lines correspond to coronal sections. (B,C): Transversal sections through the brain, marking the major neurogenic niches of the respective species shown in A. In zebrafish, the red dots correspond to slow-cycling progenitors (mainly radial glial cells, type 2), and the green ones to fast-cycling progenitors (mainly neuroblasts, type 3). OB, olfactory bulbs; Ce, cerebellum; D, telencephalic dorsal area; Hyp, hypothalamus; RMS, rostral migratory stream; Dm, dorsomedial zone of the dorsal telencephalon; Dc, central zone of the dorsal telencephalon; Dl, lateral zone of the dorsal telencephalon; Dp, posterior zone of the dorsal telencephalon; Vd, dorsal nucleus of the ventral telencephalon; Vv, ventral nucleus of the ventral telencephalon. This figure is adapted from [296,297].