Neuronal degeneration and regeneration induced by axotomy in the olfactory epithelium of Xenopus laevis

Abstract

The olfactory epithelium (OE) has the remarkable capability to constantly replace olfactory receptor neurons (ORNs) due to the presence of neural stem cells (NSCs). For this reason, the OE provides an excellent model to study neurogenesis and neuronal differentiation. In the present work, we induced neuronal degeneration in the OE of Xenopus laevis larvae by bilateral axotomy of the olfactory nerves. We found that axotomy induces specific- neuronal death through apoptosis between 24 and 48h post-injury. In concordance, there was a progressive decrease of the mature-ORN marker OMP until it was completely absent 72h post-injury. On the other hand, neurogenesis was evident 48h post-injury by an increase in the number of proliferating basal cells as well as NCAM-180- GAP-43+ immature neurons. Mature ORNs were replenished 21 days post-injury and the olfactory function was partially recovered, indicating that new ORNs were integrated into the olfactory bulb glomeruli. Throughout the regenerative process no changes in the expression pattern of the neurotrophin Brain Derivate Neurotrophic Factor were observed. Taken together, this work provides a sequential analysis of the neurodegenerative and subsequent regenerative processes that take place in the OE following axotomy. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1308-1320, 2017.

Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

“…During the process of regeneration stem cell proliferation in the MOE initiates a compensatory increase in immature neurons expressing NCAM-180 (Cervino et al, 2017 ). Eventually, this leads to an elevation of functional ORNs over the course of 1 week after ON transection (this study).…”

“…This is similar to newborn ORNs in the rodent MOE that are mature after 7–8 days expressing olfactory marker protein (Miragall and Graziadei, 1982 ). In Xenopus , recovery of OMP-expression in newly generated ORNs takes longer than 7 days and remains reduced even 4 weeks post-transection (Cervino et al, 2017 ). Already after 1 week, other surveyed parameters in the Xenopus MOE, e.g., functional odorant responses, return to control levels.…”

“…In our study, the structural and functional recovery of the olfactory system of Xenopus laevis larvae after ON transection took 7 weeks. A recovery of specific foraging behavior in response to food-odor occurs 3 weeks after ON transection (Cervino et al, 2017 ). Notably, newly formed ORN synapses in larval Xenopus show a high vesicle density in their active zones and can be active before the glomerular units of the OB are fully restored (Terni et al, 2017 ).…”

Three‐dimensional reconstruction of the cranial and anterior spinal nerves in early tadpoles of Xenopus laevis (Pipidae, Anura)

“…Since the mid‐20th century, the African clawed frog, Xenopus laevis , has become one of the most widely used model organisms in biology (Harland & Grainger, ; Porro & Richards, ). Especially in neurobiology, Xenopus embryos, tadpoles, and adults are used as models in pathological, developmental, physiological, and behavioral studies (Cannatella & De Sa, ; Cervino, Paz, & Frontera, ; Cline & Kelly, ; Dong et al, ; Edwards‐Faret et al, ; Frankenhaeuser & Huxley, ; Gouchie, Roberts, & Wassersug, ; Katz, Potel, & Wassersug, ; Lee‐Liu, Méndez‐Olivos, Muñoz, & Larraín, ; McKeown, Sharma, Sharipov, Shen, & Cline, ; Moreno, Tapia, & Larrain, ; Pieper, Eagleson, Wosniok, & Schlosser, ; Pratt & Khakhalin, ; Roberts, Walford, Soffe, & Yoshida, ; Schlosser & Northcutt, ; Simmons, Costa, & Gerstein, ; Wassersug & Hessler, ; Young & Poo, ). It is therefore surprising, that only one study (Paterson, ) on the anatomy of the cranial nerves of X. laevis tadpoles exists.…”

Olfactory neuron turnover in adultDrosophila

“…Our results showing apoptosis and generation of OSN over time support an ongoing turnover in the olfactory system of adult flies. Whether OSN regenerate following injury, as it occurs in vertebrates (Graziadei et al, 1978;McM Carr and Farbman, 1992;Schwob et al, 1995;Frontera et al, 2016;Cervino et al, 2017), and how ageing affects this capacity, are questions that can be addressed in future experiments using the platform presented here. Furthermore, this platform will facilitate and expedite the screening of molecules promoting proliferation and integration of neurons in an entire adult circuit (Fernández-Hernández et al, 2016).…”