Cholinergic System and NGF Receptors: Insights from the Brain of the Short-Lived Fish Nothobranchius furzeri

Abstract

Nerve growth factor (NGF) receptors are evolutionary conserved molecules, and in mammals are considered necessary for ensuring the survival of cholinergic neurons. The age-dependent regulation of NTRK1/NTRKA and p75/NGFR in mammalian brain results in a reduced response of the cholinergic neurons to neurotrophic factors and is thought to play a role in the pathogenesis of neurodegenerative diseases. Here, we study the age-dependent expression of NGF receptors (NTRK1/NTRKA and p75/NGFR) in the brain of the short-lived teleost fish Nothobranchius furzeri. We observed that NTRK1/NTRKA is more expressed than p75/NGFR in young and old animals, although both receptors do not show a significant age-dependent change. We then study the neuroanatomical organization of the cholinergic system, observing that cholinergic fibers project over the entire neuroaxis while cholinergic neurons appear restricted to few nuclei situated in the equivalent of mammalian subpallium, preoptic area and rostral reticular formation. Finally, our experiments do not confirm that NTRK1/NTRKA and p75/NGFR are expressed in cholinergic neuronal populations in the adult brain of N. furzeri. To our knowledge, this is the first study where NGF receptors have been analyzed in relation to the cholinergic system in a fish species along with their age-dependent modulation. We observed differences between mammals and fish, which make the African turquoise killifish an attractive model to further investigate the fish specific NGF receptors regulation.

Neurotrophins and Trk Neurotrophin Receptors in the Retina of Adult Killifish (Nothobranchius guentheri)

“…The data of the present investigation, together with the known evidence on N. furzeri [ 26 , 91 , 93 , 120 , 121 ] and other species [ 99 , 102 , 122 ] confirm the fundamental role of the neurotrophins/receptors system in the maintenance and modulation of excitatory input in retinal neurons. Consequently, it might also suggest a mode of autocrine action of the NT/Trks system in the retina of the adult N. guentheri .…”

“…However, evidence of NTs-Trks system expression in the retina of this experimental model is still scarce. According to the authors’ knowledge, only TrkB has been localized in the retina of one species of the Nothobranchius genus, N. furzeri [ 26 , 91 , 92 , 93 ].…”

“…in addition, BDNF was observed in the N. guentheri retina in the RPE, in the external and internal segment of photoreceptors layer, and in ACs in the INL. Localizing the BDNF is intriguing because it has been demonstrated that its decrease is associated with age-dependent macular degeneration and retinopathy [ 10 , 71 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 98 , 99 , 100 , 101 ].…”

Neuronal Phenotype of col4a1 and col25a1: An Intriguing Hypothesis in Vertebrates Brain Aging

“…The African turquoise killifish N. furzeri is the vertebrate with the shortest lifespan ever reported in captivity [21,22]. This unique feature is reflected in a very fast growth coupled with the relatively early expression of aging phenotypes at morphological, physiological [23,24], and behavioral levels [25]. Overall, N. furzeri shows typical teleost aging features enhanced by high incidence of age-dependent neoplasia, making this species a suitable model for studying the molecular mechanisms underlying the aging process [26].…”

Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models

“…It is in this context that we have focused our interest on exploring the age-related changes of NPY in the African turquoise killifish ( Nothobranchius furzeri ), an emerging but now also well-recognized, model organism for the study of aging processes. In this teleost fish, displaying the shortest lifespan ever reported in captivity [ 12 , 13 , 14 ], a rapid growth is associated with a relatively early expression of aging phenotypes at multiple levels (morphological, physiological, and behavioral) [ 15 , 16 , 17 ]. In this work we aim to analyze and compare the age-related central and peripheral regulation of NPY in the shortest- and longest-lived fish species, turquoise killifish and zebrafish ( Danio rerio ), respectively.…”