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

Paolo De Girolamo,Livia D’Angelo,Chiara Attanasio,Carla Lucini,Adele Leggieri,Antonio Palladino

doi:10.3390/brainsci10060394

Paolo De Girolamo, Livia D’Angelo + Show 4 more

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https://doi.org/10.3390/brainsci10060394

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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.

Highlights

The brain of teleost fish has received much attention in the last decades, with regards to basic and applied neuroscientific research [1,2]
We investigated the neuroanatomical organization of the cholinergic system and we questioned whether cholinergic neurons were NTRK1/NTRKA and p75/NGFR expressing neurons in the brain of N. furzeri
According to the homologies with mammals, we defined three relevant groups of cholinergic neurons in N. furzeri. (a) Ch-1: choline acetyl-transferase (ChaT) immunoreactive cells in the ventral telencephalon, considered the fish subpallium, are likely homologous to cholinergic septal neuron populations in tetrapods and represent a well-conserved cell group found in fishes, amphibians, reptiles, birds and mammals [81]; (b) Ch-2: the cholinergic cells identified in the preoptic area, documented in other teleosts [47,48,50,53,81], correspond functionally to the mammalian basal forebrain cholinergic groups [59]; (c) Ch-3: the cholinergic cells observed in the rostral reticular nucleus, are equivalent to the pedunculopontine nucleus and dorsolateral tegmental group of mammals

Summary

Introduction

The brain of teleost fish has received much attention in the last decades, with regards to basic and applied neuroscientific research [1,2]. The most well studied model organism is. The process of brain aging in the teleost has received much less attention so far [4,5]. The African turquoise killifish, Nothobranchius furzeri, has emerged as a powerful model, due to its natural lifespan ranging between 4 and 9 months, related ageing hallmarks and the available approaches for experimentally modulating the lifespan [6,7]. In the course of aging, N. furzeri shows reduced learning performances, paralleled by gliosis and reduced adult neurogenesis [4]. Brain displays evolutionary conserved miRNA regulation [8,9]

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