Squid (Loligo pealei) Giant Fiber System: A Model for Studying Neurodegeneration and Dementia?

Abstract

Abstract. In many neurodegenerative disorders that lead to memory loss and dementia, the brain pathology responsible for neuronal loss is marked by accumulations of proteins in the form of extracellular plaques and intracellular filamentous tangles, containing hyperphosphorylated cytoskeletal proteins. These are assumed to arise as a consequence of deregulation of a normal pattern of topographic phosphorylation-that is, an abnormal shift of cytoskeletal protein phosphorylation from the normal axonal compartment to cell bodies. Although decades of studies have been directed to this problem, biochemical approaches in mammalian systems are limited: neurons are too small to permit separation of cell body and axon compartments. Since the pioneering studies of Hodgkin and Huxley on the giant fiber system of the squid, however, the stellate ganglion and its giant axons have been the focus of a large literature on the physiology and biochemistry of neuron function. This review concentrates on a host of studies in our laboratory and others on the factors regulating compartment-specific patterns of cytoskeletal protein phosphorylation (primarily neurofilaments) in an effort to establish a normal baseline of information for further studies on neurodegeneration. On the basis of these data, a model of topographic regulation is proposed that offers several possibilities for further studies on potential sites of deregulation that may lead to pathologies resembling those seen in mammalian and human brains showing neurodegeneration, dementia, and neuronal cell death.

ESTs library from embryonic stages reveals tubulin and reflectin diversity in Sepia officinalis (Mollusca — Cephalopoda)

“…This zoological group belongs to, but is very derived within Mollusca, with highly specialized structures (funnel and arms derived from the mollusks' foot, muscular mantle) and a large and sophisticated nervous system including a "brain" resulting from the fusion of the main nervous ganglia (Budelmann, 1995). This brain, as well as the giant axon system, has been extensively studied; these structures are always considered as useful models in neurophysiology (Grant et al, 2006;Hochner et al, 2006;Walters and Moroz, 2009;Williamson and Chrachri, 2004). In addition, cephalopods begin to be considered of special interest for developmental and evolutionary studies.…”

Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases

“…However, such strategies require knowledge of mechanisms underlying loss of connectivity in the context of each AOND (Conforti et al, 2007; Gerdts et al, 2016; Luo and O’Leary, 2005). Unfortunately, the study of mechanisms has been hampered in part due to the scarcity of experimental systems designed to study axon and synapse-specific molecular events in isolation (Grant et al, 2006; Leopold et al, 1994; Llinas et al, 1992). …”

“…Another set of neuronal proteins commonly exhibiting altered phosphorylation in AONDs are the abundant neurofilament subunits NFH and NFM (Grant and Pant, 2000; Grant et al, 2006; Julien and Mushynski, 1998). Accumulation of highly phosphorylated neurofilaments in the initial segment of motor neuron axons is a major hallmark of ALS (Ackerley et al, 2004; Xiao et al, 2006), and many other unrelated AONDs display changes in neurofilament phosphorylation (Holmgren et al, 2012).…”

Invertebrate Models for Biomedical Research, Testing, and Education

“…Because of their giant axons, fi bers, and synapses, octopi and squid are often used as research and teaching models for neurobiology (Grant et al 2006;Van Heukelem 1977). The Yucatan octopus (O. maya), which can easily be grown under laboratory conditions, is used as both a teaching and research model for comparative psychology and neurobiology (Van Heukelem 1977).…”