Page 446 - The Toxicology of Fishes

426 The Toxicology of Fishes

products are then transported throughout the cell to replenish cellular constituents. In addition, spent
cellular constituents are transported retrogradely from the processes to the cell body. The retrograde
transport also contains biochemical information related to the status of the environment in the distal
portion of the neuron. Spatial arrangement of the nervous system also requires maintenance of the
transmission of electrical pulses along the length of axons and across the synapses between neurons.
Maintenance of both intracellular and extracellular communication is, of course, essential to the proper
function of the nervous system.
In conclusion, the nervous system has a variety of unique structural characteristics that meet the
need for rapid cellular communication. These unique structural characteristics are primarily associated
with maintaining the integrity of the cell body and axon and the ability of the nerves to support
propagation of action potentials and synaptic transmission. Xenobiotics capable of disrupting ion
channels that are essential to maintaining and supporting proper ion balances or capable of disrupting
chemical transmission of potentials across synapses are capable of causing neurotoxic effects. As
discussed previously, the maintenance of aerobic respiration, high rates of protein and lipid synthesis,
and extensive transport of synthetic products from the cell body to the axon are critical for maintaining
structural and functional characteristics of the nervous system. Consequently, xenobiotics capable of
disrupting neuron-specific synthetic and metabolic pathways, modifying the products of these reactions,
or inhibiting or uncoupling aerobic metabolism can elicit adverse effects specific to the nervous system.
It is interesting to note that some fish species have evolved specific metabolic strategies for anoxic
conditions. Research suggests that anoxic-tolerant species may have decreased levels of excitatory
neurotransmitters and increased levels of inhibitory transmitters in the brain that enable metabolic
depression (Van Ginneken et al., 1996).

Manifestations of Neurotoxicity in Fish

Neurotoxic effects of chemicals are assessed by quantifying structural and functional responses at the
subcellular to organismal levels of biological organization. Functional observations at the organismal
and cellular levels can provide insights concerning potential sites and modes of action, while cellular
and biochemical responses can provide insights on molecular mechanisms of action. Cellular and
biochemical investigations can be used to identify neurotoxic potential, characterize the nature of
neurological effects, and determine the mechanisms by which chemicals produce neurotoxic effects
(Tilson, 1996). A significant challenge in developing investigative methods and associated bioassay
techniques lies in linking neuromorphological, neurochemical, and neurophysiological alterations with
functional (i.e., behavioral) observations (NRC, 1992). Many chemically induced biochemical, physio-
logical, or morphological perturbations have been reported in cellular and organismal systems, but
consequent behavioral effects on organism have not been established. Because behavioral responses are
an integration of biochemical, physiological, and morphological processes, linking behavioral observa-
tions to these types of observations can provide the needed bridge between subcellular and cellular
responses and ecological consequences (Little, 1990). Examples where chemically induced biochemical,
physiological, or morphological perturbations have been mechanistically linked to ecologically relevant
behavioral responses in fish are limited.

Structural Manifestations of Neurotoxicity in Fish
As discussed previously, dynamic interactions between the neuronal cell body and the axon are critical
to maintaining proper neuronal structure and function. Disruption of these interactions can result in a
variety of pathologies. Neuronopathies result from toxicants capable of causing injury to the cell body
followed by degeneration of the remaining cell processes. Neuronal loss is typically permanent and is
manifested by global symptoms or dysfunctions consistent with the specific nervous tissue target; for
example, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes neuronopathies in mammals
through its cytotoxic dihydropyridium ion metabolite. Similar observations have been reported in fish