Functional Assays for Neurotoxicity Testing

Abstract

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral and physiological methods evaluate the functional consequences of disruption of neuronal communications. The underlying causes of certain behavioral alterations may be understood, but many do not have known direct associations with specific brain pathologies. In some cases, however, rapidly expanding mouse models (transgenic, knock-out) are providing considerable information on behavioral phenotypes of altered pathology. Behavior represents the integrated sum of activities mediated by the nervous system, and functional tests used for neurotoxicity testing tap different behavioral repertoires. These tests have an advantage over pathologic measures in that they permit repeated evaluation of a single animal over time to determine the onset, progression, duration, and reversibility of a neurotoxic injury. Functional assays range from a screening-level battery of tests to refined procedures to tap specific forms of learning and/or memory. This article reviews common procedures for behavioral toxicity testing and provides examples of chemical-specific neurobehavioral-pathological correlations in order to inform interpretation and integration of neuropathological and behavioral outcomes.

Phytochemical Analysis, Antioxidant, Antistress, and Nootropic Activities of Aqueous and Methanolic Seed Extracts of Ladies Finger (Abelmoschus esculentusL.) in Mice

“…Moreover, the spontaneous locomotor activity of the animals treated with extracts AE and ME (up to 2000 mg/kg) was not significantly altered. Spontaneous locomotor activity is an apical test of neuromotor function, representing the peak of neural integration, which has been used for decades to evaluate effects of chemical treatment [42]. In addition, normal body weight gains were observed in the extracts treated groups and there was no significant difference between relative organ weights, haematological parameters, and H&E histopathological staining among treatment groups (Tables 2 and 3; Figure 5).…”

Neurotoxicity may be an overlooked consequence of benzo[a]pyrene exposure that is relevant to human health risk assessment

“…For example, Morris water maze data have been used to derive the reference dose (RfD, estimated daily exposure to humans likely not leading to a deleterious effect during a lifetime [45]) for the neurobehavioral effects of 2,2 0 ,4,4 0 ,5,5 0 -hexabromodiphenyl ether [42]. In general the Morris water maze test is an established behavioural test to measure neurotoxicity [42] and is routinely used as the second tier of neurotoxicity evaluations [46].…”

CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology

“…The Irwin or modified Irwin tests (Irwin 1968) and the FOB (Moser 1991) remain the two most commonly used observational testing paradigms to assess drug-induced CNS adverse effects and are considered equivalent by ICH S7A guidelines. The Irwin and FOB tests can be conveniently applied to longitudinal study designs to assess dose range, duration, magnitude, and reversibility of behavior and physiological functions (Moser 1991(Moser , 2011. These behavioral tests are part of the safety pharmacology core battery studies performed in pharmaceutical industry to evaluate motor activity, behavioral changes, coordination, sensory/ motor reflex responses, and body temperature.…”