Non-human Primates in Neuroscience Research: The Case Against its Scientific Necessity

Jarrod Bailey and Katy Taylor

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP research generally, but here we specifically focus on the development and interpretation of functional magnetic resonance imaging (fMRI), deep brain stimulation (DBS), the understanding of neural oscillations and memory, and investigation of the neural control of movement and of vision/binocular rivalry. The increasing power of human-specific methods, including advances in fMRI and invasive techniques such as electrocorticography and single-unit recordings, is discussed. These methods serve to render NHP approaches redundant. We conclude that the defence of NHP use is groundless, and that neuroscience would be more relevant and successful for humans, if it were conducted with a direct human focus. We have confidence in opposing NHP neuroscience, both on scientific as well as on ethical grounds.

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Changes in Extracellular Action Potential Detect Kainic Acid and Trimethyltin Toxicity in Hippocampal Slice Preparations Earlier than do MAP2 Density Measurements

Raffaella Melani, Renata Rebaudo, Jens Noraberg, Jens Zimmer and Maurizio Balestrino

In vitro electrophysiological techniques for the assessment of neurotoxicity could have several advantages over other methods in current use, including the ability to detect damage at a very early stage, and could further assist in replacing animal experimentation in vivo. We investigated how an electrophysiological parameter, the extracellularly-recorded compound action potential (“population spike”, PS) could be used as a marker of in vitro neurotoxicity in the case of two well-known toxic compounds, kainic acid (KA) and trimethyltin (TMT). We compared the use of this electrophysiological endpoint with changes in immunoreactivity for microtubule-associated protein 2 (MAP2), a standard histological test for neurotoxicity. We found that both toxic compounds reliably caused disappearance of the PS, and that such disappearance occurred after only 1 hour of exposure to the drug. By contrast, densitometric measurements of MAP2 immunoreactivity were unaffected by both KA and TMT after such a short exposure time. We conclude that, in the case of KA and TMT, the extracellular PS was abolished at a very early time-point, when MAP2 immunoreactivity levels were still comparable to those of the untreated controls. Electrophysiology could be a reliable and early indicator of neurotoxicity, which could improve our ability to test for neurotoxicity in vitro, thus further replacing the need for in vivo experimentation.
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Detection of Electrophysiological Indicators of Neurotoxicity in Human and Rat Brain Slices by a Three-Dimensional Microelectrode Array

Rüdiger Köhling, Raffaella Melani, Uwe Koch, Erwin-Josef Speckmann, Milena Koudelka-Hep, Pierre Thiébaud and Maurizio Balestrino

Electrophysiological techniques for the assessment of in vitro neurotoxicology have several advantages over other currently-used methods (for example, morphological techniques), including the ability to detect damage at a very early stage. Novel recording techniques based on microelectrode arrays are available, and could improve recording power. In this study, we investigated how a three-dimensional microelectrode array detects the electrophysiological endpoints of neurotoxicity. We conclude that electrophysiology sensitively reveals neurotoxic actions, and that three-dimensional microelectrode arrays could be proposed for use in neurotoxicology as recording tools that allow easy and sensitive multisite recording, from both rodent and human brain tissue.
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Testing the Biocompatibility of a Glutathione-containing Intra-ocular Irrigation Solution by Using an Isolated Perfused Bovine Retina Organ Culture Model — an Alternative to Animal Testing

Kai Januschowski, Ahmad Zhour, Albert Lee, Ramin Maddani, Sebastian Mueller, Martin S. Spitzer, Sven Schnichels, Maximilian Schultheiss, Deshka Doycheva, Karl-Ulrich Bartz-Schmidt and Peter Szurman

The effects of a glutathione-containing intra-ocular irrigation solution, BSS Plus®, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD] = 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity.
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