The Evolution of Chimpanzee Sanctuaries in the United States

Chimpanzees are native only to the jungles of equatorial Africa, but for the last hundred years, they have also lived in captivity in the United States, most commonly in biomedical research laboratories, but also at Air Force bases for experiments for the space program, at accredited and unaccredited zoos, at circuses, as performers in Hollywood and even in private homes and backyards as pets. But that has been gradually evolving over the last few decades, as more and more chimpanzees move to newly-established chimpanzee sanctuaries. That transition was already underway even before the announcement by the National Institutes of Health (NIH) last year that it will retire all of its remaining chimpanzees from labs to sanctuaries. By thoroughly examining the evolution of these sanctuaries leading up to that seminal decision, along with the many challenges they face, including money, medical care, conflicting philosophies on the treatment of animals and the pitfalls that have led other sanctuaries to the brink of ruin, we can take away a better understanding of why chimpanzee sanctuaries are needed and why caretakers of other animal species are now looking to the chimpanzee sanctuary movement as a model to show how animals can be cared for in retirement.

Transient Receptor Potential Vanilloid 4 Ion Channel Functions as a Pruriceptor in Epidermal Keratinocytes to Evoke Histaminergic Itch.

TRPV4 ion channels function in epidermal keratinocytes and in innervating sensory neurons; however, the contribution of the channel in either cell to neurosensory function remains to be elucidated. We recently reported TRPV4 as a critical component of the keratinocyte machinery that responds to ultraviolet B (UVB) and functions critically to convert the keratinocyte into a pain-generator cell after excess UVB exposure. One key mechanism in keratinocytes was increased expression and secretion of endothelin-1, which is also a known pruritogen. Here we address the question of whether TRPV4 in skin keratinocytes functions in itch, as a particular form of "forefront" signaling in non-neural cells. Our results support this novel concept based on attenuated scratching behavior in response to histaminergic (histamine, compound 48/80, endothelin-1), not non-histaminergic (chloroquine) pruritogens in Trpv4 keratinocyte-specific and inducible knock-out mice. We demonstrate that keratinocytes rely on TRPV4 for calcium influx in response to histaminergic pruritogens. TRPV4 activation in keratinocytes evokes phosphorylation of mitogen-activated protein kinase, ERK, for histaminergic pruritogens. This finding is relevant because we observed robust anti-pruritic effects with topical applications of selective inhibitors for TRPV4 and also for MEK, the kinase upstream of ERK, suggesting that calcium influx via TRPV4 in keratinocytes leads to ERK-phosphorylation, which in turn rapidly converts the keratinocyte into an organismal itch-generator cell. In support of this concept we found that scratching behavior, evoked by direct intradermal activation of TRPV4, was critically dependent on TRPV4 expression in keratinocytes. Thus, TRPV4 functions as a pruriceptor-TRP in skin keratinocytes in histaminergic itch, a novel basic concept with translational-medical relevance.