The suprachiasmatic nuclei (SCN), the location of the mammalian circadian clock, are one of the few adult brain regions that express the highly polysialylated form of neural cell adhesion molecule (PSA-NCAM). A role for the polysialic acid (PSA) component of PSA-NCAM, which is known to promote tissue plasticity, has been reported for photic entrainment of circadian rhythmicity in vivo. The in vivo results, however, do not discriminate between PSA acting upstream or downstream of the glutamatergic synapses that convey photic information to the SCN. To address this key issue, we exploited an in vitro rat brain slice preparation that retains robust circadian function. As in the intact SCN, PSA levels in the isolated SCN are rhythmic, with higher levels during the early subjective day and lower levels during subjective night. Importantly, bath application of glutamate to SCN slices rapidly and transiently increases PSA levels during both the subjective day and night. Pretreating the slices with endoneuraminidase, which selectively removes PSA from NCAM and thereby prevents this increase, abolishes glutamate- and optic chiasm stimulation-induced phase delays of the SCN circadian neuronal activity rhythm. These results support the hypothesis that PSA expression in the SCN is controlled by both the circadian clock and photic input to the clock and that expression of PSA in the SCN is critical for photic-like phase shifts of the clock. Together, these results establish that such actions of PSA are manifested downstream from presynaptic retinohypothalamic terminals and therefore are intrinsic to the SCN itself.

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Biotechnological innovation is gaining increased recognition as an important tool for improving global health. The challenge, however, lies in defining the role of technology transfer to develop therapies for diseases prevalent in developing countries. During the past decade, a large disparity emerged between the developed and developing world in accessing affordable medicines because of the pharmaceutical industry's focus on health areas bearing greatest profits. Discussed herein are several mechanisms that provide partial solutions to this challenge. The Office of Technology Transfer of the US National Institutes of Health has increased its technology licensing pertaining to neglected diseases to partners in developing regions. Establishing partnerships through the transfer of technologies and assisting indigenous institutions build R and D capacity may positively impact policies on protection of intellectual property rights and increase multinational company investments in lesser-developed countries. This will most probably result in the development of more accessible therapies for those in need.

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