Vijayakumar S, Masood A, Smith M, Clark JP, Nelson DE, Ding JM (2005) Immunolesion of p75 NGF receptor in the mouse SCN attenuated light-induced phase shift of the circadian wheel-running rhythm. Neuroscience 2005 Abstracts 766.18. Society for Neuroscience, Washington, DC.
Summary: Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus. Alhough the SCN can orchestrate these rhythms in the absence of external cues, it is entrained to environmental cycles through the retinohypothalamic tract. Light-induced phase shifts in circadian rhythm is a classic example of short-term environmental stimuli inducing lasting changes in intracellular signals and gene expression within the SCN cells that alter the phase of the SCN pacemaker and allow entraiment. Since neurotrophins are known to mediate neural plasticity, we investigated the role of brain-derived neurotrophic factor (BDNF) on resetting the phase of the SCN both in vitro and in vivo. We used the SCN brain slice model to study the direct effect of BDNF on the circadian rhythm. Briefly, coronal hypothalamic slices containing the SCN were prepared using 129B/6 mice. The circadian rhythm of the SCN neurons in the brain slice was monitored for 2-3 days by continuously sampling the spike frequencies with single-unit extracellular electrodes. Brief microdrop applications of BDNF (10 uM) induced robust phase delays at CT 16 and phase advances at CT 22. BDNF binds to neurotrophin receptors, including the low affinity p75NTR, which is localized in the SCN. When the toxin Saporin is conjugated to the antibody against p75NTR, it selectively destroys the cells expressing the p75NTR. Three weeks after the stereotaxic injection of the mu p75-Saporin (Advanced Targeting System) into the third ventricle (1 ul over 20 min), the p75NTR immunoreactivity in the mouse SCN is abolished. Immunolesion of the p75NTR in the SCN attenuated light-induced phase delays of the wheel running rhythm at CT16. Consistent with previous findings, our results support a role for BDNF and its receptor p75NTR, in resetting the circadian rhythm of the SCN in mice.
Related Products: mu p75-SAP (Cat. #IT-16)