Changes in NGF Receptor-Like Immunoreactive Substance in the Suprachiasmatic Nucleus of the Hypothalamus in Blind Rats.

Abstract

Summaryin mammals, the hypothalamic suprachiasmatic nucleus (SCN ), a circadian oscillator, receives the retinohypothalamic tract (RHT), which is essential for the synchronization of circadian rhythms by light-dark cycle; and nerve growth factor (NGF) receptors with low affinity have been detected in the SCN. Thus, we examined whether low-affinity NGF receptors (LNGFR) are present in the terminals of the RHT by studies on the LNGFR-like immunoreactive substance (LNGFRLIS) in the SCN of blind rats. LNGFRLIS in the SCN gradually decreased with age in control rats, though it could be observed until 16-20 weeks of age. After bilateral orbital enucleation of 4-week-old rats, the density of the LNGFRLIS gradually decreased on both sides of the SCN from week 4 after the operation, disappearing 7 weeks after the operation. In congenitally blind, hereditary microphthalmic rats, LNGFRLIS was not detectable in the SCN, but in half-blind hereditary microphthalmic rats LNGFRLIS was detectable on both sides of the SCN. 125I-NGF injected into the SCN was found in the optic nerve and the retina. Since NGF is suggested to be retrogradely transported and to support survival of neurons, these findings suggest that LNGFR is present at the terminal of the RHT, and raise the possibility that NGF or other growth factors such as brain-derived neurotrophic factor in or around the SCN plays a role in maintaining the retinal ganglion cells through LNGFR.

Mice Lacking the p75NGFR Receptor Exhibit Abnormal Responses to Light

“…A role for NGF in either the generation or regulation of circadian rhythms in rodents is suggested from anatomical studies that demonstrate a dense expression of the low affinity receptor, p75 NGFR , in the SCN (Sofroniew et al 1989;Asada et al 1992;Bina et al, 1992). In hamsters, administration of NGF directly to the SCN produced phase shifts of freerunning rhythms that were similar to photic responses in both direction and circadian phase dependence (Bina and Rusak, 1991;Golombek et al, 1995).…”

“…In the rat SCN, this receptor has been shown to be co-localized with neurons that express vasoactive intestinal polypeptide (VIP) (Kiss et al, 1993) and which receive retinal input via the RHT (Okamura et al, 1987). Decreases in p75 NGFR immunoreactivity in this nucleus are found in blind (Asada et al 1992) and aged rats (Larkfors et al, 1987) where photic responses also may be reduced. This data suggests that NGF may be involved in the maintenance of RHT connections with SCN cells.…”

“…Recently the presence of the low affinity NGF receptor, p75 NGFR , has been demonstrated in the SCN with a distribution that corresponds to the RHT terminal field (Sofroniew et al 1989;Asada et al 1992;Bina et al, 1992). In the rat SCN, this receptor has been shown to be co-localized with neurons that express vasoactive intestinal polypeptide (VIP) (Kiss et al, 1993) and which receive retinal input via the RHT (Okamura et al, 1987).…”

Nerve growth factor‐induced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nuclei

“…The low‐affinity NGF receptor p75 NGFR is expressed in the nuclei with a distribution that corresponds to the RHT terminal field and has been shown to be co‐localized with vasoactive intestinal peptide (VIP)‐expressing SCN neurons (Kiss et al ., 1993), which receive retinal input via the RHT (Okamura et al ., 1995). Decreases in p75 NGFR immunoreactivity in these nuclei are found in blind (Asada et al ., 1992) and aged rats (Lärkfors et al ., 1987) where photic responses may also be reduced. Moreover, p75 NGFR ‐deficient mice exhibit abnormal responses to light (both under light–dark conditions and in response to entraining light pulses; Golombek & Ralph, 1996).…”