Antagonism of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus disrupts the rhythm of FRAs expression in neuroendocrine dopaminergic neurons

Jul 19, 2002The Journal of comparative neurology

Blocking a key brain signal in the body’s internal clock disrupts daily activity patterns in dopamine-producing nerve cells that control hormones

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Abstract

The proportion of neuroendocrine dopaminergic neurons expressing Fos-related antigens (FRAs) was significantly lower at 7:00 PM compared to other time points.

Fos-related antigens expression in neuroendocrine dopaminergic neurons peaked at 7:00 AM, 9:00 AM, 12:00 PM, and 12:00 AM, showing a clear daily rhythm.
A subpopulation of vasoactive intestinal peptide (VIP) neurons in the suprachiasmatic nucleus expressed cFos maximally at 7:00 AM, with no expression at 7:00 PM and 12:00 AM.
Injection of antisense VIP oligonucleotides into the SCN reduced VIP protein levels and maintained higher FRAs expression in neuroendocrine dopaminergic neurons at 7:00 PM.
The observed patterns suggest a possible mechanism where SCN VIP fibers may convey time-of-day signals to control neuroendocrine dopaminergic neuron activity.

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This study was designed to determine whether there is a functional relationship between cfos expression in vasoactive intestinal peptide (VIP) -containing neurons of the suprachiasmatic nucleus (SCN) and Fos-related antigens (FRAs) expression in neuroendocrine dopaminergic neurons of the arcuate (ARN) and periventricular (PeVN) nuclei of the hypothalamus. Brains were obtained from ovariectomized (OVX) female rats killed at 12:00 AM, 7:00 AM, 9:00 AM, 12:00 PM, and 7:00 PM (12 hours illumination beginning 6:00 AM). Antibodies against FRAs and tyrosine hydroxylase (TH) identified activated neuroendocrine dopaminergic neurons. Antibodies against cfos and VIP identified activated VIP-immunoreactive (IR) neurons in the SCN. The proportion of neuroendocrine dopaminergic neurons in the ARN and PeVN expressing FRAs was greatest and equivalent at 7:00 AM, 9:00 AM, 12:00 PM, and 12:00 AM. At 7:00 PM, the proportion of neuroendocrine dopaminergic neurons expressing FRAs was significantly lower than all other time points. In the SCN, a subpopulation of VIP-IR neurons maximally expressed cfos at 7:00 AM, which decreased through 9:00 AM. cFos was not expressed at 7:00 PM and 12:00 AM in VIP-IR neurons. Antisense VIP oligonucleotides were injected into the SCN to determine whether attenuation of VIP expression disturbs rhythms in neuroendocrine dopaminergic neuronal activity. OVX rats were infused with either antisense VIP oligonucleotides or scrambled sequence oligonucleotides bilaterally (0.5 microg in 0.5 microl of saline per side) in the SCN. Animals were killed 34 hours (7:00 PM) and 46 hours (7:00 AM) after receiving infusions, and brains were recovered. Administration of antisense VIP oligonucleotides decreased VIP protein expression in the SCN and prevented the decrease in the percentage of neuroendocrine dopaminergic neurons expressing FRAs at 7:00 PM but did not affect FRAs expression at 7:00 AM when compared with animals receiving scrambled oligonucleotides. These data suggest that VIP fibers from the SCN may relay time-of-day information to neuroendocrine dopaminergic neurons to inhibit their activity and, thus, initiate prolactin release in the evening.

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Antagonism of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus disrupts the rhythm of FRAs expression in neuroendocrine dopaminergic neurons

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