Get access

Chromogranin mRNA Levels in the Brain as a Marker for Acute and Chronic Changes in Neuronal Activity: Effect of Treatments Including Seizures, Osmotic Stimulation and Axotomy in the Rat

Authors

  • P.-J. Shen,

    1. University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
    Search for more papers by this author
  • A. L. Gundlach

    Corresponding author
    1. University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
    Search for more papers by this author

Dr A. L. Gundlach, Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia

Abstract

Chromogranin/secretogranins are a family of acidic, soluble proteins with a widespread distribution in secretory vesicles of endocrine and nervous tissues. The effects of experimental stimuli of differing duration and intensity on chromogranin B and secretogranin II mRNA levels in relevant areas of the rat brain were examined by in situ hybridization histochemistry using 35S-labelled oligonucleotides. Effects of two ‘chronic stimulation’ paradigms were studied—the effect of 4 days of water or food deprivation on mRNA levels in the hypothalamus and the effect of unilateral cervical vagotomy on transcript levels in the dorsal vagal complex 1, 2 and 7 days after surgery. After 4 days of water deprivation secretogranin II mRNA was significantly increased in the supraoptic nucleus (366 ± 21% of control, P < 0.01), the magnocellular paraventricular nucleus (209 ± 20% of control, P < 0.01) and the parvocellular paraventricular nucleus (147 ± 6% of control, P < 0.01). Conversely, the level of secretogranin II mRNA in the supraoptic nucleus was decreased (61 ± 13% of control, P < 0.05) after 4 days of food deprivation. Seven days after unilateral cervical vagotomy, secretogranin II and chromogranin B mRNA levels were markedly decreased in the ipsilateral dorsal motor nucleus of the vagus (25 ± 4 and 47 ± 8% of contralateral values respectively, P < 0.01). Rapid changes in chromogranin mRNA were also detected following shorter duration ‘acute stimulation’—in the hypothalamus after hypertonic saline injection, in the hippocampus after electrical stimulation-induced kindled seizures, and in the cerebral cortex after unilateral craniotomy. A large increase in secretogranin II mRNA was detected in the supraoptic nucleus (202 ± 25% of control, P < 0.01) and the magnocellular paraventricular nucleus (168 ± 29% of control, P < 0.05) 3 h after a single intraperitoneal injection of hypertonic (1.8 M) saline. Markedly increased levels of secretogranin II (125–160% of control) and chromogranin B (140–230% of control) mRNA were observed in granule cells of the dentate gyrus 0.5–2 h after amygdaloid stimulation-induced seizures. A moderate increase in secretogranin II mRNA (144 ± 11% of contralateral side, P < 0.01) was found in the underlying cerebral cortex 2.5 h after unilateral craniotomy. These results indicate that measurement of changes in chromogranin mRNA, particularly secretogranin II, is a useful means of assessing both rapid and long-lasting increases and decreases in neuronal activity and, in contrast to immediate early gene mRNA levels, may better reflect specific changes in neuronal secretory activity associated with transmitter/peptide release.

Ancillary