Increased levels of serotonin 2A receptors and serotonin transporter in the CNS of neuregulin 1 hypomorphic/mutant mice.
Changes in neuregulin 1 expression have been reported in the CNS from subjects with schizophrenia. As neuregulin 1 is important in cortical development we postulated that changes in neuregulin 1 expression may contribute towards changes in cholinergic, glutamatergic and serotonergic markers that are well documented in the CNS of subjects with that disorder. To begin to test this hypothesis, we used in situ radioligand binding to measure levels of muscarinic M1/M4 receptors, the kainate receptor, the NMDA receptor, the serotonin 2A receptor, the serotonin 1A receptor and the serotonin transporter in the CNS from heterozygous transmembrane domain neuregulin 1 mutant mice. The major outcomes from these studies was the demonstration of an overall increase in levels of the serotonin 2A receptor (F=11.3, d.f.=3,1,72, p=0.0012) and serotonin transporter (F=5.00, d.f.=1,3,72, p<0.05) in the mutant mice. Levels of the other receptors did not vary in the mutant mice compared to their wild type-like litter mates. These data are the first evidence to suggest that NRG1 gene expression may be involved in regulating the development of the serotonergic system in the mammalian CNS.
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Parkville, Victoria, Australia. anddali@unimelb.edu.au
Brian
B
Dean
Tim
T
Karl
Geoffrey
G
Pavey
Simone
S
Boer
Liesl
L
Duffy
Elizabeth
E
Scarr
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020890:Neuregulin-1 / Q000235:genetics*; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043588:Receptor, Muscarinic M4 / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
D020890:Neuregulin-1; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D050486:Serotonin Plasma Membrane Transport Proteins