Down-regulation of amygdala preprotachykinin A mRNA but not 3H-SP receptor binding sites in subjects affected by mood disorders and schizophrenia
- PMID: 15845098
- DOI: 10.1111/j.1460-9568.2005.04002.x
Down-regulation of amygdala preprotachykinin A mRNA but not 3H-SP receptor binding sites in subjects affected by mood disorders and schizophrenia
Abstract
Increasing evidence suggests that substance P (SP) neurokinin-1 (NK1) receptors are involved in stress and emotional responses, representing a potential _target for the treatment of anxiety and depression in humans. Given the important role of the amygdaloid complex in the regulation of emotional behavior, we examined the mRNA levels of preprotachykinin A [PPT-A, a precursor of both SP and neurokinin A (NKA)] and 3H-SP binding sites in the amygdala of patients affected by bipolar disorder, major depression or schizophrenia as compared with matched control individuals. By means of in situ hybridization, a significant reduction of PPT-A mRNA expression levels was detected in the three diagnostic groups, mainly in the basal, lateral and accessory basal amygdaloid nuclei, but not in the temporal cortical area proximal to the amygdala. Receptor autoradiography performed on adjacent sections showed no change in 3H-SP binding sites as compared with controls. No significant correlation was found between levels of PPT-A mRNA expression or binding sites and subject age, gender, hemisphere side, cause of death or history of substance misuse (marijuana, alcohol, cocaine/amphetamine). An inverse relationship between PPT-A mRNA expression levels and lifetime antipsychotic treatment (Fluphenazine) in the schizophrenic and bipolar disorder groups was found. Post-mortem delay was also negatively correlated with NK1 binding sites. The results confirm an involvement of the tachykinins in psychiatric disorders, suggesting there is a generalized impairment of the SP system in the amygdala in mood disorders and schizophrenia rather than this being a disease-related phenomenon.
Similar articles
-
Altered neuropeptide Y and neurokinin messenger RNA expression and receptor binding in stress-sensitised rats.Brain Res. 2008 May 30;1212:35-47. doi: 10.1016/j.brainres.2008.03.018. Epub 2008 Mar 20. Brain Res. 2008. PMID: 18440496
-
Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid levels in the amygdala of patients with major mental illness.Biol Psychiatry. 2004 Dec 1;56(11):844-52. doi: 10.1016/j.biopsych.2004.09.006. Biol Psychiatry. 2004. PMID: 15576061
-
A role for tachykinins in female mouse and rat reproductive function.Biol Reprod. 2003 Sep;69(3):940-6. doi: 10.1095/biolreprod.103.017111. Epub 2003 May 28. Biol Reprod. 2003. PMID: 12773411
-
The role of substance P in stress and anxiety responses.Amino Acids. 2006 Oct;31(3):251-72. doi: 10.1007/s00726-006-0335-9. Epub 2006 Jul 6. Amino Acids. 2006. PMID: 16820980 Review.
-
Involvement of substance P and the NK-1 receptor in cancer progression.Peptides. 2013 Oct;48:1-9. doi: 10.1016/j.peptides.2013.07.024. Epub 2013 Aug 7. Peptides. 2013. PMID: 23933301 Review.
Cited by
-
Convergent Functional Genomics of bipolar disorder: from animal model pharmacogenomics to human genetics and biomarkers.Neurosci Biobehav Rev. 2007;31(6):897-903. doi: 10.1016/j.neubiorev.2007.05.008. Epub 2007 Jun 3. Neurosci Biobehav Rev. 2007. PMID: 17614132 Free PMC article. Review.
-
Deficits in substance P mRNA levels in the CeA are inversely associated with alcohol-motivated responding.Synapse. 2009 Nov;63(11):972-81. doi: 10.1002/syn.20677. Synapse. 2009. PMID: 19593822 Free PMC article.
-
Substance P enhances excitatory synaptic transmission on spinally projecting neurons in the rostral ventromedial medulla after inflammatory injury.J Neurophysiol. 2009 Aug;102(2):1139-51. doi: 10.1152/jn.91337.2008. Epub 2009 Jun 3. J Neurophysiol. 2009. PMID: 19494188 Free PMC article.
-
Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.Mol Psychiatry. 2016 Aug;21(8):1009-26. doi: 10.1038/mp.2016.90. Epub 2016 Jun 7. Mol Psychiatry. 2016. PMID: 27271499 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical