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| Laura Caberlotto |
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GlaxoSmithkline - via Fleming, 4 - 37100 Verona
e-mail: Laura.L.Caberlotto@gsk.com |
Poster Presentation: |
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| THE DOWN-REGULATION OF PREPROTACHYKININ A mRNA IN THE AMYGDALA OF SUBJECTS AFFECTED BY MOOD DISORDERS AND SCHIZOPHRENIA DOES NOT REFLECT A CHANGE IN 3H-SP RECEPTOR BINDING SITES.. |
| L.Caberlotto, S. Melotto, M. Corsi, and R. Carletti | |
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Department of Biology, Psychiatry-CEDD, GlaxoSmithKline Medicine Research Centre, Verona, Italy. |
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| Substantial evidence indicates that the amygdala is a critical brain region for the regulation of affective behaviour and neurochemical responses to stress. The neuropeptide substance P (SP), acting preferentially via neurokinin-1 (NK1) receptors, is a member of the tachykinin family of peptides, which includes also neurokinin A and B. In recent years, it has attracted great interest for its suggested role in the pathophysiology of psychiatric disorders. The present study investigated the levels of preprotachykinin A mRNA (PPT-A; precursor of both SP and NKA) and 3H-SP binding sites in the amygdaloid complex of subjects affected by unipolar and bipolar depression as compared to matched controls (n=15/group). In addition, a group of subjects diagnosed with schizophrenia was also included in the study to assess potential disease-related changes. By means of in situ hybridization using a riboprobe specific for PPT-A, a significant difference (ANOVA p<0.039) in PPT-A mRNA expression levels was detected in the basal nucleus with controls being higher than major depression (Tukey Kramer post-hoc test, p = 0.012), bipolar disorders (p = 0.026), and schizophrenics (p = 0.011). Similar reduction was seen in the lateral nucleus (p = 0.027; post-hoc p = 0.007 major depression, p = 0.005 bipolar, p = 0.002 schizophrenics). Receptor autoradiography performed on adjacent sections showed no change in 3H-SP binding sites in any of the amygdaloid nuclei studied.
No significant correlation was found between the PPT-A mRNA expression or binding site levels and subject age, gender, hemisphere side, cause of death or history of substance abuse (marijuana, alcohol, cocaine/ amphetamine). However, an inverse relationship was found between PPT-A mRNA expression levels and lifetime antipsychotic treatment with Fluphenazine (lateral r = -0.34, p = 0.009; basal r = -0.34, p = 0.012; accessory basal r = -0.38, p = 0.005). According to the present results, the reduction of PPT-A mRNA suggests a generalized impairment of the tachykinin system in the amygdala in all psychiatric states. Future investigations are needed to assess the functional relationship between SP/NKA and NK1 receptors in pathological states. |
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