Skip to main content
Log in

Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia

  • Biological Psychiatry
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Changes in G-protein linked neurotransmitter receptors have been reported in a number of regions of the brain of schizophrenic subjects. These changes, if functional, could cause a change in proteins such as protein kinase C (PKC) and adenylate cyclase (AC) which are important components of the G-protein linked second messenger cascades. We therefore used autoradiography to measure the distribution and density of [3H]phorbol ester binding to PKC and [3H]forskolin binding to AC in tissue obtained at autopsy from schizophrenic and non-schizophrenic subjects (Controls). There were significant decreases in the density of PKC in the parahippocampal gyrus (687 ± 60 vs. 885 ± 51fmol/mg TE; mean ± SEM; p < 0.01) and in AC in the dentate gyrus (75 ± 4.9 vs. 92 ± 6.5, p < 0.05) from the schizophrenic subjects. These data could indicate that changes in neurotransmitter receptors in the hippocampus from subjects with schizophrenia could have resulted in a change in their associated second messenger systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Altshuler LL, Casanova MF, Goldberg TE, Kleinman JE (1990) The hippocampus and parahippocampus in schizophrenic, suicide and control brains. Arch Gen Psychiatry 47: 1029–1034

    Google Scholar 

  • American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, rev. American Psychiatric Association, Washington DC

    Google Scholar 

  • Appel NM, Robbins JD, De Souza EB, Seamon KB (1992) [125I]-labelled forskolin analogs which discriminate adenlyl cyclase and a glucose transporter: pharmacological characterization of binding sites in rat brain by in vitro receptor autoradiography. J Pharmacol Exp Ther 263: 1415–1423

    Google Scholar 

  • Arnold SE, Franz BR, Gur RC, Gur RE, Shapiro RM, Moberg PJ, Trojanowski JQ (1995) Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions. Am J Psychiatry 152: 738–748

    Google Scholar 

  • Arora RC, Meltzer HY (1991) Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients. J Neural Transm [Gen Sect] 85: 19–29

    Google Scholar 

  • Conrad AJ, Abede T, Austin R, Forsythe S, Scheibel AB (1991) Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Arch Gen Psychiatry 48: 413–417

    Google Scholar 

  • Dean B, Hayes W (1996) Decreased frontal cortical serotonin2Areceptors in subjects with schizophrenia. Schizophr Res 21: 133–139

    Google Scholar 

  • Dean B, Opeskin K, Pavey G, Naylor L, Hill C, Keks NA, Copolov DL (1995) [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. J Neurochem 64: 1197–1202

    Google Scholar 

  • Freedman R, Hall M, Adler LE, Leonard S (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 38: 22–33

    Google Scholar 

  • Gehlert D, Dawson T, Yamamura H, Wamsley J (1985) Quantitative autoradiography of [3H]Forskolin binding sites in the rat brain. Brain Res 361: 351–360

    Google Scholar 

  • Giambalvo CT, Wagner RL (1994) Activation of D1 and D2 dopamine receptors inhibits protein kinase C activity in striatal synaptoneurosomes. J Neurochem 63: 169–176

    Google Scholar 

  • Glatt CE, Snyder SH (1993) Cloning and expression of an adenylyl cyclase localized to the corpus striatum. Nature 361: 536–538

    Google Scholar 

  • Hashimoto T, Kitamura N, Kajimoto Y, Shirai Y, Shirakawa O, Mita T, Nishino N, Tanaka C (1993) Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia. Psychopharmacology (Berl) 112: S35-S39

    Google Scholar 

  • Heckers S, Heinsen H, Beckmann H (1991) Hippocampal neuron number in schizophrenia. Arch Gen Psychiatry 48: 1002–1008

    Google Scholar 

  • Hill C, Keks NA, Roberts S, Opeskin K, Dean B, Copolov DL (1996) Postmortem brain studies in schizophrenia: the problems of diagnosis. Am J Psychiatry 153: 533–537

    Google Scholar 

  • Horsburgh K, Dewar D, Graham DI, McCulloch J (1991) Autoradiographic imaging of [3H]phorbol 12,13-dibutyrate binding to protein kinase C in Alzheimers disease. J Neurochem 56: 1121–1129

    Google Scholar 

  • Jeste DV, Lohr JB (1989) Hippocampal pathologic findings in schizophrenia. Arch Gen Psychiatry 46: 1019–1024

    Google Scholar 

  • Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE (1993) Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 8: 315–336

    Google Scholar 

  • Julius D (1991) Molecular biology of serotonin receptors. Ann Rev Neurosci 14: 335–360

    Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96

    Google Scholar 

  • Kerwin RW, Beats BC (1990) Increased forskolin binding in the left parahippocampal gyrus and CA1 region in post mortem schizophrenic brain determined by quantitative autoradiography. Neurosci Lett 118: 164–168

    Google Scholar 

  • Kerwin RW, Patel S, Meldrum BS, Czudek C, Reynolds GP (1988) Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia. Lancet i: 583–584

    Google Scholar 

  • Kikkawa U, Nishizuka Y (1986) The role of protein kinase C in transmembrane signalling. Annu Rev Cell Biol 2: 149–178

    Google Scholar 

  • Luchins DJ (1990) A possible role of hippocampal dysfunction in schizophrenic symptomatology. Biol Psychiatry 28: 87–91

    Google Scholar 

  • Nishino N, Kitamura N, Hashimoto T, Kajimoto Y, Shirai Y, Murakami N, Nakai T, Komure O, Shirakaea O, Mita T, Nakai H (1993) Increase in [3H]cAMP binding sites and decrease in Gia and Goa immunoreactivities in left temporal cortices from patients with schizophrenia. Brain Res 615: 41–49

    Google Scholar 

  • Nishizuka Y (1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334: 661–665

    Google Scholar 

  • Opeskin K, Dean B, Pavey G, Hill C, Keks NA, Copolov DL (1996) Neither levels of protein kinase C nor adenylate cyclase are altered in the caudate putamen from subjects with schizophrenia. Schizophr Res 22: 159–164

    Google Scholar 

  • Pantelis C, Barnes TRE, Nelson HE (1992) Is the concept of frontal-subcortical dementia relevant to schizophrenia. Br J Psychiatry 160: 442–460

    Google Scholar 

  • Pearce RKB, Seeman P, Jellinger K, Tourtellotte WW (1990) Dopamine uptake sites and dopamine receptors in Parkinson's disease and schizophrenia. Eur Neurol 30 [Suppl 1]: 9–14

    Google Scholar 

  • Reynolds GP, Czudek C, Andrews HB (1990) Deficit and hemispheric asymmetry of GABA uptake sites in hippocampus in schizophrenia. Biol Psychiatry 27: 1038–1044

    Google Scholar 

  • Rolls ET, O'Mara S (1993) Neurophysiological and theoretical analysis of how the primate hippocampus functions in memory. In: Ono T, Squire LR, Raichle ME, Perrett DI, Fukuda M (eds) Brain mechanisms of perception and memory: from neuron to behaviour. Oxford University Press, New York, pp 276–300

    Google Scholar 

  • Sibley DR, Monsma FJ (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13: 61–69

    Google Scholar 

  • Sujzuki T (1993) Characterisation of protein kinase C activities in postsynaptic density fractions prepared from cerebral cortex, hippocampus and cerebellum. Brain Res 619: 69–75

    Google Scholar 

  • Wan DC, Pavey G, Dean B, Copolov DL (1996) Chronic treatment with haloperidol or clozapine causes differential changes in dopamine receptors but not levels of adenylate cyclase or protein kinase in rat forebrain. Life Sci 59: 2001–2008

    Google Scholar 

  • Weinberger DR, Berman KF, Zec RF (1986) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. Arch Gen Psychiatry 43: 114–124

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dean, B., Opeskin, K., Pavey, G. et al. Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia. J. Neural Transmission 104, 1371–1381 (1997). https://doi.org/10.1007/BF01294738

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01294738

Keywords

Navigation