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Gene Review

CA3  -  carbonic anhydrase III

Homo sapiens

Synonyms: CA-III, CAIII, Car3, Carbonate dehydratase III, Carbonic anhydrase 3, ...
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Disease relevance of CA3


Psychiatry related information on CA3

  • Four out of five probands and the same eight controls had been examined in a previous study showing a significantly lower cell count and disorientation of pyramidal cells in the CA1- CA3 subregions of the schizophrenics [6].
  • By contrast, in morphometric analyses of Alzheimer's disease brains, 80-93% of pyramidal cells in the prefrontal cortex (laminae III or V) and hippocampus (CA2, CA3) displayed two- to eightfold higher numbers of hydrolase-positive vacuolar compartments than did corresponding cell populations in age-matched normal brains [7].
  • The CA3 subregion of the hippocampus supports processes associated with spatial pattern association, spatial pattern completion, novelty detection, and short-term memory [8].
  • Moreover, reversal training selectively affects hippocampal CA3 and CA1 regions, suggesting a specific function of these hippocampal subregions in reversal learning [9].
  • The aim of the present study was to investigate whether functional changes at CA3-CA1 synapses in the hippocampus could underlie learning and memory deficits produced in rat offspring by a prenatal exposure model simulating the carbon monoxide (CO) exposure observed in human cigarette smokers [10].

High impact information on CA3

  • Field potentials and intracellular recordings observed during interictal spikes of penicillin-treated slices of the hippocampus were reproduced by a mathematical model of a network of 100 hippocampal neurons from the region including CA2 and CA3 [11].
  • We report the isolation and analysis of genomic clones comprising the entire gene coding for the human muscle carbonic anhydrase, CAIII [12].
  • However DNA from differentiated type II adult muscle fibers is undermethylated at these sites even though CAIII is not expressed [12].
  • Methylation studies suggest that some CCGG sites clustered in the CpG-rich island are undermethylated in DNA from fetal and adult muscle and in other tissues irrespective of CAIII expression [12].
  • The key point of the model is that small concurrent changes during aging strengthen the auto-associative network of the CA3 subregion at the cost of processing new information coming in from the entorhinal cortex [13].

Chemical compound and disease context of CA3


Biological context of CA3

  • Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci [19].
  • By 32-34 weeks gestational age, neurons in CA2 and CA3 have undergone rapid enlargement and morphologic maturation, surpassing CA1, which still contains some immature neurons [20].
  • To investigate, we tested the hypothesis that selective vulnerability in human hippocampus is related to regional differences in neuronal cell death and cell receptor gene expression in CA1 vs. CA3 subregions [21].
  • Linkage analysis using the CEPH family DNA panel indicates a close genetic linkage between D8S8 and CA3, with a lod score of +7.80 at theta = 0.05 in males [22].
  • In situ hybridization data demonstrates that both CA1 and CA3 map to the same region (q13-q22) of chromosome 8 [23].

Anatomical context of CA3

  • The in situ hybridization analysis revealed that the expression of HCNP-pp mRNA in patients with clinically late-onset AD was decreased in the hippocampal CA1 field, but not in the CA3 field or the dentate gyrus [24].
  • We recently demonstrated statistically significant correlations between presurgical memory impairment and hippocampal volumetric cell densities (in CA3 and the hilar area only) for patients with idiopathic left temporal lobe epilepsy who exhibited marked hippocampal neuron loss [25].
  • Medium and late afterhyperpolarizations in CA3 pyramidal cells were larger in mice expressing either mutant form compared with WT and nontransgenic controls [26].
  • In normal controls, both the numerical and length density of IR dendrites were much higher in sector CA2 than in sectors CA3 or CA1 [27].
  • Within resistant sectors, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular layer of the dentate gyrus and in the stratum lucidum of CA3 (i.e., the termination zones of perforant pathway and mossy fibers) [28].

Associations of CA3 with chemical compounds


Physical interactions of CA3


Regulatory relationships of CA3


Other interactions of CA3

  • It includes an 18-amino acid signal sequence, a 260-amino acid region that shows 30-36% similarity with the 29-kDa cytoplasmic CAs (CA I, CA II, and CA III), and an additional 27-amino acid C-terminal sequence that ends in a 21-amino acid hydrophobic domain [40].
  • Although decreased GABA(A) receptor subunit staining, reflecting cell loss, was observed in CA1, CA3, and hilus, the distinct neuron-specific expression pattern of the alpha-subunit variants observed in controls was markedly changed in surviving neurons [41].
  • There was loss of neurons from within a predefined volume of brain tissue in sub-fields CA1, CA3, and CA4 one week or less after injury [42].
  • Good correlations were obtained with the results of CA III RIA and a commercial myoglobin RIA kit [43].
  • GFAP was increased by more than 50-fold, specifically within the neuropil of CA1-CA3, and by twofold in portions of fimbria [44].

Analytical, diagnostic and therapeutic context of CA3


  1. Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy. Van Paesschen, W., Revesz, T., Duncan, J.S., King, M.D., Connelly, A. Ann. Neurol. (1997) [Pubmed]
  2. Hippocampal cell loss in posttraumatic human epilepsy. Swartz, B.E., Houser, C.R., Tomiyasu, U., Walsh, G.O., DeSalles, A., Rich, J.R., Delgado-Escueta, A. Epilepsia (2006) [Pubmed]
  3. Excitotoxicity and epileptic brain damage. Meldrum, B. Epilepsy Res. (1991) [Pubmed]
  4. Improved specificity of myoglobin plus carbonic anhydrase assay versus that of creatine kinase-MB for early diagnosis of acute myocardial infarction. Brogan, G.X., Vuori, J., Friedman, S., McCuskey, C.F., Thode, H.C., Vaananen, H.K., Cooling, D.S., Bock, J.L. Annals of emergency medicine. (1996) [Pubmed]
  5. Differential expression of carbonic anhydrase isoenzymes in various types of anemia. Kuo, W.H., Yang, S.F., Hsieh, Y.S., Tsai, C.S., Hwang, W.L., Chu, S.C. Clin. Chim. Acta (2005) [Pubmed]
  6. Pyramidal neuron size in the hippocampus of schizophrenics correlates with total cell count and degree of cell disarray. Jönsson, S.A., Luts, A., Guldberg-Kjaer, N., Ohman, R. European archives of psychiatry and clinical neuroscience. (1999) [Pubmed]
  7. Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease. Cataldo, A.M., Hamilton, D.J., Barnett, J.L., Paskevich, P.A., Nixon, R.A. J. Neurosci. (1996) [Pubmed]
  8. A behavioral assessment of hippocampal function based on a subregional analysis. Kesner, R.P., Lee, I., Gilbert, P. Reviews in the neurosciences. (2004) [Pubmed]
  9. Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task. Havekes, R., Nijholt, I.M., Luiten, P.G., Van der Zee, E.A. Learn. Mem. (2006) [Pubmed]
  10. Prenatal exposure to a low concentration of carbon monoxide disrupts hippocampal long-term potentiation in rat offspring. Mereu, G., Cammalleri, M., Fà, M., Francesconi, W., Saba, P., Tattoli, M., Trabace, L., Vaccari, A., Cuomo, V. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  11. Cellular mechanism of neuronal synchronization in epilepsy. Traub, R.D., Wong, R.K. Science (1982) [Pubmed]
  12. Human muscle carbonic anhydrase: gene structure and DNA methylation patterns in fetal and adult tissues. Lloyd, J., Brownson, C., Tweedie, S., Charlton, J., Edwards, Y.H. Genes Dev. (1987) [Pubmed]
  13. Neurocognitive aging: prior memories hinder new hippocampal encoding. Wilson, I.A., Gallagher, M., Eichenbaum, H., Tanila, H. Trends Neurosci. (2006) [Pubmed]
  14. Activation of mammalian skeletal-muscle carbonic anhydrase III by arginine modification. Tashian, R.E., Johansen, J.T., Christiansen, E., Chegwidden, W.R. Biosci. Rep. (1984) [Pubmed]
  15. Serum myoglobin/carbonic anhydrase III ratio as a marker of reperfusion after myocardial infarction. Vuotikka, P., Uusimaa, P., Niemelä, M., Väänänen, K., Vuori, J., Peuhkurinen, K. International journal of cardiology. (2003) [Pubmed]
  16. Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Wiard, R.P., Dickerson, M.C., Beek, O., Norton, R., Cooper, B.R. Stroke (1995) [Pubmed]
  17. Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: brain microdialysis study. Mitani, A., Andou, Y., Kataoka, K. Neuroscience (1992) [Pubmed]
  18. Transplacentally induced neuronal migration disorders: an animal model for the study of the epilepsies. Germano, I.M., Sperber, E.F. J. Neurosci. Res. (1998) [Pubmed]
  19. Verbal memory impairment correlates with hippocampal pyramidal cell density. Sass, K.J., Spencer, D.D., Kim, J.H., Westerveld, M., Novelly, R.A., Lencz, T. Neurology (1990) [Pubmed]
  20. Human fetal hippocampal development: I. Cytoarchitecture, myeloarchitecture, and neuronal morphologic features. Arnold, S.E., Trojanowski, J.Q. J. Comp. Neurol. (1996) [Pubmed]
  21. Gene expression profiles in microdissected neurons from human hippocampal subregions. Torres-Muñoz, J.E., Van Waveren, C., Keegan, M.G., Bookman, R.J., Petito, C.K. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  22. The polymorphic human DNA sequence D8S8 assigned to 8q13-21.1, close to the carbonic anhydrase gene cluster, by isotopic and nonisotopic in situ hybridization and by linkage analysis. Edwards, Y., Williams, S., West, L., Lipowicz, S., Sheer, D., Attwood, J., Spurr, N., Sarkar, R., Saha, N., Povey, S. Ann. Hum. Genet. (1990) [Pubmed]
  23. Regional localization of carbonic anhydrase genes CA1 and CA3 on human chromosome 8. Davis, M.B., West, L.F., Barlow, J.H., Butterworth, P.H., Lloyd, J.C., Edwards, Y.H. Somat. Cell Mol. Genet. (1987) [Pubmed]
  24. Decreased expression of hippocampal cholinergic neurostimulating peptide precursor protein mRNA in the hippocampus in Alzheimer disease. Maki, M., Matsukawa, N., Yuasa, H., Otsuka, Y., Yamamoto, T., Akatsu, H., Okamoto, T., Ueda, R., Ojika, K. J. Neuropathol. Exp. Neurol. (2002) [Pubmed]
  25. Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions. Sass, K.J., Buchanan, C.P., Kraemer, S., Westerveld, M., Kim, J.H., Spencer, D.D. Neurology (1995) [Pubmed]
  26. Functional phenotype in transgenic mice expressing mutant human presenilin-1. Barrow, P.A., Empson, R.M., Gladwell, S.J., Anderson, C.M., Killick, R., Yu, X., Jefferys, J.G., Duff, K. Neurobiol. Dis. (2000) [Pubmed]
  27. GluR5,6,7 subunit immunoreactivity on apical pyramidal cell dendrites in hippocampus of schizophrenics and manic depressives. Benes, F.M., Todtenkopf, M.S., Kostoulakos, P. Hippocampus. (2001) [Pubmed]
  28. AMPA-selective glutamate receptor subtype immunoreactivity in the hippocampal formation of patients with Alzheimer's disease. Ikonomovic, M.D., Sheffield, R., Armstrong, D.M. Hippocampus. (1995) [Pubmed]
  29. Reelin-expressing neurons in the postnatal and adult human hippocampal formation. Abraham, H., Meyer, G. Hippocampus. (2003) [Pubmed]
  30. The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure. Sass, K.J., Lencz, T., Westerveld, M., Novelly, R.A., Spencer, D.D., Kim, J.H. Arch. Neurol. (1991) [Pubmed]
  31. Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus. Vreugdenhil, E., Datson, N., Engels, B., de Jong, J., van Koningsbruggen, S., Schaaf, M., de Kloet, E.R. J. Neurobiol. (1999) [Pubmed]
  32. Changes in thyrotropin-releasing hormone levels in hippocampal subregions induced by a model of human temporal lobe epilepsy: effect of partial and complete kindling. Knoblach, S.M., Kubek, M.J. Neuroscience (1997) [Pubmed]
  33. Distribution of immunoreactive cholecystokinin in the human hippocampus. Lotstra, F., Vanderhaeghen, J.J. Peptides (1987) [Pubmed]
  34. Rapid potentiation of DNA binding activities of particular transcription factors with leucine-zipper motifs in discrete brain structures of the gerbil with transient forebrain ischemia. Yoneda, Y., Ogita, K., Inoue, K., Mitani, A., Zhang, L., Masuda, S., Higashihara, M., Kataoka, K. Brain Res. (1994) [Pubmed]
  35. Modeling goal-directed spatial navigation in the rat based on physiological data from the hippocampal formation. Koene, R.A., Gorchetchnikov, A., Cannon, R.C., Hasselmo, M.E. Neural networks : the official journal of the International Neural Network Society. (2003) [Pubmed]
  36. Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury. Poirier, J., Beffert, U., Dea, D., Alonso, R., O'Donnell, D., Boksa, P. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  37. Distribution of the 5-HT5A serotonin receptor mRNA in the human brain. Pasqualetti, M., Ori, M., Nardi, I., Castagna, M., Cassano, G.B., Marazziti, D. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  38. Interictal-ictal interactions and limbic seizure generation. Avoli, M., Barbarosie, M. Rev. Neurol. (Paris) (1999) [Pubmed]
  39. Neural (N-) cadherin, a synaptic adhesion molecule, is induced in hippocampal mossy fiber axonal sprouts by seizure. Shan, W., Yoshida, M., Wu, X.R., Huntley, G.W., Colman, D.R. J. Neurosci. Res. (2002) [Pubmed]
  40. Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes. Okuyama, T., Sato, S., Zhu, X.L., Waheed, A., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  41. Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy. Loup, F., Wieser, H.G., Yonekawa, Y., Aguzzi, A., Fritschy, J.M. J. Neurosci. (2000) [Pubmed]
  42. There is differential loss of pyramidal cells from the human hippocampus with survival after blunt head injury. Maxwell, W.L., Dhillon, K., Harper, L., Espin, J., MacIntosh, T.K., Smith, D.H., Graham, D.I. J. Neuropathol. Exp. Neurol. (2003) [Pubmed]
  43. Dual-label time-resolved fluoroimmunoassay for simultaneous detection of myoglobin and carbonic anhydrase III in serum. Vuori, J., Rasi, S., Takala, T., Väänänen, K. Clin. Chem. (1991) [Pubmed]
  44. Reversal of amyloid beta toxicity in Alzheimer's disease model Tg2576 by intraventricular antiamyloid beta antibody. Chauhan, N.B., Siegel, G.J. J. Neurosci. Res. (2002) [Pubmed]
  45. Imaging triiodothyronine binding kinetics in rat brain: a model for studies in human subjects. Greenberg, J.H., Reivich, M., Gordon, J.T., Schoenhoff, M.B., Patlak, C.S., Dratman, M.B. Synapse (2006) [Pubmed]
  46. Expression of carbonic anhydrase isozyme III in the ciliary processes and lens. Jampel, H.D., Chen, X., Chue, C., Zack, D.J. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
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