Disease relevance of CA3

• Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus [1].
• PURPOSE: We performed this study to determine whether significant head trauma in human adults can result in hippocampal cell loss, particularly in hilar (polymorph) and CA3 neurons, similar to that observed in animal models of traumatic brain injury [2].
• Hippocampal lesions occurring acutely after status epilepticus show a high degree of selectivity for hilar interneurones, CA1 pyramidal neurones and CA3 pyramidal neurones [3].
• This study compared the clinical utility of serum myoglobin (S-Mgb) in conjunction with the ratio of S-Mgb to CA-III (S-Mgb/CA-III) versus creatine kinase-MB (CK-MB) for the early diagnosis of acute myocardial infarction (AMI) [4].
• Compared with controls, CAIII concentration was lower in iron deficiency anemia (P<0.01), but higher in beta-thalassemia anemia (P<0.001) [5].

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

• Purified carbonic anhydrase isozymes I, II, and III (CA I, CA II, CA III) from various sources were treated with 2,3-butanedione and their bicarbonate dehydration reactions followed [14].
• METHODS: We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty [15].
• Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus [16].
• Extracellular glutamate levels were significantly increased during ischemia in both field CA1 and field CA3 [17].
• In rats with severe NMD, kainic acid-induced status epilepticus produced hippocampal damage in the CA3/4 region [18].

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

• They are numerous in the strata lacunosum-moleculare and radiatum of CA1-CA3, in the hilus, and in the molecular layer of the dentate gyrus, but less common in stratum oriens and alveus, and rare in the principal cell layers [29].
• Intracarotid amobarbital procedure memory results were related to CA3 neuronal loss only [30].
• Northern blot analysis and in situ hybridization experiments showed that CARP mRNA is specifically induced by kainate-elicited seizures in the dentate gyrus and in the pyramidal layers CA1 and CA2, but not in CA3 [31].
• The thyrotropin-releasing hormone response was less robust in ventral hilus/CA4 and CA3 areas, leading to speculation that this smaller response could, in part, explain why the ventral (temporal) hippocampus may be more susceptible to seizure-induced damage [32].
• Those fibers are particularly abundant around pyramidal cells of the CA2 and CA3 subfields of the Ammon's horn and around granular cells suggesting synaptic interaction between the CCK nerve terminals and glutamate neurons of these two regions [33].

Physical interactions of CA3

• CAII provides the CA activity necessary for maintaining ion transport in erythrocytes while CAIII may play an agent against oxidative damage in iron deficiency and beta-thalassemia anemia [5].
• Among 3 different hippocampal subfields examined, the dentate gyrus had the highest basal DNA binding activities of AP1 with progressively less potent binding in the CA3 and CA1 subfields [34].

Regulatory relationships of CA3

• Together, input from ECIII and CA3 activated predictive spiking in cells in CA1 for the next desired place on a shortest path to a goal [35].
• In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss [36].
• In the hippocampus, the dentate gyrus and the pyramidal cell layer of the CA1 and CA3 fields expressed 5-HT5A mRNA at high levels [37].
• Hence, the functional integrity of hippocampal CA3 neurons may represent a critical control point in temporal lobe epilepsy [38].
• In pilocarpine-induced status epilepticus, the expression of N-cadherin mRNA was sharply upregulated and reached a maximum level (1- to 2.5-fold) at 1- to 4 weeks postseizure in the granule cell layer and the pyramidal cell layer of CA3 [39].

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

• Regional concentrations of label in autoradiograms were measured by densitometry in hippocampus (CA1, CA2, CA3, and dentate gyrus), cerebellum (molecular and granular cell layers), caudate nucleus, and amygdala [45].
• We used laser capture microdissection to remove approximately 600 CA1 and 600 CA3 pyramidal neurons each from five fresh-frozen normal post-mortem brains, extracted total RNA and double-amplified mRNA [21].
• Hippocampal lesions in anterior temporal lobectomy specimens tend to involve the subfields less selectively with CA1 being only slightly more severely affected than dentate granule cells, CA3 and CA2 pyramidal neurones [3].
• Using somatic cell genetic techniques we have mapped two of the CA genes (CA1 and CA3) to human chromosome 8 [23].
• The sequence of the PCR product from human lens was identical to the published sequence of the corresponding region of the human CA III gene [46].

References