Psychiatry related information on Hacu

• Systemic application of a low dose of physostigmine (100 microgram/kg i.p.) normalized all of the enhanced parameters in hAChE-Tg mice: spontaneous motor activity, hippocampal ACh efflux and hippocampal HACU, attributing these parameters to the hypocholinergic state due to excessive AChE activity [1].
• Since human neocortex has recently been shown to possess intrinsic cholinergic innervation, our results indicate that alterations in CHT1-mediated high affinity choline uptake in cortical neurons may contribute to Alzheimer's dementia [2].
• These results indicate that MKC-231 improved the AF64A-induced working memory deficit and hippocampal ACh depletion, probably by recovering reduced high-affinity choline uptake and ACh release [3].

High impact information on Hacu

• Regulation of acetylcholine synthesis: does cytoplasmic acetylcholine control high affinity choline uptake [4]?
• 4,4'-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system [5].
• Also, the high-affinity choline uptake (HACU) in hippocampal synaptosomes from awake hAChE-Tg mice was accelerated but was reduced by halothane anaesthesia [1].
• In addition, the choline acetyltransferase-positive clones showed higher densities of voltage-gated Na(+) channels and enhanced high-affinity choline uptake, suggesting the accomplishment of a more advanced differentiated neuronal phenotype [6].
• We subsequently used our cell culture uptake system to kinetically define in HepG2 cells a high affinity choline uptake process, which transports choline with a K(m) similar to that of mOct1/Slc22a1 protein [7].

Biological context of Hacu

• Identification of a locus on mouse chromosome 17 associated with high-affinity choline uptake using BXD recombinant inbred mice and quantitative trait loci analysis [8].
• These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse [8].
• Neurochemical analysis was performed using measures of the kinetics of sodium-dependent high-affinity choline uptake in samples of hippocampus from injected mice and their relevant controls in both quiet conditions and immediately following selective working memory testing in an 8-arm radial maze [9].
• N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EAA) were shown to be inhibitors of high affinity choline uptake in vitro (IC50 = 0.4 microM and 1.5 microM, respectively), and intraventricular administration showed that EAA was more selective in its inhibition of hippocampal choline uptake in vivo [10].

Anatomical context of Hacu

• QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01 [8].
• The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline [8].
• Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3NGF+ transplants, whereas no recovery was observed in 3T3NGF- transplanted animals [11].
• These results imply that the two anomers of sialylcholesterol may modulate the synaptic membrane machinery differently, that is, the alpha-anomer may activate voltage-dependent calcium channels and the beta-anomer may facilitate high-affinity choline uptake [12].

Associations of Hacu with chemical compounds

• Binding of tritiated hemicholinium-3, a blocker of the high-affinity choline uptake characteristic of active cholinergic terminals, was over twofold enhanced in the brain of transgenic mice [13].
• HACU was inhibited by those drugs that enhance GABA transmission [14].
• The convulsant 3-mercaptopropionic acid, which decreases GABA levels, stimulated HACU [14].
• In rat brain synaptosomes, hyperforin inhibited high-affinity choline uptake with an IC(50) of 8.5 microM, whereas low-affinity uptake was not affected [15].
• At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 microg/mice), a specific inhibitor of high-affinity choline uptake in brain cholinergic neurons, was given intracerebroventricularly immediately after [16].

Other interactions of Hacu

• Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1 [8].
• Chronic treatment caused decreases in high-affinity choline uptake and [3H]QNB binding 24 hr after the final injection without any changes in ACh content, AChE activity or ChAT activity [17].
• This study therefore compared choline acetyltransferase activity (as a structural marker) and sodium-dependent high affinity choline uptake (which reflects both ongoing cholinergic neuronal activity and structural integrity) in the hippocampus, cortex and straitum of male C57BL mice at 3-4, 10-12 or 28-32 months of age [18].
• We investigated the influence of the amyloid-beta-peptide(1-42) on hemicholinum-3-sensitive high-affinity choline uptake in NG108-15 cells [19].
• Cholinergic-specific gangliosides, Chol-1 alpha, were assumed to participate in the mechanism of high-affinity choline uptake [20].

Analytical, diagnostic and therapeutic context of Hacu

• After the completion of the retention test at each of the training-test interval that were studied, the HACU in the hippocampus of HC-3-treated mice was not significantly different from that of saline-injected (1 microl) control groups [21].
• Because de novo synthesis of acetylcholine (ACh) is dependent on sodium-dependent high-affinity choline uptake, we studied the effect of hyperforin on choline (Ch) uptake in vitro and on striatal ACh release in vivo using microdialysis [15].

References