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PubMed2004

Novel analogs of choline as potential neuroprotective agents.

The ability of choline to serve as a full, though low potency agonist for the alpha7 nicotinic receptor has provided the impetus to develop analogs that exhibit levels of potency and effectiveness suitable for use as therapeutic agents. Seven analogs of choline were synthesized based on previous work with the analog pyrrolidinecholine. The drugs were administered to differentiated PC-12 cells 24 hr prior to growth factor withdrawal which itself induced cytotoxicity in 30-40% of the cells. Three of 7 choline analogs exhibited potency and efficacy similar to that for nicotine as cytoprotective agents. Despite being tertiary amines, 4 of the choline analogs were more potent than choline in inhibiting [(3)H]choline uptake into cultured fibroblasts transfected with the high affinity, sodium-dependent choline transporter. One of the most effective analogs JAY 2-21-29 was shown to produce a potent (EC50 approximately 30 nM) cytoprotective action that was blocked by pretreatment with the alpha7 nicotinic receptor selective antagonist methyllycaconitine, but not by thealpha2 subtype-preferring antagonist dihydro-beta-erythroidin. These preliminary studies support the further neurochemical characterization of these compounds 1) as selectivealpha7 nicotinic receptor agonists and, 2) based on their interaction with the choline transporter, as potential cholinergic false neurotransmitters as has been demonstrated for pyrrolidinecholine.

Aconitine↗
PubMed1984

Effects of supplemental methionine and potassium sulfate on the choline requirement of the turkey poult.

Two experiments were conducted to study the relationship of methionine and potassium sulfate (K2SO4) on the choline requirement of turkey poults from hatch to three weeks of age. A corn-soybean meal basal diet was used which contained no supplemental choline or methionine. Also sulfate-free trace minerals were used. In Experiment 1, a linear increase in body weight was obtained by adding supplemental choline up to 660 mg/kg when the diet did not contain supplemental methionine. No response was obtained from supplemental choline when the diet contained a level higher than required for methionine (.25%). Feed efficiency was not affected by supplemental choline regardless of the level of supplemental methionine. In Experiment 2, a linear response in body weight was obtained by adding supplemental choline up to 1100 mg/kg diet in the presence or absence of supplemental K2SO4. The addition of K2SO4 to the diet did not significantly increase body weight at any level of supplemental choline. However, when all levels of choline were combined, the addition of K2SO4 significantly increased body weight, which indicated that the response from the two supplements were additive.

Animals↗
PubMed1976

Drug-induced stimulation of transport of hydrolyzed nitrogen mustard and choline by normal and leukemic human cells in vitro.

The effect of morphine and cocaine on the transport of hydrolyzed nitrogen mustard (NH2-OH) and choline by peripheral blood cells of normal subjects and patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloblastic leukemia was determined. Transport of HN2-OH by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia was stimulated by morphine and cocaine and, in each case, the effect was statistically significant (P less than 0.05 or greater). However, choline transport by normal lymphocytes was not altered by cocaine and was only slightly stimulated by morphine; choline transport by lymphocytes from patients with chronic lymphocytic leukemia was not stimulated by either morphine or cocaine. HN2-OH and choline transport by cells from patients with either acute lymphoblastic or myeloblastic leukemia was stimulated to a comparable degree by both drugs. Stimulation of HN2-OH transport by morphine and cocaine was greater in normal lymphocytes than in acute leukemic cells and the differences were highly significant (p less than 0.001). Conversely, stimulation of choline transport was more marked in acute leukemic cells than in normal lymphocytes, and these differences were also highly significant (p less than 0.001). It was previously shown that transport of nitrogen mustard by normal and leukemic human cells was biphasic in nature, consisting of a choline-independent component at "high" drug concentrations and a choline-dependent system at "low" substrate concentrations. The preferential stimulation of the low-dose, choline-dependent system by morphine and cocaine in acute leukemic cells relative to that observed in normal lymphocytes suggests a possible mechanism of increasing the therapeutic index of nitrogen mustard.

Biological Transport↗
PubMed2002

Choline ingestion does not modify physical or cognitive performance.

OBJECTIVES: This study was undertaken to determine whether choline ingestion improves physical and cognitive performance following exhaustive load carriage exercise. METHODS: In a double-blind crossover study, 13 men (28 +/- 2 years) underwent four test sessions: load carriage treadmill and no-load carriage test sessions after taking choline or placebo. Physical and cognitive performance batteries were administered at the end of the test sessions. RESULTS: Choline ingestion (50 mg/kg body weight) significantly (p < 0.05) increased plasma choline concentrations during the load and no-load carriage test sessions. However, plasma choline did not decrease during the placebo load carriage test session, an indication that load carriage does not deplete circulating choline. There were no differences in performance on physical tasks, and choline ingestion had no effect on reaction time, logical reasoning, vigilance, spatial memory, or working memory. CONCLUSION: In healthy men, supplemental choline did not affect physical or cognitive performance after exhaustive physical activity.

Adult↗
PubMed2003

Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET.

UNLABELLED: Prostate cancer is known for its difficulties in preoperative staging of pelvic lymph nodes by conventional imaging techniques. Thus, a histopathologic examination of the pelvic lymphadenectomy specimen is mandatory for patients at risk for metastatic disease. The aim of this study was to evaluate the strength and accuracy of (11)C-choline PET in preoperative noninvasive staging of pelvic lymph nodes in prostate cancer. METHODS: In a prospective study we examined 67 consecutive patients with histologically proven prostate cancer with (11)C-choline PET. The results of PET were compared with the results of histology of the pelvic lymph nodes and with the follow-up data. Conventional axial imaging was routinely performed using MRI or CT. The sensitivity, specificity, and accuracy of (11)C-choline PET were calculated. RESULTS: Fifteen patients had histologically proven lymph node metastases. (11)C-Choline PET was true-positive in 12 of 15 patients and false-negative in 3 patients. Fifty-two patients had no lymph node metastases. (11)C-Choline PET was true-negative in 50 of 52 patients and false-positive in 2 patients. We calculated a sensitivity of (11)C-choline PET for staging metastatic lymph node disease of 80%, a specificity of 96%, and an accuracy of 93%. Next, (11)C-choline PET detected solitary extraregional lymph node metastases in 5 of 12 patients with nodal metastases. CONCLUSION: This study showed that (11)C-choline PET is sensitive and accurate in preoperative staging of pelvic lymph nodes in prostate cancer.

Adenocarcinoma↗
PubMed1992

Molecular cloning, characterization, and expression in Escherichia coli of a cDNA encoding mammalian choline kinase.

A rat liver lambda gt11 cDNA library was screened with antibody against rat liver choline kinase. One of the putative phage clones obtained was found to express choline kinase activity in infected Escherichia coli cells and used for the isolation of fully extended cDNA clones by hybridization. The obtained clones had identical overlapping nucleotide sequences and gave a composite cDNA sequence of 2540 bases. Poly(A)+ tails were found at three different sites of the cDNA sequence. Within the sequence there was a large open reading frame encoding 435 amino acids with a molecular mass of 49,743 Da. When this open reading frame was placed after the trc promoter and introduced into E. coli cells, fully active choline kinase was produced. This enzyme was partially purified using a published choline kinase purification method and was found to mediate the phosphorylation of choline, N,N-dimethylethanolamine,N-monomethylethanolamine, and ethanolamine. Similar to the case with choline kinases from various sources, Km decreased as the number of N-methyl groups increased. The deduced amino acid sequence significantly resembled the yeast choline kinase sequence. It also showed local sequence similarity to protein kinases and some bacterial phosphotransferases. Northern blot analysis revealed that the cDNA probe hybridized to 2.8- and 1.8-kilobase RNA in various rat tissues. The sizes of the transcripts were fairly consistent with that of cDNA. The order of mRNA abundance was testis, brain, lung, kidney, and liver, but did not coincide with the order of the activity levels in these tissues. These results show that the cloned cDNA encodes one of the choline kinase isoforms present in mammalian tissues.

Amino Acid Sequence↗
PubMed2006

Value of 11C-choline PET and contrast-enhanced CT for staging of bladder cancer: correlation with histopathologic findings.

UNLABELLED: Lymph node involvement is a major prognostic factor in bladder cancer, but the accuracy of conventional imaging modalities for the prediction of regional and distant metastatic diseases is limited. This study was performed to compare the diagnostic accuracies of contrast-enhanced CT and PET with (11)C-choline for the staging of urothelial bladder cancer. METHODS: Twenty-seven patients (median age, 69.1 y) who had urothelial bladder cancer and who were referred for radical cystectomy and pelvic lymph node dissection (PLND) on the basis of a histologic evaluation after transurethral resection of bladder cancer (TURB) were studied. PET scanning, using 2 multiring whole-body tomographs, was performed 5 min after intravenous injection of approximately 370-500 MBq of (11)C-choline. In addition, conventional bone scintigraphy and contrast-enhanced CT were performed. After imaging, cystectomy and PLND were performed in all patients. Pathologic (11)C-choline uptake that could not be explained by intestinal activity was noted as a positive result. Node positivity was determined by size on CT: nodes measuring more than 1 cm in the long axis were described as being positive for tumor. Histopathologic findings were used as a reference. RESULTS: The presence of residual bladder cancer (pTa-pT4) was correctly detected in 21 of 25 histologically tumor-positive patients (84%) by CT and in 24 of 25 patients (96%) by (11)C-choline PET. Lymph node involvement was correctly detected in 4 of 8 patients (50%) by CT and in 5 of 8 patients (62%) by (11)C-choline PET. The median size of the 3 nodes with false-negative PET results was 9 mm (range, 6-21 mm), and the median size of the metastatic lesions within the lymph nodes was 3 mm (range, 1-15 mm). CT resulted in 6 (22%) false-positive lymph nodes, whereas none was demonstrated by (11)C-choline PET; these data indicated a significantly higher accuracy of PET than of CT (P < 0.01). Both modalities missed a small peritoneal metastasis verified by histologic evaluation. No positive results were obtained from bone scintigraphy. CONCLUSION: These preliminary data suggest that (11)C-choline PET is comparable to CT for detecting residual bladder cancer after TURB but appears to be superior to CT for the evaluation of potential additional lymph node metastases. (11)C-choline PET should be further evaluated for staging in patients who have bladder cancer and who are scheduled for radical cystectomy.

Aged↗
PubMed2006

Ocular lesions and experimental choline deficiency.

Previous studies have shown ocular haemorrhages in choline-deficient rats. The aim of this paper is to study further the relationship between ocular and renal lesions and biochemical alterations in rats fed a choline-deficient diet. Fifty one weanling male Wistar rats, were divided into two groups. Thirty one of them were fed a choline-deficient diet and the rest was fed a choline-supplemented diet ad libitum. Animals from both groups were killed between the fifth and the eighth day. Urea, creatinine and homocysteine concentrations in blood were determined. Eyes were used for light microscopy study; high resolution light microscopy and the study of the retina as "rétine a plat". Kidneys were studied by light microscopy. Choline-supplemented rats did not show ocular or renal lesion. Choline-deficient rats that showed renal lesions, tubular or cortical necrosis, did not always have ocular changes. There were no ocular changes in the only choline-deficient rat without renal lesion. The ocular changes consisted mainly in haemorrhage in both cameras and ciliary and vitreous bodies. Correlations between ocular and renal lesion (r = 0.72, p < 0.0001, CI 95%: 0.48-0.86); ocular lesion and creatinine (r = 0.86, p < 0.0001, Cl 95%: 0.72-0.93) and ocular lesion and urea (r = 0.70, p < 0.0001, Cl 95%: 0.44-0.85) were positive. Choline-deficiency induces ocular haemorrhagic lesions after the development of renal necrosis. The ocular pathology could be due to the immaturity of the ocular vasculature at this age. The hyaloid, choroid and retinal system are involved.

Analysis of Variance↗
PubMed1989

Cloning and characterization of the yeast CKI gene encoding choline kinase and its expression in Escherichia coli.

Using a mutant defective in choline kinase (Hosaka, K., and Yamashita, S. (1980) J. Bacteriol. 143, 176-181; Hosaka, K., and Yamashita, S. (1987) Eur. J. Biochem. 162, 7-13), the structural gene (CKI) for choline kinase of the yeast, Saccharomyces cerevisiae, was isolated by means of genetic complementation. Within its sequence there was an open reading frame capable of encoding 582 amino acids with a calculated molecular weight of 66,316. The primary translation product contained a segment closely related to the phosphotransferase consensus sequence (Brenner, S. (1987) Nature 329, 21). A yeast transformant carrying CKI in multiple copies exhibited very high choline kinase activity as well as ethanolamine kinase activity. In-frame insertion of the CKI coding frame into lacZ' on the pUC19 vector led to efficient expression of choline kinase in Escherichia coli cells in the presence of a lac inducer, isopropylthiogalactoside, proving that CKI is the structural gene for choline kinase. Concomitantly, ethanolamine kinase activity was also expressed. When the CKI locus in the wild-type yeast genome was inactivated by its replacement with the in vitro disrupted cki gene, the yeast cells lost virtually all of the choline kinase activity and most of the ethanolamine kinase activity. Thus, it is concluded that choline kinase is mono-cistronic and that the ethanolamine kinase activity is a second activity of choline kinase in the yeast.

Amino Acid Sequence↗
PubMed1985

Hepatocarcinogenic and promoting action of a choline-devoid diet in the rat.

Male Fisher 344 rats were solely fed a choline-supplemented diet for 65 to 105 weeks or a choline-devoid diet for 24 to 102 weeks. Hepatocellular carcinomas developed in the latter animals, beginning at 24 weeks. Other groups of rats were given a single dose of 20 mg diethylnitrosamine/kg, 18 h after a partial hepatectomy and were fed, 4 weeks thereafter, either a choline-supplemented, or a choline-devoid diet for up to 48 weeks. In rats fed the choline-supplemented diet, the only relevant lesion observed was a small transect number of foci of enzyme-altered hepatocytes. On the other hand, a significant number of foci, of preneoplastic nodules, and of hepatocellular tumors developed in rats fed the choline-devoid diet. The results obtained are consistent with those previously reported by others, indicating that diets devoid of choline, or of choline and methionine, are carcinogenic. The diets appear to act as complete carcinogens, since they are also efficient promoters of chemical hepatocarcinogenesis, as shown again, in the present study, by the results obtained in the diethylnitrosamine-pretreated rats.

Animals↗
PubMed1986

Modifications in choline transport activity as a function of membrane potential and the sodium gradient.

Advantage was taken of a preparation of proteoliposomes made using Torpedo presynaptic membranes in which both the internal and external media can be controlled to investigate the effects of membrane potential and the Na+ gradient on choline transport activity. Under control conditions, Na+ outside and K+ inside, choline was concentrated by proteoliposomes and this phenomenon was sensitive to hemicholinium-3 and high levels of external choline. While proteoliposomes showed no permeability towards K+ spontaneously, in the presence of valinomycin a transmembrane potential was developed. The rate of transport was higher, the greater the inside negative potential. Both the affinity and the maximal velocity of high affinity transport rose in the presence of a potential. Likewise, the affinity and velocity of this transporter increased with increasing external Na+. Increasing internal Na+, on the other hand, caused a decrease in affinity and had little effect on the maximal velocity. The low affinity component was much less, if at all, affected by these changes. These results are consistent with a model of high affinity choline transport in which Na+ binds before choline and the carrier-Na+-choline complex is positively charged. However, these results do not provide a direct explanation for choline transport activation by nerve activity, underlining the need to study the effects of parameters other than membrane potential and the Na+ gradient on choline transport activity.

Animals↗
PubMed1982

Monoclonal antibodies selective for Drosophila melanogaster choline acetyltransferase.

The newly developed monoclonal antibody technology was applied to the production of antibodies selective for Drosophila melanogaster choline acetyltransferase (EC 2.3.1.6). Two stable cell lines, 1C8 and 1G4, were isolated from NS-1/spleen cell hybrids by employing a choline acetyltransferase enzyme activity-screening method. Both cell lines were cloned twice and were maintained in continuous culture and as ascites tumors. Purified antibody was isolated from ascites fluids by pH elution after adsorption to Protein A-Sepharose. Both antibodies eluted from the Protein A-Sepharose as a single subclass, IgG1, and directly inhibited choline acetyltransferase activity. Scatchard analysis of titration data for choline acetyltransferase antibody-enzyme interaction generated linear curves for both antibodies: KA for 1C8 was 2.77 X 10(7) M-1 and KA for 1G4 was 0.78 X 10(7) M-1. Inclusion of the choline acetyltransferase substrate acetyl-CoA at 10 times the KM in the antibody-enzyme reaction mixture substantially reduced the level of inhibition observed with both antibodies; choline, however, exhibited no protective effect. Neither antibody reacted with choline acetyltransferase-containing extracts of vertebrates or other insect neural tissues. We conclude that the two antibodies are nonidentical, monoclonal, and highly selective for D. melanogaster choline acetyltransferase, both reacting at or near the acetyl-CoA binding region of the enzyme-active site.

Animals↗
PubMed1983

Mobilization of cellular choline by stimulation of muscarine receptors in isolated chicken heart and rat cortex in vivo.

The effects of cholinesterase inhibitors and muscarinic agonists on efflux of choline were studied in isolated perfused chicken heart and rat cortex in vivo. In the heart, the phospholipase A2 inhibitor mepacrine (10(-4) M) reduced the choline efflux (1.1 nmol g-1 min-1) by 51 +/- 5% (N = 3), whereas several cholinesterase inhibitors (physostigmine, neostigmine and diisopropylfluorophosphate) and muscarinic agonists (acetylcholine, oxotremorine and bethanechol) caused an increase. The muscarinic increase in choline efflux appears to be specific, as the increase caused by 10(-6) M physostigmine (+113%), by 3 X 10(-7) M acetylcholine (+89%) or by 5 X 10(-4) M bethanechol (+29%) was blocked by atropine. Cholinesterase inhibitors and muscarinic agonists also caused a decrease in heart rate by about 50%. Papaverine (10(-5) M) blocked the physostigmine- or bethanechol-evoked increase in choline efflux, but left the decrease in heart rate unchanged. Choline efflux from rat cortex in vivo was studied using the "cup technique." During the experimental period (3 hr), resting efflux declined from 60 to 15 pmol cm-2 min-1. Again choline efflux was increased by physostigmine (+48%) or by bethanechol (+48%) added to the cup solution from 80 to 160 min, whereas a decrease was observed after atropine plus physostigmine (-36%) or atropine plus bethanechol (-26%). In conclusion, stimulation of muscarine receptors increased extracellular choline by mobilization of cellular choline presumably through an effect on phospholipid metabolism. The hypothesis is discussed that synthesis of acetylcholine in the brain may be supported by an autoregulation of precursor availability.

Acetylcholine↗
PubMed1993

Choline incorporation into phospholipids in mesothelial cells in vitro.

OBJECTIVE: To determine the effect of extracellular choline concentration on phospholipid production and handling by peritoneal mesothelial cells in vitro. DESIGN AND MEASUREMENTS: Radiolabeled choline was used to monitor the formation of phosphatidylcholine (PC), sphingomyelin (SPH), and lysophosphatidylcholine (LPC) by rat and rabbit mesothelial cells as a function of concentration and time of exposure to choline. The subcellular location of the newly formed phospholipids was examined by ultracentrifugation in Percoll-sucrose gradients using analytical cell fractionation techniques. The fatty acid composition of the PC formed was determined by thin-layer chromatography (TLC) and gas chromatography. RESULTS: Choline incorporation into PC, SPH, and LPC increased with extracellular choline levels up to 640 mumol/L, which is 100 times greater than physiological levels of choline in plasma and 20 times higher than choline levels measured in peritoneal dialysis effluent. The newly formed, radiolabeled phospholipids were primarily found in a single subcellular compartment that exhibited a buoyant density of 1.05 g/mL in Percoll-sucrose gradients. Analysis of the fatty acyl groups of PC obtained from the mesothelial cells showed enrichment in palmitic [16:0], oleic [18:1], and linoleic [18:2] acids. CONCLUSION: The rate of phospholipid formation by mesothelial cells in vitro can be manipulated, in part, by choline concentration.

Animals↗
PubMed1998

PET imaging of prostate cancer using carbon-11-choline.

UNLABELLED: Prostate cancer is difficult to visualize using current techniques. Recently, 31P magnetic resonance spectroscopy has revealed that the tumor, in general, is characterized by an increased uptake of choline into the cell to meet increased synthesis of phosphatidylcholine, an important cell membrane phospholipid. We succeeded in using 11C-choline to visualize prostate cancer and its local metastasis in PET. METHODS: PET was performed on 10 prostate cancer patients from the level of pelvis to the lower abdomen. After transmission scanning, 370 MBq 11C-choline were injected intravenously. The emission scan was performed 5-15 min postinjection. Finally, PET images were displayed so that each pixel was painted by a specified color representing the degree of the standardized uptake value (SUV). The 11C-choline image was compared with the 18F-fluorodeoxyglucose (FDG) image obtained from the same patient. RESULTS: Imaging of prostate cancer and its local metastasis was difficult when 18F-FDG was used because, within the pelvis, the areas of high uptake were concealed by the overwhelmingly abundant radioactivity in urine (in ureters and bladder). By contrast, it was easy when 11C-choline was used because the urinary activity was negligible and tumor uptake was marked. The radioactivity concentration of 11C-choline in prostate cancer and metastatic sites was at an SUV of more than three in most cases. The SUV of 18F-FDG was considerably lower than that of 11C-choline. CONCLUSION: Prostate cancer and its local metastasis were visualized clearly in PET using 11C-choline.

Adenocarcinoma↗
PubMed2004

A CDP-choline pathway for phosphatidylcholine biosynthesis in Treponema denticola.

The genomes of Treponema denticola and Treponema pallidum contain a gene, licCA, which is predicted to encode a fusion protein containing choline kinase and CTP:phosphocholine cytidylyltransferase activities. Because both organisms have been reported to contain phosphatidylcholine, this raises the possibility that they use a CDP-choline pathway for the biosynthesis of phosphatidylcholine. This report shows that phosphatidylcholine is a major phospholipid in T. denticola, accounting for 35-40% of total phospholipid. This organism readily incorporated [14C]choline into phosphatidylcholine, indicating the presence of a choline-dependent biosynthetic pathway. The licCA gene was cloned, and recombinant LicCA had choline kinase and CTP:phosphocholine cytidylyltransferase activity. The licCA gene was disrupted in T. denticola by erythromycin cassette mutagenesis, resulting in a viable mutant. This disruption completely blocked incorporation of either [14C]choline or 32Pi into phosphatidylcholine. The rate of production of another phospholipid in T. denticola, phosphatidylethanolamine, was elevated considerably in the licCA mutant, suggesting that the elevated level of this lipid compensated for the loss of phosphatidylcholine in the membranes. Thus it appears that T. denticola does contain a licCA-dependent CDP-choline pathway for phosphatidylcholine biosynthesis.

Amino Acid Sequence↗
PubMed1998

Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats.

The effects of choline supplementation during two time-frames of early development on radial-arm maze performance and the morphology of basal forebrain neurons immunoreactive for the P75 neurotrophin receptor (NTR) in male and female Sprague-Dawley rats were examined. In the first experiment, rats were supplemented with choline chloride from conception until weaning. At 80 days of age, subjects were trained once a day on a 12-arm radial maze for 30 days. Compared to control littermates, supplemented rats made fewer working and reference memory errors; however, the memory enhancing effects of choline supplementation were greater in males than females. A morphometric analysis of NTR-immunoreactive cell bodies at three levels through the medial septum/diagonal band (MS/DBv) of these rats revealed that perinatal choline supplementation caused the somata of cells in the MS/DBv to be larger by 8-15%. In a second experiment, choline supplementation was restricted to embryonic days 12-17. A developmental profile of NTR immunoreactive cell bodies in the MS/DBv of 0-, 8-, 16-, 30- and 90-day old male and female rats again revealed that cell bodies were larger in choline-supplemented rats than controls. As in the behavioral studies, the effect of choline supplementation was greater in male than female rats. These data are consistent with the hypothesis that supplementation with choline chloride during early development leads to an increase in the size of cell bodies of NTR-immunoreactive cells in the basal forebrain and that this change may contribute to long-term improvement in spatial memory.

Animals↗
PubMed1997

Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats.

Rats were trained at 2-4 months and at 24-26 months of age on a peak-interval timing procedure in which auditory and visual stimuli signaled two different fixed-interval schedules of reinforcement (15 and 30 s) that were presented simultaneously in a hierarchical fashion. Compared with control rats, increases in the probability of attention to the 15 s signal were observed for both the choline-supplemented and the choline-deficient rats. In contrast, an increase in attention to the 30 s signal was only observed for the choline-supplemented rats, whereas choline-deficient rats exhibited a decrease in attention that increased with age. Proportional rightward shifts in the remembered times of reinforcement emerged for the 24-26-month-old rats in the choline-deficient and control groups, but not in the choline-supplemented group. These results indicate that prenatal choline supplementation facilitates cognitive function across the lifespan, whereas prenatal choline deficiency impairs divided attention and accelerates age-related declines in temporal processing.

Acoustic Stimulation↗