Biomedical subjects

T Ma

Publications and source records attributed to T Ma.

At least 73 records · Page 4Linked to original sources

PubMed1999

Region specific expression of NMDA receptor NR1 subunit mRNA in hypothalamus and pons following chronic morphine treatment.

The NMDA receptor has been implicated in opioid tolerance and physical dependence. Using in situ hybridization techniques, the effects of chronic morphine treatment on the expression of mRNAs encoding the NMDA receptor subunits NRI, NR2A, and NR2B were investigated. A significant increase in the level of the NR1 subunit mRNA was found in the locus coeruleus and the hypothalamic paraventricular nucleus following 3 days of intracerebroventricular (i.c.v.) morphine infusion (26 nmol microl(-1) h(-1)) through osmotic minipumps. No changes were detected in expression of the NRI mRNA in the frontal cortex, caudate-putamen, nucleus accumbens, amygdala, CA1, CA2, and the dentate gyrus of the hippocampus, and in the central grey after morphine treatment. The expression of NR2A and NR2B subunit mRNAs did not change after morphine treatment in any brain region. These results suggest that changes in gene expression of the NRI subunit of the NMDA receptor are involved in the development of morphine tolerance and dependence.

Analgesics, Opioid↗

PubMed1999

Effects of chemical disinfectants on surface characteristics and color of three fixed prosthodontic crown materials.

STATEMENT OF PROBLEM: Dental restorations should reproduce similar optical effects as natural tooth structure to achieve a good color match. Mismatch can result in unsatisfactory shade matching. PURPOSE: This study determined whether chemical disinfectants affected the surface texture and color of 3 fixed prosthodontic materials. MATERIAL AND METHODS: Five chemical disinfectants (Clorox, Banicide, Cidex-7, Biocide, and Multicide) in combination with 3 restorative materials (Dicor, Vita VMK ceramometal porcelain, Midas ADA type III noble casting alloy) were evaluated at 4 different times of immersion (10 minutes, 30 minutes, 24 hours, and 7 days). Changes from baseline for surface roughness and color were evaluated. Surface roughness data were recorded with a surface analyzer and color data in CIE L*a*b* color space were measured with a colorimeter. Data were analyzed with repeated measures analysis of variance and single factor analysis of variance. RESULTS: There were no statistical differences in surface roughness among disinfectants and restorative materials. However, there were statistical differences of changes in color, increase in deltaE and decrease in deltaL, among disinfectants and the noble casting alloy. CONCLUSION: Only 2 of the 3 materials evaluated, Dicor and Vita VMK ceramometal porcelain, can be used with all 5 disinfectants up to 7 days of immersion. Three chemical disinfectants (Biocide, Clorox, and Multicide) caused clinically significant color changes with the noble casting alloy after 7 days of immersion.

Analysis of Variance↗

PubMed1999

Protein kinase C in rat brain is altered by developmental lead exposure.

The absence of learning-related redistribution of hippocampal protein kinase C (PKC) has been correlated with impairment of learning performance induced by developmental lead (Pb) exposure. This study was designed to examine whether the properties of brain PKC are altered by chronic Pb exposure during development. Two-tenth percent Pb acetate was administered to pregnant and lactating dams and then administered to weanlings in drinking water until postnatal day (PN) 56. Effects of Pb on translocation of PKC were studied in brain slices prepared from hippocampus. When the slices were treated with 0.33 microM phorbol-12, 13-dibutyrate (PDBu) for 15 min, a significant increase in PKC activity was observed in the membrane fraction of hippocampal slices from Pb-exposed rats, suggesting that chronic Pb exposure potentiates PDBu-activated PKC translocation. Data obtained from saturation binding assays in the frontal cortices of Pb-exposed rats showed a decrease in the dissociation constant (KD) in both membrane and cytosolic PKC. A decrease in the total binding sites (Bmax) of [3H]PDBu binding was only observed in membrane PKC. Furthermore, developmental Pb exposure decreased PKC-gamma, but not PKC-alpha, -betaII, and -epsilon in the membrane fraction of the hippocampus and the frontal cortex. These results indicate that chronic Pb exposure during development increases phorbol ester binding affinity, enhances phorbol ester-induced translocation of PKC, and down-regulates membrane PKC, mainly PKC-gamma.

Animals↗

PubMed1999

Development of an in vitro human placenta model by the cultivation of human trophoblasts in a fiber-based bioreactor system.

The in vitro human trophoblast culture system is of significant importance in the study of human placenta development and its role as the transport organ between maternal and fetal circulations in normal physiology and pathology pregnancy. But conventional in vitro model systems fail to reproduce many important features of human placenta in vivo. In our study, a perfusion bioreactor system was developed with a chemically modified poly(ethylene terephthalate) (PET) fibrous matrix as the cell culture scaffold. The dual compartment design of the bioreactor simulates maternal and fetal circulation systems in vivo. First trimester human trophoblast cells readily attached on a chemically modified PET fiber surface. The detection of human fibronectin showed that cells were able to form three-dimensional structures by aggregation and bridging between fibers. Moreover, metabolic and hormone secretion data showed that cells in this perfusion culture system maintained their normal functional activities. The results of this study demonstrate the feasibility of tissue engineering human trophoblast cells in a perfusion bioreactor system for the development of an in vitro drug testing model system.

Biocompatible Materials↗

PubMed1999

Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice.

Aquaporin-1 (AQP1) water channels are expressed widely in epithelia and capillary endothelia involved in fluid transport. To test whether AQP1 facilitates water movement from capillaries into the peritoneal cavity, osmotically induced water transport rates were compared in AQP1 knockout [(-/-)], heterozygous [(+/-)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8. Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma. For measurement of water transport, 2 ml of saline containing 300 mM sucrose (600 mosM) were infused rapidly into the peritoneal cavity via a catheter. Serial fluid samples (50 microliter) were withdrawn over 60 min, with albumin as a volume marker. The albumin dilution data showed significantly decreased initial volume influx in AQP1 (-/-) mice: 101 +/- 8, 107 +/- 5, and 42 +/- 4 (SE) microliter/min in (+/+), (+/-), and (-/-) mice, respectively [n = 6-10, P < 0.001, (-/-) vs. others]. Volume influx for AQP4 knockout mice was 100 +/- 8 microliters/min. In the absence of an osmotic gradient, 3H2O uptake [half time = 2.3 and 2.2 min in (+/+) and (-/-) mice, respectively], [14C]urea uptake [half time = 7.9 and 7.7 min in (+/+) and (-/-) mice, respectively], and spontaneous isosmolar fluid absorption from the peritoneal cavity [0.47 +/- 0.05 and 0.46 +/- 0.04 ml/h in (+/+) and (-/-) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis.

Animals↗

PubMed1999

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice.

The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia and aquaporin-4 (AQP4) in airway epithelia. To test whether these water channels facilitate fluid movement between airspace, interstitial, and capillary compartments, we measured passive and active fluid transport in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeability (Pf) was measured in isolated perfused lungs by a pleural surface fluorescence method. Pf was remarkably reduced in AQP1 (-/-) mice (measured in cm/s x 0.001, SE, n = 5-10: 17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP1 [+/-]; 1.7 +/- 0.3 AQP1 [-/-]; 12 +/- 1 AQP4 [-/-]). Microvascular endothelial water permeability, measured by a related pleural surface fluorescence method in which the airspace was filled with inert perfluorocarbon, was reduced more than 10-fold in AQP1 (-/-) vs. (+/+) mice. Hydrostatically induced lung interstitial and alveolar edema was measured by a gravimetric method and by direct measurement of extravascular lung water. Both approaches indicated a more than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to 10-cm H2O increase in pulmonary artery pressure for five minutes. Active, near-isosmolar alveolar fluid absorption (Jv) was measured in in situ perfused lungs using 125I-albumin as an airspace fluid volume marker. Jv (measured in percent fluid uptake at 30 min, n = 5) in (+/+) mice was 6.0 +/- 0.6 (37 degrees C), increased to 16 +/- 1 by beta-agonists, and inhibited to less than 2.0 by amiloride, ouabain, or cooling to 23 degrees C. Jv (with isoproterenol) was not affected by aquaporin deletion (18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP1 [-/-]; 16.3 +/- 1.7 AQP4 [-/-]). These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport. AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid.

Animals↗

PubMed1999

Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice.

It has been controversial whether high water permeability in the thin descending limb of Henle (TDLH) is required for formation of a concentrated urine by the kidney. Freeze-fracture electron microscopy (FFEM) of rat TDLH has shown an exceptionally high density of intramembrane particles (IMPs), which were proposed to consist of tetramers of aquaporin-1 (AQP1) water channels. In this study, transepithelial osmotic water permeability (Pf) was measured in isolated perfused segments (0.5-1 mm) of TDLH in wild-type (+/+), AQP1 heterozygous (+/-), and AQP1 null (-/-) mice. Pf was measured at 37 degrees C using a 100 mM bath-to-lumen osmotic gradient of raffinose, and fluorescein isothiocyanate (FITC)-dextran as the luminal volume marker. Pf was (in cm/s): 0.26 +/- 0.02 ([+/+]; SE, n = 9 tubules), 0.21 +/- 0.01 ([+/-]; n = 12), and 0.031 +/- 0.007 ([-/-]; n = 6) (P < 0.02, [+/+] vs. [+/-]; P < 0.0001, [+/+] vs. [-/-]). FFEM of kidney medulla showed remarkably fewer IMPs in TDLH from (-/-) vs. (+/+) and (+/-) mice. IMP densities were (in microm-2, SD, 5-12 micrographs): 5,880 +/- 238 (+/+); 5,780 +/- 450 (+/-); and 877 +/- 420 (-/-). IMP size distribution analysis revealed mean IMP diameters of 8.4 nm ([+/+] and [+/-]) and 5.2 nm ([-/-]). These results demonstrate that AQP1 is the principal water channel in TDLH and support the view that osmotic equilibration along TDLH by water transport plays a key role in the renal countercurrent concentrating mechanism. The similar Pf and AQP1 expression in TDLH of (+/+) and (+/-) mice was an unexpected finding that probably accounts for the unimpaired urinary concentrating ability in (+/-) mice.

Animals↗

PubMed1999

[Multiple inhibitory mechanisms of wild-type p16 gene transfer into human bladder cells by retroviral vector].

OBJECTIVE: To investigate the inhibitory mechanisms of wild-type p16 gene transfer into human bladder cancer cells with or without endogenous p16 gene expression. METHODS: p16 recombinant retrovirus vector was constructed and transfected in human bladder cancer cell EJ and 253J. Northern blot analysis and immunocytochemistry were used to detect the expression of exogenous p16 gene. Flow cytometry analysis was used to detect tumor cell cycle. Electronic microscope and in situ labelling apoptotic DNA fragment detection (TUNEL) was used to detect tumor cell apoptosis after gene transfection. Tumorigenicity was observed in nude mice. RESULTS: The growth rate of the transfected EJ cells was significantly retarded, the majority of transfected EJ cells were arrested on G(0) + G(1) phases of cell cycle, tumorigenicity of the transfected cells was reduced on nude mice. H-ras gene expression in transfected EJ cells reduced as compared with non-transfection. Apoptotic cells were observed in transgenic 253J cells. CONCLUSIONS: Malignant proliferation of bladder cancer cells can be inhibited by exogenous p16 gene transfection via different molecular pathway.

Animals↗

PubMed1999

[The mechanism of p16 gene inactivation in human bladder transitional cell carcinoma].

OBJECTIVE: To figure out the mechanism of p16 gene inactivation in human bladder transitional cell carcinoma (BTCC). METHODS: p16 gene was analyzed for genetic alterations by Southern blot analysis, PCR-SSCP and DNA methylation analysis in 52 cases of transitional cell carcinoma of bladder. RESULTS: p16 gene deletion was found in 11 of 52 (21.15%) BTCCs, only one tumor showed point mutation on p16 exon 2, nineteen cases of BTCCs (36.53%) showed p16 gene 5' CpG island methylation. CONCLUSION: There was a statistically significant association between p16 gene deletion and early stage, well differentiated tumors. Additionally, a statistically significant correlation was also noticed between p16 gene 5' CpG island methylation and tumors in late stage with poor cell differentiation.

Blotting, Southern↗

PubMed1999

[Separation of alkylphenols in oil field water by micellar electrokinetic chromatography].

The abundance of alkylphenols in the system of water, oil and rock is of great geochemistry significance. The analysis of alkylphenols in oil field water using micellar electrokinetic chromatography with UV detection is described. The different variables that affect separation were studied and optimized. The results show that better separation was obtained with the borate concentration of 47.5 mmol/L, the SDS concentration of 70.0 mmol/L, pH 9.15, separation current of 100 microA, capillary temperature 20 degrees C. The organic additive(beta-CD) could partly improve separation. Water sample was introduced into the capillary by pressure of 5 kPa for several seconds. Detection wavelength was 200 nm and reference wavelength at 350 nm for all experiments. For the oil field water sample, the reproducibility of directly injected oil field water after filtration through a membrane filter of 0.45 micron pore size was far from good and it's concentrations of alkylphenols were too low to be detected. Therefore, a method of separation and enrichment by a column packed with tributyl phosphate(TBP) extraction resin was applied for analysis of TZ4 oil field water. Qualitative analysis show that there are phenol, o-cresol, m-cresol and p-cresol in this water sample and phenol is the main component and it's quantity is more than other alkylphenols. It's recoveries from the oil field water were 91.5%-95.3%. The results were satisfactory.

Chromatography, Micellar Electrokinetic Capillary↗

PubMed1999

[The development of an intelligent vision testing instrument].

The paper introduces an intelligent vision testing instrument, which works on automatic method or manual method. The examinee inputs his or her judgement about the direction of the letter "E" with remote control. The system examines and judges the examinee's judgement, and then prints the testing report. The vision testing range is from logarithm vision 3.0 to 5.3. The distance between examinee and optometer can be measured automatically by the system with infrared and ultrasonic testing functions and a good accuracy.

Diagnosis, Computer-Assisted↗

PubMed1998

Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice.

To investigate the role of aquaporin-1 (AQP1) water channels in proximal tubule function, in vitro proximal tubule microperfusion and in vivo micropuncture measurements were done on AQP1 knockout mice. The knockout mice were generated by targeted gene disruption and found previously to be unable to concentrate their urine in response to water deprivation. Unanesthetized knockout mice consumed 2.8-fold more fluid than wild-type mice and had lower urine osmolality (505 +/- 40 vs. 1081 +/- 68 milliosmolar). Transepithelial osmotic water permeability (Pf) in isolated microperfused S2 segments of proximal tubule from AQP1 knockout [-/-] mice was 0.033 +/- 0.005 cm/s (SE, n = 6 mice, 37 degreesC), much lower than that of 0.15 +/- 0.03 cm/s (n = 8) in tubules from wild-type [+/+] mice (P < 0.01). In the presence of isosmolar luminal perfusate and bath solutions, spontaneous fluid absorption rates (nl/min/mm tubule length) were 0.31 +/- 0.12 (-/-, n = 5) and 0.64 +/- 0.15 (+/+, n = 8). As determined by free-flow micropuncture, the ratios of tubular fluid-to-plasma concentrations of an impermeant marker TF/P in end proximal tubule fluid were 1.36 +/- 0. 05 (-/-, n = 8 mice [53 tubules]) and 1.95 +/- 0.09 (+/+, n = 7 mice [40 tubules]) (P < 0.001), corresponding to 26 +/- 3% [-/-] and 48 +/- 2% [+/+] absorption of the filtered fluid load. In collections of distal tubule fluid, TF/P were 2.8 +/- 0.3 [-/-] and 4.4 +/- 0.5 [+/+], corresponding to 62 +/- 4% [-/-] and 76 +/- 3% [+/+] absorption (P < 0.02). These data indicate that AQP1 deletion in mice results in decreased transepithelial proximal tubule water permeability and defective fluid absorption. Thus, the high water permeability in proximal tubule of wild-type mice is primarily transcellular, mediated by AQP1 water channels, and required for efficient near-isosmolar fluid absorption.

Animals↗

PubMed1998

Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels.

Water channel aquaporin-1 (AQP1) is strongly expressed in kidney in proximal tubule and descending limb of Henle epithelia and in vasa recta endothelia. The grossly normal phenotype in human subjects deficient in AQP1 (Colton null blood group) and in AQP4 knockout mice has suggested that aquaporins (other than the vasopressin-regulated water channel AQP2) may not be important in mammalian physiology. We have generated transgenic mice lacking detectable AQP1 by targeted gene disruption. In kidney proximal tubule membrane vesicles from knockout mice, osmotic water permeability was reduced 8-fold compared with vesicles from wild-type mice. Although the knockout mice were grossly normal in terms of survival, physical appearance, and organ morphology, they became severely dehydrated and lethargic after water deprivation for 36 h. Body weight decreased by 35 +/- 2%, serum osmolality increased to >500 mOsm, and urinary osmolality (657 +/- 59 mOsm) did not change from that before water deprivation. In contrast, wild-type and heterozygous mice remained active after water deprivation, body weight decreased by 20-22%, serum osmolality remained normal (310-330 mOsm), and urine osmolality rose to >2500 mOsm. Urine [Na+] in water-deprived knockout mice was <10 mM, and urine osmolality was not increased by the V2 agonist DDAVP. The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication. AQP1 is thus required for the formation of a concentrated urine by the kidney.

Animals↗

PubMed1998

The relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension.

To study the relationship between constitutive nitric oxide synthase (cNOS) and pregnancy induced hypertension (PIH), cNOS expression and localization in placental villi of PIH patients (n = 15) and normal pregnancy patients (n = 15) were immunohistochemically studied. The positive immunostaining of cNOS was located in trophocytes and cytoplasm of vascular endothelial cells. The positive rate in PIH patients was much higher than that in cases of normal pregnancy. The positive rates were 34.40% in mild, 44.74% in middle and 50.14% in severe PIH patients respectively. There was a significant difference in positive rate among the mild, middle and severe PIH patients (P < 0.01). It is concluded that the increase of cNOS activity probably was the results of protective or compensatory mechanism of PIH course.

Adult↗

PubMed1998

Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence.

The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. naloxone. In butorphanol-dependent rats, the spinal kappa-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal delta- and mu-opioid receptors did. In contrast, the spinal mu-opioid receptor became more sensitive than the delta-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.

Animals↗

PubMed1998

Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice.

Aquaporin (AQP)-3 and AQP4 water channels are expressed at the basolateral membrane of mammalian collecting duct epithelium. To determine the contribution of AQP4 to water permeability in the initial inner medullary collecting duct (IMCD), osmotic water permeability (Pf) was compared in isolated perfused IMCD segments from wild-type and AQP4 knockout mice. The AQP4 knockout mice were previously found to have normal gross appearance, survival, growth, and kidney morphology and a mild urinary concentrating defect (T. Ma, B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman, J. Clin. Invest. 100: 957-962, 1997). Transepithelial Pf was measured in microdissected IMCDs after 18-48 h of water deprivation and in the presence of 0.1 nM arginine vasopressin (to make basolateral Pf rate limiting). Pf values (37 degrees C; means +/- SE in cm/s x 10(-3)) were 56.0 +/- 8.5 for wild-type mice (n = 5) and 13.1 +/- 3.7 for knockout mice (n = 6) (P < 0.001). Northern blot analysis of kidney showed that transcript expression of AQP1, AQP2, AQP3, and AQP6 were not affected by AQP4 deletion. Immunoblot analysis indicated no differences in protein expression of AQP1, AQP2, or AQP3, and immunoperoxidase showed no differences in staining patterns. Coexpression of AQP3 and AQP4 in Xenopus laevis oocytes showed additive water permeabilities, suggesting that AQP4 deletion does not affect AQP3 function. These results indicate that AQP4 is responsible for the majority of basolateral membrane water movement in IMCD but that its deletion is associated with a very mild defect in urinary concentrating ability.

Animals↗

PubMed1998

Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels.

T1alpha is a protein of unknown function that is expressed at the plasma membrane in epithelia involved in fluid transport, including type I alveolar epithelial cells, choroid plexus, and ciliary epithelium. The purpose of this study was to test the hypothesis that T1alpha functions as a water channel or a regulator of aquaporin-type water channels that are coexpressed with T1alpha. Two complementary DNAs (cDNAs) (hT1alpha-1 and hT1alpha-2) encoding human isoforms of T1alpha were cloned by homology to the rat T1alpha coding sequence. The cDNAs encoded 164 (hT1alpha-1) and 162 (hT1alpha-2) amino acid proteins with high homology to rat T1alpha in a putative membrane-spanning domain. hT1alpha-1 transcripts of 2. 6 and 1.4 kb were detected in human lung, heart, and skeletal muscle, and a single hT1alpha-2 transcript of 1.2 kb was detected in human lung. Rat and mouse T1alpha were isolated by reverse transcription-polymerase chain reaction and confirmed by DNA sequence analysis. Expression of mouse, rat, and human T1alpha isoforms in Xenopus oocytes did not increase osmotic water permeability (Pf) above that in water-injected oocytes, nor was there an effect of protein kinase A or C activation; Pf was increased > 10-fold in positive control oocytes expressing aquaporin (AQP)1 or AQP5. Coexpression of AQP1 or AQP5 with excess T1alpha gave Pf not different from that in oocytes expressing AQP1 or AQP5 alone. Oocyte plasma membrane localization of epitope-tagged T1alpha protein was confirmed and quantified by immunoprecipitation of microdissected plasma membranes. Quantitative densitometry indicated that the single-channel water permeability of T1alpha is under 2 x 10(-16) cm3/s, suggesting that T1alpha is not involved in the high transalveolar water permeability in intact lung. The cloning of hT1alpha isoforms may permit the development of an assay of type I cell antigen in airspace fluid as a marker of human lung injury.

Amino Acid Sequence↗

PubMed1998

Excitatory amino acids and lead-induced neurotoxicity.

The NMDA receptor non-competitive antagonist, [3H]MK-801, was used as a ligand for an autoradiographic study to determine the effects of lead on NMDA receptor in rat brain. Adult male rats were given lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i.p. for 7 days. Lead levels were detected in blood (41.1 micrograms/dl) and brain (16.7-29.4 micrograms/g). Concentrations of lead in various brain regions did not differ. [3H]MK-801 binding was heterogeneous throughout the brain with the following order of binding densities: hippocampal formation > cortex > caudate-putamen > thalamus > brainstem. Lead exposure caused a decrease in [3H]MK-801 binding to NMDA receptors in the hippocampal formation including CA2 stratum radiatum, CA3 stratum radiatum and presubiculum, and in the agranular insular, cingulate, entorhinal, orbital, parietal and perirhinal areas of cerebral cortex. In another experiment, female rats were exposed pre- and post-natally from the 4th +/- 1 post conception day with 1,000 ppm lead in their drinking water. This treatment continued after weaning. No effects of lead on [3H]MK-801 binding were found at postnatal day (PM) 28. However, lead caused a significant increase in [3H]MK-801 binding in the hippocampus including CA1 and CA2, and in the occipital and temporal cortical areas at PN 56 and at PN 112. Increases in [3H]MK-801 binding were also found in entorhinal cortex and dentate gyrus at PN 112. The hippocampal formation is a critical neural structure for learning and memory processes, whereas cortical and subcortical regions are involved in the modulation of complex behavioral processes. NMDA receptors have been shown to play a key role in synaptic plasticity underlying learning and memory. Therefore, lead-induced alterations of ligand binding to NMDA receptors in the hippocampal formation and cortical areas may play a role in lead-induced neurotoxicity.

Animals↗