Distribution of tin in brain subcellular fractions following the administration of trimethyl tin and triethyl tin to the rat

The time course of tin distribution in homogenates and subcellular fractions of rat brain was determined following the acute administration of trimethyl tin (TMT) and triethyl tin (TET) to the rat. Exposure to TMT resulted in lower concentrations but greater persistence of tin in subcellular fractions compared to exposure to TET. A delayed accumulation of tin in the mitochondrial fraction was observed following the administration of TMT but not TET. Analysis of total protein and mitochondrial markers did not reveal differences between the compositions of mitochondrial fractions prepared from control and TMT-treated subjects.     

Fatty acid changes in rat brain ethanolamine phosphoglycerides during and following chronic exposure to trichloroethylene

Rats were exposed by continuous inhalation to a moderate level of trichloroethylene (1720 mg/m3). The fatty acid pattern of brain ethanolamine phosphoglycerides was examined during exposure and after an additional exposure-free period. Alterations in the fatty acid pattern were noted after 30 days of exposure. An increased ratio of linoleic acid-derived (n-6) to linolenic acid-derived (n-3) fatty acids was observed in the cerebral cortex, the hippocampus, and the brain stem. Of the major fatty acids, arachidonic acid (20:4(n-6)) was increased in the cerebral cortex and the brain stem, while docosahexenoic acid (22:6(n-3)) was decreased in the cerebral cortex and the hippocampus. A further change in these fatty acids was observed in the cerebral cortex following a longer exposure period of 90 days. The 22-carbon linoleic acid-derived fatty acids were also increased after 90 days of exposure. These findings imply that trichloroethylene affects the metabolism of ethanolamine phosphoglyceride fatty acids in the rat brain by inhibiting desaturation of the linolenic acid family and by increasing desaturation of the linoleic acid family. The effect of trichloroethylene was partially reversible, since a postexposure solvent-free period revealed a rapid partial normalization of 22:6(n-3), which is the most important fatty acid of the linolenic acid family in the rat brain. However, the precursor of this fatty acid, 22:5(n-3), was decreased during the first 10 exposure-free days. This suggests that desaturation over the first steps was still impaired. A complete normalization of the fatty acid pattern was not observed during the 30-day solvent-free period. The decreased number of double bonds and shorter chain lengths detected after solvent exposure is consistent with the idea of a compensatory remodeling of membrane lipid composition based on membrane stability with regard to phase preference.     

Tin distribution in adult and neonatal rat brain following exposure to triethyltin

The uptake, distribution, and elimination of tin were determined in adult and neonatal (Postnatal Day 5) rat brain following ip administration of triethyltin bromide (TET). Groups of five adult CD rats were killed at 10 min, 1 hr, 4 hr, 24 hr, 5 days, or 10 days following acute exposure to 6.0 mg/kg TET; an additional group of adult animals was killed at 24 hr following exposure to either 3.0, 6.0, or 9.0 mg/kg (N = 5/dosage). The time course for tin distribution in 5-day-old rat pups was determined by killing pups 10 min, 30 min, 1 hr, 4 hr, 8 hr, 12 hr, 24 hr, 5 days, 10 days, or 22 days following exposure to either 3.0 or 6.0 mg/kg TET (N = 4/dosage/time). Tin analyses were performed by flameless atomic absorption spectrophotometry. The $\text{t}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ for total tin in the adult rat brain following 6.0 mg/kg TET was determined to be 8.0 days. The maximum concentration in the adult was reached at 24 hr and corresponded to 4.6, 9.6, and 16.6 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across all brain areas studied. For animals exposed to 6.0 mg/kg TET on Postnatal Day 5, the $\text{t}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ for total tin in the brain was 7.3 days. A maximum concentration of 9.9 ng tin/mg protein was reached at 8 hr postexposure. The rate of elimination of tin from the brain (as measured by the elimination rate constant k_el) did not differ significantly between adults and neonates. However, due to a dilution effect by the rapid brain growth of the neonate, the concentration of tin in the neonatal brain following TET administration decreased significantly faster than that in the adult.     

Perinatal exposure to cannabinoids alters neurochemical development in rat brain

Adult female rats received daily oral doses of delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-THC and cannabidiol (CBD) throughout gestation and lactation. The offspring were sacrificed at various ages and tissue samples of cerebral cortex and striatum were assayed for alpha 1-adrenergic and D2-dopaminergic receptors, respectively. In addition, tyrosine hydroxylase activity was determined in the striatum. The Kd for ligand binding to alpha 1 receptors in the cerebral cortex was significantly increased in 10-day-old offspring exposed to CBD. Significant increases in the Bmax of these receptors occurred at 20 days of age following perinatal exposure to delta 9-THC or delta 8-THC. Exposure to CBD increased the Kd of D2 receptors in the striatum of 10 and 20-day-old offspring compared to control. There were no significant treatment effects on the Bmax of D2 receptors in the striatum at any age. Tyrosine hydroxylase activity was significantly decreased only at 60 days of age in offspring exposed to delta 8-THC or CBD. These results differ from those previously reported with a crude marihuana extract, suggesting that changes in the development of brain catecholamine mechanisms resulting from perinatal exposure to marihuana extracts may be due to an additional constituent of the extract, interactions between specific cannabinoids or other unknown factors.     

Fetal brain damage in the rat following prenatal exposure to cocaine

The aim of this study was to identify fetal brain damage induced by 1) prenatal cocaine exposure or 2) physical procedures causing temporary constriction or occlusion of the uterine vessels in pregnant rats. Brains were examined from rat fetuses killed 48 hours after the dam was given one or more intraperitoneal doses of cocaine (50–70 mg/kg) on day 16 of gestation. Only brains from fetuses with hemorrhage in the extremities were examined, as this indicated they had undergone a circulatory disturbance. Four of the 10 brains examined showed bilateral necrosis and cavitation in the cerebral cortex. There were also hemorrhage and ectopic outgrowths in the corpus striatum, bilateral cavitation in the brainstem and vacuolization in the lens of the eye. A similar type and distribution of damage was seen in rat fetal brains from dams treated by temporary occlusion of the uterine vessels or direct handling of the pregnant uterus on day 16 of gestation and examined 48 hours later. It is proposed that the procedures act through the common mechanism of constriction/occlusion of the uterine vessels. The damage to the fetuses appears to be due to hemorrhage from the fetal vessels and ischemia. These findings are discussed in relation to cocaine use during human pregnancy.     

Acute and long-term neuronal deficits in the rat olfactory bulb following alcohol exposure during the brain growth spurt

This study demonstrates that there is a relative recovery in the number of olfactory bulb granule cells following an initial alcohol-induced deficit, while the number of mitral cells remains permanently and severely depressed. The importance of pattern of exposure in influencing the severity of alcohol-induced neuronal loss in the olfactory bulb is also demonstrated. Sprague-Dawley rat pups were reared artificially and were administered alcohol over postnatal days (PD) 4 through 9, a period of rapid brain growth comparable to part of the human third trimester. Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 5.1% or 10.2% solution. A third group received a higher daily alcohol dose of 6.6 g/kg administered continuously as a 2.5% solution. Pups were either sacrificed on PD 10 or were allowed to grow to adulthood and sacrificed on PD 90. The number of mitral cells and granule cells and the area of the subependymal zone were determined from single sections. On PD 10, immediately following the alcohol exposure, both the mitral cells and the granule cells were significantly reduced in number, relative to controls, in both of the groups receiving the concentrated (5.1% and 10.2%) alcohol treatments. On PD 90, however, only the mitral cell number remained significantly reduced in the groups receiving the concentrated solutions, while the number of granule cells no longer differed significantly from that of controls. The group receiving the higher daily dose (6.6 g/kg) in continuous fractions had no significant cell loss at 10 or 90 days of age. There was no significant effect of any treatment or at any age on the area of the subependymal zone. These results suggest that the acute and long-term effects of alcohol on neuronal number vary among neuronal populations and that compensatory changes may occur in some neuronal complements following cessation of the alcohol exposure.     

Toluene levels in blood and brain of rats during and after respiratory exposure

Eighty rats were exposed to 575 ppm toluene by inhalation for up to 240 min. Animals in one group were sacrificed during exposure at 15, 30, 60, 120, or 240 min. Following a 240-min exposure, groups of rats were sacrificed at 15, 30, 120, or 240 min. Blood was drawn from the vena cava of sacrificed subjects. Brains were extracted and homogenized. Blood and brain tissue were assayed for toluene by gas chromatography. One-compartment pharmacokinetic models were fitted to predict toluene levels in blood and whole brain as a function of time. Estimated asymptotes were 10.5 ppm (μg/g) for venous blood and 18.0 ppm (μg/g) for brain. Blood and brain toluene levels achieved 95% of estimated asymptotes in 53 and 58 min, respectively. Brain and blood toluene levels did not rise at significantly different rates. Though the difference was small, brain toluene level fell significantly more rapidly than toluene level in blood. In cases where other data were available in the literature on rodents or man, the results reported here agreed well with earlier data.     

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

Wistar rat pups were administered either a high dose of lead acetate (400 g lead/g body weight/day) or a low dose (100 g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.     

Altered gene expression during rat Wolffian duct development following di(n-butyl) phthalate exposure.

Di(n-butyl) phthalate (DBP) is a common plasticizer and solvent that disrupts androgen-dependent male reproductive development in rats. In utero exposure to 500 mg/kg/day DBP on gestation days (GD) 12 to 21 decreases androgen biosynthetic enzymes, resulting in decreased fetal testicular testosterone levels. One consequence of prenatal DBP exposure is malformed epididymides in adult rats. Reduced fetal testosterone levels may be responsible for the malformation, since testosterone is required for Wolffian duct stabilization and their development into epididymides. Currently, little is understood about the molecular mechanisms of Wolffian duct differentiation. The objective of this study was to identify changes in gene expression associated with altered morphology of the proximal Wolffian duct following in utero exposure to DBP. Pregnant Crl:CD(R) (SD) rats were gavaged with corn oil vehicle or 500 mg/kg/day DBP from GD 12 to GD 19 or 21. There were only small morphological differences between control and DBP-exposed Wolffian ducts on GD 19. On GD 21, 89% of male fetuses in the DBP dose group showed marked underdevelopment of Wolffian ducts, characterized by decreased coiling. RNA was isolated from Wolffian ducts on GD 19 and 21. Together with empirical information, cDNA microarrays were used to help identify candidate genes that could be associated with the morphological changes observed on GD 21. These candidate genes were analyzed by real-time RT-PCR. Changes in mRNA expression were observed in genes within the insulin-like growth factor (IGF) pathway, the matrix metalloproteinase (MMP) family, the extracellular matrix, and in other developmentally conserved signaling pathways. On GD 19, immunolocalization of IGF-1 receptor protein demonstrated an increase in cytoplasmic expression in the mesenchymal and epithelial cells. There was also a variable decrease in androgen receptor protein in ductal epithelial cells on GD 19. This study provides insight into the effects of antiandrogens on the molecular mechanisms involved in Wolffian duct development. The altered morphology and changes in gene expression following DBP exposure are suggestive of altered paracrine interactions between ductal epithelial cells and the surrounding mesenchyme during Wolffian duct differentiation due to lowered testosterone production.     

Lead retention in blood and brain after preweaning low-level lead exposure in the rat

Newborn rats of the albino Wistar strain were exposed to lead from birth to 20 days of age through mothers milk, from dams which were fed diets containing 0, 0.25, 0.5 or 1.0% powdered lead. Subsequent determination of tissue lead revealed a direct relationship between the lead levels in both blood and brain of the pups and the lead dosage to which they were indirectly exposed via the dams' milk. Lead retention in both tissues was still evident at 100 days of age, with the relative elevation of lead levels being an order of magnitude higher in brain than in blood. There were no obvious signs of lead intoxication in the pups, apart from mild growth retardation in the group with the highest lead burden. However there was a significant retardation in behavioral development observed on two of four measures which were employed. It was concluded that brief exposure to low lead levels in infancy can have long lasting consequences in the brain and in behavior.     

Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period

The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0mg/kg body weight (bw) to groups II, III and IV (n=6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 microm), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be the underlying basis for some of the functional deficits encountered in the later period of life.     

Concentration and origin of choline in the rat brain

Summary In the rat brain the concentration of choline increases with a velocity of 20.5 nMol/g×min immediately after decapitation. This is not due to postmortal disintegration of the tissue but to persisting biochemical reactions in the absence of blood flow. This rise of choline must be considered if the concentration of choline in the living animal is to be established. Taking this fact into account one arrives at a value of 27.5±1.7 nMol Choline/g wet weight.From the arterio-venous difference of choline concentrations it has been postulated that there is an efflux of 7.2±1.5 nMol/g×min from the brain into the blood.After i.v. injection of labelled choline the peak of the specific radioactivity of choline in the brain is reached in less than 1 min but amounts to only one tenth of the specific activity of choline in blood-plasma. The specific activities in both compartments decline in parallel. Thus it can be concluded a) that choline penetrates easily through the blood-brain barrier, but the concentration gradient is directed from brain to blood; and b) that choline is continuously formed in the brain, which process permanently dilutes the quantity of labelled choline and prevents the specific activities in blood and brain from becoming equal. The calculations of turnover-rates in the different reactions leading to the choline containing glycerophosphatides are based on the data obtained. On the basis of these findings it is proposed that in the brain phosphorylated derivatives of ethanolamine (phosphorylethanolamine, cytidinediphosphate-ethanolamine) can be methylated to form the respective choline derivatives.     

Intraneuronal accumulation and persistence of radiolabel in rat brain following in vivo administration of [3H]-chlorisondamine.

1. Chlorisondamine (CHL), a bisquaternary amine, produces a remarkably long-lasting blockade of central responses to nicotine. The mechanism underlying this blockade is not known. The main aim of this study was to test for possible accumulation of [3H]-CHL in rat brain during the period of chronic blockade. 2. Rats received CHL, either systemically (10 mg kg-1) or centrally (10 micrograms i.c.v.). Seven days later, striatal synaptosomes prepared from these animals were tested for nicotine-induced [3H]-dopamine release. This experiment showed that i.c.v. administration of CHL was as effective as systemic administration in producing ex vivo blockade of central nicotinic receptors. 3. Rats received bilateral i.c.v. infusions of [3H]-CHL (10 micrograms) and radioactivity was subsequently quantified in dissected cerebral cortex, striatum, hippocampus, midbrain and cerebellum. Radiolabel was detected at all three survival times (1, 7, and 21 days). Regional heterogeneity was apparent at 7 and 21 days survival. Radiolabel was almost exclusively confined to the insoluble subcellular fraction in all areas sampled. 4. The anatomical distribution of radiolabel was also visualized in brain sections. Rats received bilateral i.c.v. infusions of [3H]-CHL (10 micrograms) and were killed at 1, 7, 21 or 84 days. Immediately before they were killed, all rats were tested behaviourally, and central nicotinic blockade was demonstrated at 1, 7 and 21 days; partial recovery was observed at 84 days. Particularly at longer survival times, tritium was found to be heavily concentrated in the substantia nigra pars compacta, ventral tegmental area, dorsal raphé nucleus, and the granular layer of the cerebellum. 5. The possibility of retrograde axonal transport of radiolabel was then examined. Rats received a unilateral intrastriatal infusion of [3H]-CHL (0.34 or 0.034 micrograms) one week before they were killed. Autoradiographic labelling was largely confined to the site of infusion and to the ipsilateral substantia nigra pars compacta and dorsal raphé nucleus. 6. Thus, after i.c.v. administration, CHL (and/or centrally-formed derivatives) is initially widely distributed within the brain and is then selectively retained within a few brain areas. A persistent accumulation occurs within putative dopaminergic and 5-hydroxytryptaminergic neurones, at least partly through uptake by terminals and/or axons followed by retrograde transport. This persistent and anatomically-selective intraneuronal accumulation possibly underlies the long-term central nicotinic blockade associated with chlorisondamine.     

Functional impairment of blood-brain barrier following pesticide exposure during early development in rats

1. The effect of certain pesticides on the functional integrity of the developing blood-brain barrier (BBB) was studied following single and repeated exposure, and after subsequent withdrawal in rats. 2. Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyrethroid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (BUI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72%, respectively, after 2 h. Residual increases in the BUI were found even after 3 days of the single treatment of QP (28%) and LD (23%). 3. Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recovery from these changes was complete in QP and LD-treated animals after 13 days (PND 18-30) of withdrawal. However, CM showed persistent effects that were normalized only after 43 days (PND 18-60) of withdrawal. 4. A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h. 5. An age-dependent effect of these pesticides was evident from the study showing higher magnitude of BUI changes in 10-day-old rats as compared to that in 15-day-old rats. Furthermore, adult rats did not show any effect on BBB permeability even at a higher dose (1/25th of LD50) of these pesticides given alone or in combination with piperonyl butoxide (600 mg/kg, i.p.) for 3 consecutive days. 6. This study showed that developing BBB is highly vulnerable to single or repeated exposure of certain pesticides. The observed persistent effects during brain development even after withdrawal of the treatment may produce some neurological dysfunction at later life as well.     

Drugs and brain mitochondrial enzymatic activities during post-natal development in rat.

The enzymatic activities of two mitochondrial enzymes, i.e. succinate dehydrogenase and NADH-cytochrome c reductase were investigated in the brain of rats at different stages of post-natal development. In addition, the effect of the pharmacological treatment with two drugs, nicergoline and bamethan, able to interact with the alpha or the beta receptors respectively, was evaluated. The results show that both the enzymatic activities rapidly increase in the first days of extra-uterine life, thus indicating an adaptation of mitochondrial oxidative processes to post-natal environmental conditions. The pharmacological treatment with the two drugs does not induce any changes in the enzymatic activities tested.     

Lack of alterations in thyroid hormones following exposure to polybrominated diphenyl ether 47 during a period of rapid brain development in mice

Thyroid alterations have been shown to occur following exposure to polybrominated diphenyl ether (PBDE) mixtures, possibly indicating that disruptions in thyroid hormone levels may underlie behavior deficits observed in animals following postnatal PBDE exposure. This study determined whether acute postnatal exposure to PBDE-47 would alter thyroid hormones. Mice were dosed with PBDE-47 on postnatal day 10, and serum collected either 1, 5, or 10 days after the dose. No effect was observed on thyroxine and triiodothyronine levels at any age examined. This suggests that the neurological abnormalities reported in mice exposed to PBDE-47 are not due to acute changes in circulating thyroid hormones at these observed periods.     

Kinetics of methyl mercury in blood and brain during chronic exposure in the monkey Macaca fascicularis

The disposition parameters derived from a compartmental model kinetic analysis of blood Hg levels in nonpregnant, adult female Macaca fascicularis given daily doses of MeHg did not vary with either dosage level (50, 70 or 90 micrograms MeHg/kg b.wt.day) or duration of exposure (up to 507 day). In contrast, blood clearance of Hg in pregnant females was dose-dependent; it being higher at the 90 micrograms MeHg/kg b.wt.day than at the lower dosage levels. Hg levels in the brain of adult fascicularis relative to blood Hg also increased at the highest level of exposure. Blood Hg half-life in neonate fascicularis was similar to half-life in their mothers (adults). Finally, the regional distribution of mercury in the brains of adult and neonate fascicularis exposed to low and intermediate levels of MeHg resembles the reported distribution of mercury in the brains of adult and neonate humans environmentally exposed to MeHg. Consequently, M. fascicularis may be an especially appropriate animal model for studying the neurotoxic mechanisms of chronic methyl mercury exposure.     

Changes in rat brain cholinesterase activity and muscarinic receptor density during and after repeated oral exposure to chlorpyrifos in early postnatal development.

The effects of repeated oral exposures to the organophosphorus insecticide chlorpyrifos (CPS) on brain muscarinic receptor densities, together with cholinesterase (ChE) activity, were studied in early postnatal rats. Initially, the effects on esterases from lactational exposure to CPS were investigated in young rats by administering CPS (100, 150, or 200 mg/kg subcutaneously in corn oil) to dams 1 day postpartum, yielding a significant body burden of CPS in the dams for possible excretion in the milk. Brain ChE inhibition in pups was less severe than in dams, whereas liver carboxylesterase (CbxE) inhibition in pups was at the same level as in dams. Because of the limited brain ChE inhibition obtained following lactation, pups were exposed to CPS directly by gavage, using 3 dosing regimens to yield a dose response. The rats were gavaged with CPS in corn oil on alternate days from postnatal day (PND) 1 through PND 21. Rats in the low-dosage group received 11 treatments at 3 mg/kg, those in the medium-dosage group received 3 treatments at 3 mg/kg and 8 at 6 mg/kg, and those in the high dosage group received 3 treatments at 3 mg/kg, 4 at 6 mg/kg, and 4 at 12 mg/kg. ChE activity in brain homogenates were inhibited significantly by 29% and 63% in the low- and high-dosage groups, respectively, on PND 22 and by 17% in the high dosage group on PND 40. Muscarinic receptor densities in brain synaptosomes were reduced using 3H-N-methylscopolamine (NMS) and 3H-quinuclidinyl benzilate (QNB) as ligands, with the effects more prominent from 3H-NMS. Densities of both ligands recovered to the control level several days after terminating treatment. The results indicate that pups are apparently exposed to only limited amounts of chlorpyrifos and/or its oxon through the milk when dams are exposed to extremely high chlorpyrifos levels. In addition, repeated direct oral exposures of early postnatal rats to CPS will result in persistent brain ChE inhibition and will transiently reduce muscarinic receptor density.     

Effect of dibutyltin dilaurate on regional brain polyamines in rats

Administration of dibutyltin dilaurate (DBTL; 0, 20 or 40 mg/kg body wt.) by gavage to rats for 3 consecutive days produced a significant increase in polyamine levels in selected brain areas. At the higher dose of DBTL (40 mg/kg) spermidine levels were raised in pons-medulla, hypothalamus and frontal cortex while spermine levels increased in pons-medulla, hippocampus and frontal cortex regions. At the lower dose (20 mg/kg) only a slight increase in polyamine levels occurred. The observed induction in regional brain polyamines in DBTL-treated rats may lead to disturbances in synaptic function and further enhance its neurotoxic potential.