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PubMed2001

5-HT6 receptor antagonists enhance retention of a water maze task in the rat.

RATIONALE: 5-HT(6) receptors are predominantly located in the brain and may be involved in cognitive processes. The aim of this study was to assess the effects of two potent and selective 5-HT(6) receptor antagonists, SB-271046-A and SB-357134-A, on learning and memory in the rat. METHODS: Spatial learning and memory was assessed by testing the effects of SB-271046-A and SB-357134-A on acquisition and retention of a water maze task. RESULTS: In the water maze, administration of SB-271046-A or SB-357134-A (3 or 10 mg/kg) had no effect on learning per se. At 10 mg/kg, however, both compounds produced a significant improvement in retention of a previously learned platform position when tested 7 days after training. By contrast, the acetylcholinesterase inhibitor, Aricept (donepezil, 0.1, 0.3 mg/kg PO) had no effect in this task. CONCLUSIONS: This study demonstrates that systemic administration of SB-271046-A and SB-357134-A produces improvements in retention of a water maze task in the rat. These data indicate that 5-HT(6) receptor antagonism may be involved in cognitive function.

Animals↗
PubMed2001

Subchronic cocaine produces training paradigm-dependent learning deficits in laboratory rats.

The effect of cocaine on spatial learning was investigated by exposing male Sprague-Dawley rats to 0, 20, or 40 mg/kg cocaine prior to and during training on a water maze task. Half the animals were pretrained on cued trials prior to hidden platform trials, while the remaining animals completed hidden platform trials immediately. Escape latencies for all animals improved with training, but pretrained animals located the hidden platform faster than untrained animals (P<.001). Pretraining also decreased the effect of cocaine. In pretrained animals, only the high dose of cocaine caused significant increases in escape latency (P<.001), while in the untrained group the lower dose of cocaine also caused a significant increase (P<.001). On working memory measures, cocaine affected both the pretrained (P<.01) and untrained (P<.001) groups. Dwell ratio measurements indicated unaffected reference memory in both pretrained (P<.001) and untrained (P<.001) animals, and no significant differences were detected among the treatment conditions in either group (P>.05). Thus, while cocaine did not abolish learning, the efficiency with which the task was learned was compromised. However, this effect was reduced by pretraining.

Animals↗
PubMedDate not supplied

Administration of D,L-fenfluramine to rats produces learning deficits in the Cincinnati water maze but not the Morris water maze: relationship to adrenal cortical output.

Fenfluramine (FEN) is an amphetamine derivative with anorectic properties similar to amphetamine, but without the stimulatory or abuse potential. Administration of FEN produces an immediate release of serotonin as well as inhibits reuptake; ultimately FEN produces a decrease in serotonin stores in the central nervous system. We have previously shown that the administration of FEN to rats results in increased adrenal cortical hormones under resting conditions, without simultaneous elevations in adrenocorticotropin hormone (ACTH). We hypothesized that the adrenal output would be altered following stress and that the altered adrenal output would affect learning and memory, since the adrenal hormones influence learning and memory capability. In this series of experiments, we administered D,L-FEN (15 mg/kg) four times every 2 h on a single day to rats and investigated the effect on hormonal output following forced swim and the effect on sequential learning in the Cincinnati water maze and spatial learning in the Morris maze beginning 3 days after FEN administration. Animals that received FEN had increased corticosterone and aldosterone titers following forced swim relative to control animals, although no differences in ACTH or testosterone were noted. Animals exposed to FEN had lasting deficits in the Cincinnati water maze but not in the Morris water maze, regardless of testing order. These deficits in the Cincinnati water maze appear to be mediated by the elevation in adrenal output since adrenalectomy abolished the effect of FEN. Corticosterone levels were shown to be elevated during the behavioral testing period in animals exposed to FEN.

Adrenal Cortex↗
PubMed2000

Role of EGR1 in hippocampal synaptic enhancement induced by tetanic stimulation and amputation.

Hippocampal neurons fire spikes when an animal is at a particular location or performs certain behaviors in a particular place, providing a cellular basis for hippocampal involvement in spatial learning and memory. In a natural environment, spatial memory is often associated with potentially dangerous sensory experiences such as noxious or painful stimuli. The central sites for such pain-associated memory or plasticity have not been identified. Here we present evidence that excitatory glutamatergic synapses within the CA1 region of the hippocampus may play a role in storing pain-related information. Peripheral noxious stimulation induced excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal cells in anesthetized animals. Tissue/nerve injury caused a rapid increase in the level of the immediate-early gene product Egr1 (also called NGFI-A, Krox24, or zif/268) in hippocampal CA1 neurons. In parallel, synaptic potentiation induced by a single tetanic stimulation (100 Hz for 1 s) was enhanced after the injury. This enhancement of synaptic potentiation was absent in mice lacking Egr1. Our data suggest that Egr1 may act as an important regulator of pain-related synaptic plasticity within the hippocampus.

Amputation, Surgical↗
PubMed1998

Dextromethorphan and dextrorphan in rats: common antitussives--different behavioural profiles.

Dextromethorphan (DM), a widely used and well-tolerated centrally acting antitussive, has been tested in several clinical trials for its antiepileptic and neuroprotective properties. However, the use of DM in these new clinical indications requires higher doses than antitussive doses, which may therefore induce phencyclidine (PCP)-like side-effects (memory and psychotomimetic disturbances) through its metabolic conversion to the active metabolite dextrorphan (DX), a more potent PCP-like non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor than DM. Thus, we compared the behavioural effects in rats of intraperitoneal administration of DM and DX on motor activity in an open field and on learning and memory in the Morris water maze. DM (20, 30, 40 mg/kg) produced a dose-dependent decrease in both locomotion and stereotyped behaviour with a slight ataxia for the highest dose. DX (20, 30, 40 mg/kg) induced a dose-dependent increase in locomotion and stereotypies (swaying, turning) with moderate ataxia. Assessments of learning and memory were performed with lower doses of DM (10, 20, 30 mg/kg) and DX (5, 10, 15 mg/kg) because of motivational deficits (40 mg/kg of DM, 20-40 mg/kg of DX) and motor disorders (30, 40 mg/kg of DX) in the cue learning procedure. DX (10, 15 mg/kg) impaired spatial learning with a long-lasting effect for the highest dose whereas 5 mg/kg of DX and DM (10-30 mg/kg) did not. Only 15 mg/kg of DX appeared to slightly impair working memory. DM (10-30 mg/kg) and DX (5-15 mg/kg) did not impair reference memory. Thus, the two antitussives DM and DX induced different behavioural effects suggesting sedative effects for DM and PCP-like effects for DX. However, PCP-like side-effects with DM remain possible through its metabolic conversion to DX, with very high doses and/or in extensive metabolizers and/or in aged subjects prone to cognitive dysfunction. Therefore, the identification of DM metabolism phenotype, an adapted prescription and a pharmacological modulation of the DM metabolism may avoid adverse effects.

Animals↗
PubMedDate not supplied

The role of metabotropic glutamate receptor 5 in learning and memory processes.

Metabotropic glutamate receptor 5 (mGluR5), a subtype in the group I mGluRs, couples to phospholipase C through Gq protein. Stimulation of mGluR5 leads to the release of calcium from intracellular stores and protein kinase C activation. In addition, links to different ion channels and other signaling mechanisms have also been revealed. MGluR5s are mainly localized postsynaptically on the periphery of synap-ses. MGluR5s have been implicated in synaptic plasticity and learning and memory. The development of the highly potent and selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has facilitated the understanding of the roles of mGluR5s in the central nervous system. Both in vitro and in vivo studies have demonstrated that the activation of mGluR5s is necessary for some forms of long-term potentiation and long-term depression in different brain regions. Investigations of the effects of MPEP in various behavioral paradigms have concluded that mGluR5s play a critical role in aversive learning tasks and in hippocampal-dependent spatial learning. However, MPEP has proved ineffective in certain other learning tasks. MGluR5 knockout mice have shown impairments in water maze and radial arm maze performance as well as in contextual fear conditioning, but not in cue conditioning. This review summarizes recent advances reported on mGluR5 function in synaptic plasticity, learning and memory. The current development of positive and negative allosteric modulators of mGluR5 will provide new pharmacological tools to enhance our knowledge of these receptors in physiological and pathophysiological processes and will further facilitate new investigations on mGluR5 as a therapeutic target for a range of neurological and psychological disorders.

Animals↗
PubMed2005

Treatment with an amyloid-beta antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer's disease.

PDAPP transgenic mice overexpress a mutant form of human amyloid precursor protein under control of the platelet-derived growth factor promoter in CNS neurons that causes early onset, familial Alzheimer's disease in humans. These mice, on a mixed genetic background, have been shown to have substantial learning impairments from early ages, as well as an age-dependent decline in learning ability that has been hypothesized to be caused by amyloid-beta (Abeta) accumulation. The goals of this study were to determine: (1) whether PDAPP mice on a pure C57BL/6 background develop more severe age-dependent learning deficits than wild-type mice; (2) if so, whether Abeta accumulation accounts for the excessive decline in learning ability; and (3) whether the learning deficits are reversible, even after significant Abeta deposition. At 4-6, 10-12, or 17-19 months of age, PDAPP and littermate wild-type mice on a C57BL/6 background were tested on a 5 week water maze protocol in which the location of the escape platform changed weekly, requiring the mice to repeatedly learn new information. PDAPP mice exhibited impaired spatial learning as early as 4 months (pre-Abeta deposition), and the performance of both wild-type and PDAPP mice declined with age. However, PDAPP mice exhibited significantly greater deterioration with age. Direct evidence for the role of Abeta accumulation in the age-related worsening in PDAPP mice was provided by the observation that systemic treatment over several weeks with the anti-Abeta antibody 10D5 reduced plaque deposition, increased plasma Abeta, improved hippocampal long-term potentiation, and improved behavioral performance in aged PDAPP mice with substantial Abeta burden.

Amyloid beta-Protein Precursor↗
PubMed2004

Effect of intermittent hypoxia on long-term potentiation in rat hippocampal slices.

Intermittent hypoxia (IH) during sleep has been shown to induce apoptosis in a time-dependent manner and spatial learning deficits in adult rats. Recently, we have demonstrated that IH induced significant decreases in Ser-133-phosphorylated cAMP-response element-binding protein (pCREB) without changes in total CREB. The expression of cleaved caspase 3 in the hippocampal CA1, a marker of apoptosis, peaked at 3 days of IH and returned to normoxic values at 14 days of IH. In addition, biphasic changes in spatial task learning were correlated with the CREB phosphorylation time course. In the present study, the rat hippocampal slice preparation was used to evaluate the ability to induce and maintain a CA1 population spike long-term potentiation (PS-LTP) in room air (RA)-maintained and IH-exposed rats. A significant decrease in the ability to sustain PS-LTP for 15 min in slices prepared from IH-exposed rats for either 3 days (34% of total) or 7 days (51% of total) as compared to slices prepared from RA-maintained rats (76% of total) was observed. These results suggest that the diminishment in the ability of neuronal tissue to express and sustain PS-LTP is correlated with previously reported biphasic changes in CREB phosphorylation and programmed cell death.

Action Potentials↗
PubMed2004

Survey of embryonic stem cell line source strains in the water maze reveals superior reversal learning of 129S6/SvEvTac mice.

The availability of pluripotent embryonic stem (ES) cells for gene targeting has resulted in laboratory mice becoming important animal models of human neurological disease. Inbred strains of mice differ in many behavioural phenotypes, such that the same gene mutation can appear to have different phenotypic effects when introduced onto different genetic backgrounds. Prior knowledge of the behavioural phenotypes of the inbred strains used for gene targeting would, therefore, allow the selection of the most appropriate genetic background for the hypothesis to be tested. With this in mind, we tested eight strains of mice (129S1/SvImJ, 129S2/SvPasIcoCrlBR, 129S6/SvEvTac, B6129SF1/J, C57BL/6J, C57BL/6N, LP/J and SM/J), including the sources of five ES cell lines commonly used for gene targeting, in the spatial (submerged platform) version of the Morris water maze, the most widely used paradigm to evaluate the cognitive abilities of genetically modified mice. The three 129 substrain sources of ES cell lines demonstrated spatial learning in the water maze that was superior to that of C57BL/6J, the inbred strain most commonly used for the maintenance and phenotypic testing of mutations. In addition, 129S6/SvEvTac was unique amongst the eight strains tested in having a particular capacity for reversal learning, when the submerged platform was relocated to the opposite quadrant. We conclude that some substrains of 129 could provide suitable genetic backgrounds for testing gene mutations that might be expected to impair cognitive function, thus negating the need to backcross to C57BL/6J, thereby avoiding the so-called "flanking gene problem".

Analysis of Variance↗
PubMed1997

Vasopressin fragment, AVP-(4-8), improves long-term and short-term memory in the hole board search task.

The hole board search task (HBST) measures long-term and short-term memory, operationally defined as reference memory and working memory. The HBST is an open-field spatial learning test. Previously, we have shown that desglycinamide(Arg8) vasopressin (DGAVP) modulated reference memory, working memory, spatial sequence memory, and learning in the HBST in a dose-dependent manner (Vawter MP, Van Ree JM. Effects of des-glycinamide-sup-9-(arginine-sup-8) vasopressin upon spatial memory in the hole-board search task. Psychobiology 1995; 23: 45-51). To examine the potential active site of the DGAVP molecule, the fragment of the vasopressin amino acid sequence, [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8)), was administered 1 h prior to training in the HBST. Three groups received either 0, 0.3 microgram, or 1 microgram AVP-(4-8). A repeated measures MANOVA showed the AVP-(4-8) pretreatment factor to be significant (P = 0.048) on the reference memory measure, but not the working memory or learning measures. Interactions between peptide x sessions for reference memory (P = 0.015), working memory (P = 0.003) and learning (P = 0.010) indicated differences in improvement over sessions between placebo- and peptide-treated groups. Post hoc comparisons revealed that the AVP-(4-8) fragment in a dose of 0.3 microgram increased reference memory on the fourth, fifth and sixth acquisition sessions compared with placebo or 1 microgram AVP-(4-8) pretreated groups. Working memory and errors were significantly lowered by 0.3 microgram AVP-(4-8) on the first acquisition session when compared with placebo pretreatment. Thus, AVP-(4-8) improves long-term and short-term memory scores in the HBST, similar to previous results with DGAVP. However, AVP-(4-8) appears twice as potent than DGAVP in improving long-term memory scores in the HBST. The data suggest that the memory modulating property of DGAVP is contained within the amino acid sequence of the AVP-(4-8) peptide.

Analysis of Variance↗
PubMed2026

Proteomic and Phosphoproteomic Signatures Link Molecular Remodeling to Behavioral Outcomes Following Elderberry and DHA Supplementation in Aging Mice.

Background: Aging is a risk factor for Alzheimer's disease and related dementias, which are associated with synaptic dysfunction and cognitive decline. Elderberry (Sambucus spp.) is rich in anthocyanins with antioxidant and anti-inflammatory properties. Docosahexaenoic acid (DHA), an essential fatty acid, plays a key role in neuronal membrane integrity during brain aging. However, it remains unclear whether elderberry and DHA exert overlapping or distinct effects on brain aging and how these relate to molecular signaling. This study aimed to characterize molecular signatures induced by dietary supplementation and to determine their relationships with behavioral outcomes. Methods: 44-week-old male C57BL/6J mice were randomly assigned to control, elderberry, DHA, or combined diets for 12 weeks. Behavioral testing assessed anxiety-like behavior, spatial learning and memory. Brain tissues underwent proteomic and phosphoproteomic profiling and fatty-acid analysis. Data were analyzed using Ingenuity Pathway Analysis to identify enriched pathways, upstream regulators, and functional associations. Results: Elderberry as well as DHA supplementation induced targeted remodeling of the proteome and phosphoproteome, with pathway enrichment involving synaptogenesis, glutamatergic signaling, and long-term potentiation. Upstream-regulator analysis predicted elderberry-associated CDK5 signaling, accompanied by reduced MAPT/Tau phosphorylation at selected sites, whereas DHA supplementation was associated with CAMK-related signaling. DHA supplementation altered fatty-acid composition, increasing the n-3/n-6 ratio. Elderberry reduced anxiety-like behavior and improved target-directed search during the Barnes maze probe test. Molecular signatures were examined in relation to the measured behavioral outcomes. Conclusions: Elderberry and DHA are associated with distinct molecular networks related to synaptic function and behavioral outcomes in the aging male mouse brain. These findings support further investigation of elderberry and DHA as dietary interventions targeting molecular and behavioral features of brain aging.

Animals↗
PubMed2006

Spatial memory activation of the parietal cortex measured with near-infrared spectroscopic imaging in the finger-maze of the Morris water maze analogue for humans.

To assess the cortical regions involved in learning spatial navigation, changes in oxyhemoglobin volume were measured with near-infrared spectroscopy in a task analogous to the Morris water maze. The blindfolded participants (Ps) were allowed to search the area inside the circular ring (20 cm) until they reached a goal (1 cm). The sitting and starting positions were randomly varied across trials, but the goal was in a fixed position so that the Ps could learn the allocentric spatial relationship between the goal and the experimental room. There was a significant sex difference (p < 0.05) in the present task, showing that performance in males was better than that in females. With this task, we measured brain activation in the first training trial, the probe test, and the motor-control trials. In the first trial, dorsolateral prefrontal and parietal cortices were activated. In the probe test, only the dorsolateral prefrontal regions were activated. These results suggest that the parietal cortex is critical for acquisition of spatial memory.

Adult↗
PubMed2004

S-Allylcysteine prevents amyloid-beta peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits.

The effects of S-allylcysteine on oxidative damage and spatial learning and memory deficits produced by an intrahippocampal injection of amyloid-beta peptide 25-35 (Abeta(25-35)) in rats were investigated. The formation of reactive oxygen species, lipid peroxidation and the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were all measured in hippocampus 120 min after Abeta(25-35) injection (1 microl of 100 microM solution), while learning and memory skills were evaluated 2 and 35 days after the infusion of Abeta(25-35) to rats, respectively. Abeta(25-35) increased both reactive oxygen species and lipid peroxidation, whereas pretreatment with S-allylcysteine (300 mg/kg, i.p.) 30 min before peptide injection decreased both of these markers. In addition, Abeta(25-35)-induced incorrect learning responses were prevented in most of trials by S-allylcysteine. In contrast, enzyme activities were found unchanged in all groups tested. Findings of this work: (i) support the participation of reactive oxygen species in Abeta(25-35)-induced hippocampal toxicity and learning deficits; and (ii) suggest that the protective effects of S-allylcysteine were related to its ability to scavenge reactive oxygen species.

Amyloid beta-Peptides↗
PubMed2002

Lateralization of spatial-memory processes: evidence on spatial span, maze learning, and memory for object locations.

Spatial memory is one of the most important cognitive functions in daily life, enabling us to locate objects in our environment or to learn a route or a path. In the present study, we elaborated on the hypothesis that human spatial memory consists of multiple sub-processes, relying on different brain structures. Therefore, 50 patients with an ischemic stroke and 40 healthy participants underwent tests measuring spatial span and maze learning. By means of a computer paradigm the following aspects of memory for object locations were assessed: (1) object location binding; (2) positional memory; (3) a combination of these two aspects. The results clearly showed a double dissociation: the group of patients with an infarct in the left hemisphere (LH) was impaired on object location binding, whereas the group with an infarct in the right hemisphere (RH) was impaired on positional memory. Lesions in the RH resulted also in impairments on maze learning. Moreover, patients with lesions in the posterior part of the parietal or the occipital lobe performed especially worse on spatial-memory tasks. These findings extend the theoretical framework of categorical versus coordinate spatial processing in the human brain and corroborate previous findings on selective aspects of memory for object locations.

Adult↗
PubMed1996

Ethanol- and diazepam-induced cytochrome oxidase activity in mammillary bodies.

This study aims to analyze the effect of the administration of diazepam and alcohol on cytochrome c oxidase activity (COX) in the mammillary bodies (MB) with a quantitative densitometry method. The histochemical reaction of the COX is used as a reflection of energy consumption. Our results show an increase in the COX activity after treatment with diazepam in the different nuclei of MB: medial medial nucleus (MMNm), lateral medial nucleus (MMN1), and lateral nucleus (LMN) of the MB, the MMNm and LMN being significantly more active compared to the MMN1. Furthermore, the consequences of administering these drugs become manifest in spatial learning (water T maze). The performance in a spatial discrimination task did not prove to be impaired.

Animals↗
PubMed2006

N-methyl-D-aspartate receptors in the medial septal area have a role in spatial and emotional learning in the rat.

Cholinergic and GABAergic neurons in the medial septal/vertical limb of the diagonal band of Broca (MS/vDB) area project to the hippocampus and constitute the septohippocampal pathway, which has been implicated in learning and memory. There is also evidence for extrinsic and intrinsic glutamatergic neurons in the MS/vDB, which by regulating septohippocampal neurons can influence hippocampal functions. The potential role of glutamatergic N-methyl-D-aspartate (NMDA) receptors within the MS/vDB for spatial and emotional learning was studied using the water maze and step-through passive avoidance (PA) tasks, which are both hippocampal-dependent. Blockade of septal NMDA receptors by infusion of the competitive NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (0.3-5 microg/rat), infused 15 min prior to training, impaired spatial learning and memory at the 5 microg dose of D-AP5, while doses of 0.3 and 1 microg per rat had no effect. The impairment in spatial learning appears not to be caused by sensorimotor or motivational disturbances, or anxiogenic-like behavior. Thus, d-AP5-treated rats were not impaired in swim performance or visuospatial abilities and spent more time in the open arms of the elevated plus-maze. In the PA task, intraseptal D-AP5 infused 15 min before training impaired retention as examined 24 h after training. This impairment was observed already at the 0.3 microg dose, suggesting that NMDA receptors within the MS/vDB may be more important for emotional than spatial memory. In summary, the present data indicate that changes in septal glutamate transmission and NMDA receptor activity can influence activity-dependent synaptic plasticity in the hippocampus and thereby learning and memory.

Animals↗
PubMed2001

Effects of the uterine environment and neocortical ectopias upon behavior of BXSB-Yaa+ mice.

Between 40-60% of BXSB-Yaa+mice have neocortical ectopias, a genetically based brain anomaly. The presence of ectopias is known to affect several cognitive measures. A second way to affect cognition is by transferring embryos into foreign uteri. These variables were jointly investigated in three experiments. BXSB-Yaa+mouse embryos were transferred into same-strain uteri, or into uteri of hybrid mice. At birth, pups were cross-fostered to hybrid mothers or were reared by their birth mothers. When adult, the mice were given a series of behavioral tests with primary emphasis upon cognitive competence. Across all three studies, mice transferred into hybrid uteri were superior in the Morris maze and the Lashley III maze, and performed more effectively in shuttlebox avoidance learning. They were less effective in the simple water escape task, and the uterus groups did not differ in discrimination learning. Thus, development within a foreign uterus enhanced spatial learning and fear-based conditioning. Ectopic mice were superior to non-ectopics in learning the Morris maze, a finding consistent with prior research using the congenic BXSB-Yaa strain. There were Uterus x Ectopia interactions on a few measures, indicating that, under certain condition, whether the presence of ectopias is beneficial or detrimental is contingent upon the uterine environment within which the organism develops.

Animals↗
PubMed2005

Neurobehavioral changes in metallothionein-null mice prenatally exposed to mercury vapor.

We studied the neurobehavioral effects of prenatal exposure of MT-null and wild-type mice to elemental mercury vapor (Hg0). Pregnant mice of both strains were repeatedly exposed to Hg0 vapor at 0.50 and 0.56 mg/m3 for 6 h/day until the 18th day of gestation. The behavioral effects were evaluated with locomotor activity in the open field, learning ability in the passive avoidance response and spatial learning ability in the Morris water maze at 12 weeks of age. Hg0-exposed MT-null mice showed a significant decrease in total locomotor activity in males, and a learning disability in the passive avoidance response and a retarded acquisition in the Morris water maze in females as compared with the control. In contrast, Hg0-exposed wild-type mice did not differ from controls in the three behavioral measurements. The results indicate that MT-null mice would be more susceptible than wild-type mice to the behavioral neurotoxicity of prenatal Hg0 exposure. Mercury concentrations in the brain of both strains were slightly higher in the exposed group than in the control group, indicating the retention of residual mercury even 12 weeks after the cessation of the exposure. Brain concentrations of mercury were also significantly higher in the exposed-females than exposed-males in either strain. From these results, we suggest that the increased susceptibility of MT-null females to behavioral changes caused by prenatal Hg0 exposure is due to a greater retention of mercury and lack of MT-I,-II in the brain.

Animals↗