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J M Juraska

Publications and source records attributed to J M Juraska.

At least 19 recordsLinked to original sources

Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood.

Neuroimaging studies have established that there are losses in the volume of gray matter in certain cortical regions between adolescence and adulthood, with changes in the prefrontal cortex being particularly dramatic. Previous work from our laboratory has demonstrated that cell death can occur as late as the fourth postnatal week in the rat cerebral cortex. The present study examined the possibility that neuronal loss may occur between adolescence and adulthood in the rat prefrontal cortex. Rats of both sexes were examined during adolescence (at day 35) and young adulthood (at day 90). The volume, neuronal number, and glial number of the medial prefrontal cortex (mPFC) were quantified using unbiased stereological techniques. Neurons were lost from the ventral, but not dorsal, mPFC between adolescence and adulthood, suggesting a late wave of apoptosis that was region-specific. This was accompanied by a decrease in the volume of the female ventral mPFC. In contrast to neuron number, the number of glial cells was stable in the ventral mPFC and increased between adolescence and adulthood in the dorsal mPFC. Sex-specific developmental changes in neuron number, glial number, and volume resulted in sex differences in adults that were not seen during adolescence. The loss of neurons at this time may make the peri-adolescent prefrontal cortex particularly susceptible to the influence of environmental factors.

Aging↗

Sexually dimorphic aging of dendritic morphology in CA1 of hippocampus.

During aging, rats of both sexes experience a decline in performance on hippocampal-dependent tasks. Investigations into the neuroanatomical correlates of this functional decline have been conducted almost exclusively in male subjects. In the present study, dendritic spine density in stratum radiatum and complexity of the entire apical dendritic tree were quantified using Golgi-Cox-stained tissue in young (3-5 months) and aged (19-22 months) rats of both sexes. Because both cognitive decline and hippocampal morphology may be influenced by ovarian hormonal state, young adult females were examined during either proestrus or estrus, and aged females were examined in one of two reproductively senescent states: persistent estrus or persistent diestrus. A sex difference in dendritic branching of CA1 pyramidal cells was found among young adults. However, this difference disappeared during aging, due to a reduction in branching with age for males but not for females. Spine density was not influenced by age or sex, nor did ovarian hormone status influence either measure. These results are consistent with our previous findings in the rat medial prefrontal cortex and primary motor cortex and with the human literature, which indicate that age-related atrophy of cognitive brain regions is more severe for males than females.

Aging↗

Tetrachlorodibenzo-p-dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR mice.

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD-induced alterations in spatial learning, we tested male and female AhR-knockout (AhR-/-), heterozygous (AhR+/-) and wild-type (AhR+/+) mice on the RAM. AhR+/- male and female mice were time mated, and treated dams were dosed with 5 microg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR+/+, AhR+/- and AhR-/- mice from TCDD-exposed and unexposed litters were tested on the eight-arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD-exposed female AhR+/- mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra- and infrapyramidal mossy fiber (IIP-MF) field of the hippocampus. None of the other TCDD-exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP-MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR+/- mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.

Animals↗

Androgen receptor expression in the developing male and female rat visual and prefrontal cortex.

Gonadal steroid hormones are known to influence the development of the cerebral cortex of mammals. Steroid hormone action involves hormone binding to cytoplasmic or nuclear receptors, followed by DNA binding and gene transcription. The goals of the present study were twofold: to determine whether androgen receptors are present during development in two known androgen sensitive regions of the rat cerebral cortex, the primary visual cortex (Oc1) and the anterior cingulate/frontal cortex (Cg1/Fr2); and to determine whether androgen receptor (AR) expression in these regions differs between developing males and females. We used immunocytochemistry to detect AR protein on postnatal days 0, 4, and 10, and in situ hybridization to detect AR mRNA on postnatal day 10 in male and female rats. The level of AR expression was specific to the cortical region, with higher AR immunoreactive cell density and more AR mRNA in Oc1 than in Cg1/Fr2. AR immunoreactive cell density increased with age in both regions. Finally, on postnatal day 10, males had a higher AR immunoreactive cell density and more AR mRNA in Oc1 than did females. Thus, the presence of ARs may allow androgens to directly influence the development the cerebral cortex.

Animals↗

Sex differences in mouse cortical thickness are independent of the complement of sex chromosomes.

Although the morphology of the cerebral cortex is known to be sexually dimorphic in several species, to date this difference has not been investigated in mice. The present study is the first to report that the mouse cerebral cortex is thicker in males than in females. We further asked if this sex difference is the result of gonadal hormones, or alternatively is induced by a direct effect of genes encoded on the sex chromosomes. The traditional view of mammalian neural sexual differentiation is that androgens or their metabolites act during early development to masculinize the brain, whereas a feminine brain develops in the relative absence of sex steroids. We used mice in which the testis determination gene Sry was inherited independently from the rest of the Y chromosome to produce XX animals that possessed either ovaries or testes, and XY animals that possessed either testes or ovaries. Thus, the design allowed assessment of the role of sex chromosome genes, independent of gonadal hormones, in the ontogeny of sex differences in the mouse cerebral cortex. When a sex difference was present, mice possessing testes were invariably masculine in the morphology of the cerebral cortex, independent of the complement of their sex chromosomes (XX vs. XY), and mice with ovaries always displayed the feminine phenotype. These data suggest that sex differences in cortical thickness are under the control of gonadal steroids and not sex chromosomal complement. However, it is unclear whether it is the presence of testicular secretions or the absence of ovarian hormones that is responsible for the thicker male cerebral cortex.

Animals↗

Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the morris water maze.

Ovarian steroids have been suggested to aid in preserving cognitive functioning during aging in both humans and other animals. Spatial memory relies heavily on the hippocampus, a structure that is sensitive to the influence of both ovarian hormones and aging. The present study investigated the outcome of ovarian hormone replacement during aging on performance in a spatial version of the Morris water maze. Female rats were ovariectomized at 14 months of age and received one of three types of replacement prior to testing at 16 months: acute estrogen replacement (2 days), chronic estrogen replacement (28 days), or chronic replacement of both estrogen and progesterone (28 days). Control animals, which did not receive replacement hormones, displayed significant overnight forgetting during acquisition of the task. Ovarian hormone replacement, both acute and chronic, prevented forgetting. Previous studies have demonstrated that high levels of ovarian hormones are detrimental to performance of young adult female rats on this task (Warren and Juraska, 1997; Chesler and Juraska, 2000). The current study found an opposite effect during aging: ovarian hormone replacement was beneficial. This suggests that animal models of menopause, aimed at exploring the protective effects of hormone replacement therapy on cognition during human female aging, require the use of aged female animals.

Aging↗

Cell death in the development of the posterior cortex in male and female rats.

Work from our laboratory has shown that adult male rats have 19% more neurons than female rats in the binocular region and 18% more in the monocular region of the primary visual cortex (Reid and Juraska [1992] J Comp Neurol 321:448-455; Nuñez et al., [1999] Soc Neurosci Abstr 25:229). In the current experiment, we investigated whether cell death in male and female rats (postnatal days 2-35) contributes to the formation of these differences. Using stereological techniques, we investigated neuron density along with pyknotic and apoptotic (TdT-mediated deoxyuridine triphosphate nick end-labeled) cell density in the developing posterior cortex (future primary visual cortex). Although no sex differences in neuronal density were found in early development, we observed a differential time course of cell death between the sexes. Consistent with earlier reports, males displayed a rapid rise in cell death, with a peak on day 7 followed by a sharp decline to negligible levels by day 15. Females, however, displayed moderate peaks of cell death on days 7 and 11, with the persistence of low-to-modest levels until day 25. Similar patterns were obtained from both pyknotic and apoptotic cell quantification. Also, a formula was developed to estimate the percentage of cells that die during development and the amount of time a dying cell is visible. This study demonstrates that there is a prolonged period of cell death in the posterior cortex of developing female rats that appears to result in more cell death in females than males. This may be an important mechanism by which the sex difference in adult neuron number is created.

Aging↗

Androgens reduce cell death in the developing rat visual cortex.

We have previously shown that males have more neurons than females in the primary visual cortex, and neonatal androgens play an important role in this difference. Also, we have found that females experience more cell death during development in this region than in males. Therefore, we hypothesized that the neonatal hormone environment directly influences the amount of cell death. In the present experiment, female rats were implanted with dihydrotestosterone (DHT) or estradiol at postnatal day 1. These animals, along with control males and females, were sacrificed on postnatal days 6, 11 and 25. Using unbiased stereology to quantify neuronal and pyknotic cell density, we observed that females implanted with DHT had a similar pattern and proportion of cells dying as control males. Additionally, developmental cell death in females implanted with estradiol was not significantly different than control females. Thus, neonatal androgens have an inhibitory effect on developmental cell death in the rat primary visual cortex.

Animals↗

Neonatal halothane anesthesia affects cortical morphology.

Neonatal cryoanesthesia has recently been documented to affect morphology and behavior after a single exposure [Dev. Brain Res. 111 (1998) 89; Horm. Behav. 37 (2000) 169]. In the current experiment, we investigated the effect of one-time exposure to halothane inhalant anesthesia on neonatal rats of both sexes. Fifteen minutes of exposure on postnatal day one resulted in detectable changes in the volume of the visual cortex at 3 months. Thus, neonatal halothane alters neural development and its effects are observable in the adult rat.

Anesthesia↗

Myelination in the splenium of the corpus callosum in adult male and female rats.

Previous work reported increases in the number of myelinated axons in the splenium of the rat corpus callosum between 25 and 60 days of age. In the present study, we quantified the area occupied by myelinated axons using a light microscopic point counting technique at 60, 120 and 180 days. Myelinated axons increased across these ages (p=0.001). Thus, myelination of the rat corpus callosum persists well into adulthood.

Age Factors↗

Hippocampal anatomy and water maze performance are affected by neonatal cryoanesthesia in rats of both sexes.

There is recent evidence that cryoanesthesia, commonly used during neonatal hormone manipulations (e.g., gonadectomy), has deleterious effects on the morphology of the splenium of the corpus callosum and primary visual cortex in adult rats of both sexes. (Nuñez and Juraska, 1998; Nuñez, Kim, and Juraska, 1998). In the present study, the effect of neonatal cryoanesthesia on the morphology of the hippocampus and dentate gyrus and on performance in the Morris water maze was investigated. Cold exposure for as brief as 30 min (5 degrees C) on Postnatal Day 1 resulted in a significant decrease in the volume of the hippocampus and in brain weight of adults. Performance on the water maze was also impaired in cold-exposed animals. This study indicates that not only morphology but also behavioral performance in adulthood are affected by neonatal cryoanesthesia.

Adjuvants, Anesthesia↗

Acute administration of estrogen and progesterone impairs the acquisition of the spatial morris water maze in ovariectomized rats.

Although several markers of synaptic efficacy are enhanced during proestrus, spatial water maze performance is impaired. Because levels of both estrogen and progesterone are elevated in proestrus, the nature of their individual and combined effects on spatial learning was examined. Long-Evans hooded rats were ovariectomized postpubertally and pretrained on a water maze with a visible platform (nonspatial). Following pretraining, rats were administered estrogen (5 microg sc) or oil 48 and 24 h prior to testing and progesterone (500 microg sc) or oil 4 h prior to testing. Rats were tested on a water maze in a different room with a submerged platform (spatial) for 16 trials with random start location in a single testing day. Latency and path length to the target platform were significantly greater in estrogen plus progesterone-treated animals than in controls. Neither estrogen nor progesterone alone significantly impaired performance relative to controls on either measure. Swim speed was not significantly affected by any of the hormone treatments. Performance on a nonspatial cue task was not significantly altered by ovarian steroids. Thus, the combination of estrogen and progesterone produces deficits in the acquisition of the Morris water maze that may be specific to spatial reference memory. These deficits could be due to hormonal influences on extrahippocampal structures or to detrimental effects on behavior resulting from the increased synaptic activity intrinsic to the hippocampus proper.

Animals↗

Sex differences and estropausal phase effects on water maze performance in aged rats.

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.

Aging↗

Sex differences in thermal nociception and morphine antinociception in rodents depend on genotype.

It has been appreciated for some time that the sexes can differ in their sensitivity to pain and its inhibition. Both the human and rodent literatures remain quite contentious, with many investigators failing to observe sex differences that others document clearly. Recent data from our laboratory have pointed to an interaction between sex and genotype in rodents, such that sex differences are observed in some strains but not others. However, these studies employed inbred mouse strains and are thus not directly relevant to existing data. We presently examined whether the observation of statistically significant sex differences in nociception and morphine antinociception might depend on the particular outbred rodent population chosen for study. Rats of both sexes and three common outbred strains were obtained from three suppliers (Long Evans, Simonsen; Sprague Dawley, Harlan; Wistar Kyoto, Taconic) and tested for nociceptive sensitivity on the 49 degrees C tail-withdrawal assay, and antinociception following morphine (1-10mg/kg, i.p.). In further studies, three outbred populations of mice (CD-1, Harlan; Swiss Webster, Harlan; Swiss Webster, Simonsen) were bred in our vivarium for several generations and tested for tail-withdrawal sensitivity and morphine antinociception (1-20male, and no significant difference. In a separate study in which the estrous cycle was tracked in female mice, we found evidence for an interaction between genotype and estrous phase relevant to morphine antinociception. However, estrous cyclicity did not explain the observed sex differences. These data are discussed with respect to the existing sex difference and pain literature, and also as they pertain to future investigations of these phenomena.

Analgesics, Opioid↗

Neonatal cryoanesthesia affects the morphology of the visual cortex in the adult rat.

Hypothermia is often employed as an anesthetic for manipulations of neonatal animals. We previously reported [J. Nuñez, J.M. Juraska, The effect of neonatal cryoanesthesia on the gross size of the splenium of the corpus callosum, Dev. Psychobiol. 30 (1997) 259; J. Nuñez, J.M. Juraska, The size of the splenium of the rat corpus callosum: influence of hormones, sex ratio and neonatal cryoanesthesia, Dev. Psychobiol., in press.] that the area of the splenium of the adult rat corpus callosum negatively correlated with the time neonatal pups spent in the cold. In the present study, we examined the effect of exposure to neonatal hypothermia (0, 15, 30 and 60 min at 4 degreesC, within 2 h of birth) on the thickness and volume of the binocular (Oc1B) and monocular (Oc1M) fields of the adult rat visual cortex. The number of neurons and glia in layer 2/3 in these areas was also assessed in the 0 and 60 min cold-exposed groups. Cryoanesthesia significantly decreased the length, thickness, volume and number of neurons and glia in both Oc1M and Oc1B. We also observed significant effects of cold exposure on the thickness of individual cortical layers, with some layers affected more than others after differential exposure times. Sex differences (males greater than females) were observed in a number of measures after varying amounts of time in cold and in the absence of cold exposure, in confirmation of previous work from our lab [S.N.M. Reid, J.M. Juraska, Sex differences in the gross size of the rat neocortex, J. Comp. Neurol. 321 (1992) 442-447; S.N.M. Reid, J.M. Juraska, Sex differences in neuron number in the binocular area of the rat visual cortex, J. Comp. Neurol. 321 (1992) 448-455.]. The present study points to the potential confound of using cryoanesthesia on neonatal animals to study cortical structure or function.

Aging↗

The size of the splenium of the rat corpus callosum: influence of hormones, sex ratio, and neonatal cryoanesthesia.

The splenium (posterior 1/5) of the corpus callosum is sexually dimorphic in the adult rat brain. In the present study we examined the role of developmental hormones and cryoanesthesia (which is normally used during the performance of neonatal hormone manipulations) on the gross size of the splenium in male and female rats. There was a sex difference in splenial size (male > female) among nonhormonally manipulated animals, p = .0007. While neonatal castration was ineffective in altering the size of the male splenium, testosterone injections in females were found to increase the size of the splenium relative to oil-injected females, p = .05. The effect of developmental testosterone was further observed: Sex ratio (males to females) of the litter correlated with splenial area in females, r = .55, p = .03. Duration of cryoanesthesia negatively correlated with splenial area in males, r = -.81, p = .03, with a similar trend in females.

Animals↗