Biomedical subjects

Liisa A M Galea

Publications and source records attributed to Liisa A M Galea.

15 recordsLinked to original sources

PubMed2006

Activational levels of androgens influence risk assessment behaviour but do not influence stress-induced suppression in hippocampal cell proliferation in adult male rats.

Adult male, but not female, rats demonstrate a suppression in hippocampal cell proliferation in response to an acute predator odour stress. The present study examined the effect of activational levels of androgens on stress-induced changes in hippocampal cell proliferation and defensive and non-defensive behaviours in adult male rats. Adult male Sprague-Dawley rats were castrated and exposed to trimethylthiazoline (TMT, the main component of fox feces). Androgen status did not significantly affect TMT-induced suppression in hippocampal cell proliferation or expression of defensive burying. However, castrated males did not show an increase in duration of stretch attends (a risk assessment behaviour) in response to TMT. The results of this study suggest that activational levels of androgens in the male rat do not directly regulate the sex difference in stress-induced suppression of hippocampal cell proliferation but do regulate risk assessment behaviour.

Analysis of Variance↗

PubMed2006

First reproductive experience persistently affects spatial reference and working memory in the mother and these effects are not due to pregnancy or 'mothering' alone.

Pregnancy and motherhood are life-altering events that result in a number of hormonal, neural and behavioral changes in the mother. Motherhood has been shown to influence spatial learning and memory performance of the mother. In turn new research has shown that reproductive experience (number of times pregnant and mothered) plays a significant role on spatial learning and memory performance. How long these changes persist after weaning and the role of pregnancy and/or mothering on these changes have yet to be fully investigated. The present study aimed to determine whether enhanced spatial working and/or reference memory in the mother is evident long after weaning and whether these effects are due, in part, to pregnancy or 'mothering' alone. Five groups of age-matched rats: multiparous, primiparous, nulliparous, pregnant-only and sensitized rats were tested approximately 1 month after weaning/pup-exposure, or 55 days after birth, on the spatial working/reference version of the radial arm maze. Results show that regardless of error type (reference or working memory errors), primiparous rats make fewer errors compared to multi- and nulli-parous rats, with a trend to enhanced memory compared to sensitized rats. In addition, pregnant-only rats completed the task on significantly fewer days than primiparous, multiparous, nulliparous and sensitized rats. Clearly the combination of first pregnancy and first mothering experience has a significant impact on hippocampus-dependent learning and memory performance in the mother.

Analysis of Variance↗

PubMed2006

High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression.

Post-partum stress and depression (PPD) have a significant effect on child development and behavior. Depression is associated with hypercortisolism in humans, and the fluctuating levels of hormones, including corticosterone, during pregnancy and the post-partum, may contribute to PPD. The present study was developed to investigate the effects of high-level corticosterone (CORT) post-partum in the mother on postnatal neurogenesis and behavior in the offspring. Sprague-Dawley dams were treated with either CORT (40 mg/kg) or sesame oil injections daily for 26 days beginning the day after giving birth. Dams were tested in the forced swim test (FST) and in the open field test (OFT) on days 24-26 post-partum. Results showed that the dams exposed to CORT expressed "depressive-like" behavior compared to controls, with decreased struggling behavior and increased immobility in the FST. To investigate the effects of treatment on hippocampal postnatal cell proliferation and survival in the offspring, males and females from treated dams were injected with BrdU (50 mg/kg) on postnatal day 21 and perfused either 24 h (cell proliferation) or 21 days (cell survival) later. Furthermore, male and female offspring from each litter were tested in adulthood on various behavioral tests, including the forced swim test, open field test, resistance to capture test and elevated plus maze. Intriguingly, male, but not female, offspring of CORT-treated dams exhibited decreased postnatal cell proliferation in the dentate gyrus. Both male and female offspring of CORT-treated dams showed higher resistance to capture and greater locomotor activity as assessed in the open field test. As high levels of CORT may be a characteristic of stress and/or depression, these findings support a model of 'CORT-induced' post-partum stress and possibly depression and demonstrate that the offspring of affected dams can exhibit changes in postnatal neurogenesis and behavior in adulthood.

Age Factors↗

PubMed2006

Systemic and local administration of estradiol into the prefrontal cortex or hippocampus differentially alters working memory.

The influence of estradiol on learning and memory is dependent on a number of factors. The effects of physiological levels of estradiol on the acquisition of a spatial working memory task mediated by the prefrontal cortex (PFC) and the hippocampus were examined in Experiment 1. Ovariectomized Long-Evans rats received daily injections of estradiol or vehicle were tested on the win-shift version of the radial arm maze. A high dose of estradiol benzoate (5 microg) enhanced acquisition of the task, whereas a low dose of estradiol (0.3 microg) increased the number of errors committed over 17 days of testing. Experiment 2 was conducted to examine site-specific influences of estradiol on spatial working memory in well-trained rats. Saline and estradiol cyclodextrin (0.1 and 0.9 microg) were infused into the prelimbic region of the PFC or dorsal hippocampus 40 min prior to testing on the win-shift task. Infusions of estradiol into both brain areas attenuated saline-infusion disruptions in working memory. Specifically, the higher dose of estradiol facilitated working memory when infused into the PFC, whereas the lower dose of estradiol facilitated performance when infused into the dorsal hippocampus. Moreover, working memory was significantly impaired 24 h after infusions of estradiol into the dorsal hippocampus but not the PFC. These data provide further evidence for the notion that estradiol can dose-dependently alter memory processes and suggest that facilitation or disruptions of working memory by estradiol are site- and time-specific.

Analysis of Variance↗

PubMed2006

Gonadal hormone modulation of hippocampal neurogenesis in the adult.

Gonadal hormones modulate neurogenesis in the dentate gyrus (DG) of adult rodents in complex ways. Estradiol, the most potent estrogen, initially enhances and subsequently suppresses cell proliferation in the dentate gryus of adult female rodents. Much less is known about how estradiol modulates neurogenesis in the adult male rodent; however, recent evidence suggests that estradiol may have a moderate effect on cell proliferation but enhances cell survival in the DG of newly synthesized cells but only when estradiol is administered during a specific stage in the cell maturation cycle in the adult male rodent. Testosterone likely plays a role in adult neurogenesis, although there have been no direct studies to address this. However, pilot studies from our laboratory suggest that testosterone up-regulates cell survival but not cell proliferation in the DG of adult male rats. Progesterone appears to attenuate the estradiol-induced enhancement of cell proliferation. Neurosteroids such as allopregnalone decrease neurogenesis in adult rodents, while pregnancy and motherhood differentially regulate adult neurogenesis in the adult female rodent. Very few studies have investigated the effects of gonadal hormones on male rodents; however, studies have indicated that there is a gender difference in the response to hormone-regulated hippocampal neurogenesis in the adult. Clearly, more work needs to be done to elucidate the effects of gonadal hormones on neurogenesis in the DG of both male and female rodents.

Animals↗

PubMed2006

Hippocampal morphology is differentially affected by reproductive experience in the mother.

Pregnancy and mothering result in a number of hormonal, neurological, and behavioral changes that are necessary to ensure reproductive success. With subsequent reproductive experience (multiparity and mothering), further neurological and behavioral changes may result. Recent research has shown that previous motherhood enhances both hippocampus-dependent learning and memory and long-term potentiation (LTP); together with decreases in hippocampus volumes during pregnancy it is suggested that the hippocampus is affected by pregnancy and/or mothering. The present experiment aimed to investigate the effect of reproductive experience (nulli, primi-, and multiparity and mothering) on dendritic morphology in the CA1 and CA3 regions of the hippocampus. Brains were stained with a modified version of the single-section Golgi impregnation technique, and dendritic length, number of branch points, and spine density was analyzed for apical and basal regions of CA1 and CA3 pyramidal neurons. Primiparity and/or mothering resulted in dendritic remodeling in both the CA1 and CA3 hippocampal regions, and multiparity resulted in enhanced spine density in the basal CA1 region, which was positively correlated with number of male pups in a litter. These findings point to the effect of reproductive experience and offspring on plasticity in the hippocampus, an area not traditionally associated with motherhood.

Analysis of Variance↗

PubMed2006

Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours.

The endocannabinoid system has been shown to regulate both the hypothalamic-pituitary-adrenal (HPA) axis and emotionality. The present experiment was designed to examine whether pharmacological modulation of the endocannabinoid system would affect the suppression of hippocampal cell proliferation and increase in defensive behaviours seen following exposure to predator odour (trimethylthiazoline; TMT) stress. Rats were administered either an endocannabinoid uptake inhibitor (AM404; 2 mg/kg) or a cannabinoid CB1 receptor antagonist (AM251; 5 mg/kg) 30 min prior to exposure to TMT. Exposure to TMT reduced cell proliferation in the dentate gyrus and increased the expression of defensive burying. Administration of AM404 significantly inhibited defensive burying, and attenuated the reduction in cell proliferation in response to TMT exposure. Administration of AM251 alone significantly increased cell proliferation; however, pretreatment with AM251 prevented neither the stress-induced suppression of cell proliferation nor the stress-induced increase in behavioural responses. These results support previous research demonstrating that augmentation of endocannabinoid signalling can suppress stress-responsive systems. They also suggest that endocannabinoids may play a complex role in the regulation of neurogenesis via cell proliferation in the hippocampus.

Aggression↗

PubMed2005

Reproductive experience differentially affects spatial reference and working memory performance in the mother.

The transition to motherhood results in a number of hormonal, neurological, and behavioral changes necessary to ensure offspring survival. Once motherhood is established, further neurological and behavioral changes may result with additional parity and mothering. Recent research has shown that motherhood enhances both hippocampal-dependent learning and memory and oxytocin-induced long-term potentiation, suggesting that the hippocampus is affected by mothering. In turn, degree of maternal behavior, either high or low, has been shown to affect spatial learning and memory performance in adult offspring. The present experiment aimed to investigate the effect of reproductive experience (nulli-, primi-, and multiparity and mothering) and degree of maternal behavior on hippocampus-dependent learning and memory in the mother. Results show that regardless of error type, primiparous rats make fewer errors compared to nulliparous rats, while multiparous rats show a trend towards making fewer errors compared to nulliparous rats. In addition, mothers who spend less time licking and nursing offspring had fewer reference memory errors. Perhaps the enhanced learning and memory in the inexperienced, new mother allows her to effectively acquire the suite of maternal behaviors necessary to ensure offspring survival and achieve reproductive success with subsequent reproductive experience.

Animals↗

PubMed2004

High level estradiol impairs and low level estradiol facilitates non-spatial working memory.

The present study investigated the effect of different doses of estradiol treatment on performance in the non-spatial delayed alternation T-maze a task in which performance is mediated by the integrity of the prefrontal cortex (PFC). Ovariectomized (OVX) female rats were injected with estradiol benzoate (0.3 microg/0.1 ml sesame oil (EB0.3), 5 microg/0.1 ml sesame oil (EB5) or 10 microg/0.1 ml sesame oil (EB 10)) or vehicle (sesame oil, 0.1 ml). Approximately 2 h after each injection, animals were trained daily on the T-maze with an initial delay of 10 s (short delay). Following a month with no treatment animals were re-trained at a 40 s delay (long delay). Days to reach criterion (one error per day for three consecutive days), mean total errors, errors across days, change in performance across training (short subtracted from long delay), and latency to reach goal arm, were scored. At the short delay, there was a weak effect for the low dose of estradiol (EB0.3 low-to-medium physiological) to significantly decrease the number of working memory errors compared to controls. However at the longer delay the higher doses of estradiol EB5 (high physiological) and to a lesser extent EB10 (suupraphysiological) significantly increased the number of working memory errors compared to controls. These data demonstrate the differential effect of estradiol during short and long delays on prefrontal cortex dependent working memory. High levels of estradiol impair PFC-dependent working memory at longer delays, while low level estradiol weakly facilitates PFC-dependent working memory at a shorter delay. These data suggest that estradiol's facilitatory effects on working memory may not be mediated through the PFC, while estradiols inhibitory effects on working memory may be mediated at least in part through the PFC.

Animals↗

PubMed2004

Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects.

Running activity increases cell proliferation and neurogenesis in the dentate gyrus of adult mice. The present experiment was designed to investigate whether the effect of activity on adult neurogenesis is dependent on the time of day (circadian phase) and the amount of activity. Mice received restricted access to a running wheel (0, 1, or 3 hr) at one of three times of day: the middle of the light phase (i.e., when mice are normally inactive), dark onset (i.e., when mice begin their nocturnal activity), and the middle of the dark period (i.e., when mice are in the middle of their active period). Cell proliferation and net neurogenesis were assessed after incorporation of the thymidine analog bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU and neuronal markers. Running activity significantly increased cell proliferation, cell survival, and total number of new neurons only in animals with 3 hr of wheel access during the middle of the dark period. Although activity was positively correlated with increased neurogenesis at all time points, the effects were not statistically significant in animals with wheel access at the beginning of the dark period or during the middle of the light period. These data suggest that the influence of exercise on cell proliferation and neurogenesis is modulated by both circadian phase and the amount of daily exercise, thus providing new insight into the complex relationship between physiological and behavioral factors that can mediate adult neuroplasticity.

Animals↗

PubMed2003

Sex differences in cell proliferation, cell death and defensive behavior following acute predator odor stress in adult rats.

Males show suppressed cell proliferation in the hippocampus in response to acute stress but no studies to date have examined cell proliferation in response to acute stress in females. In the current study, we examined the effects of acute exposure to a predator odor stressor [trimethyl thiazoline (TMT); the main component of fox feces] or a control odor on cell proliferation and cell death in the dentate gyrus and on behavior in adult male and female [intact, ovariectomized (OVX) or OVX+estradiol benzoate (EB)] rats. Further, we examined whether TMT-induced changes in behavior were related to cellular changes. During TMT exposure, rats were injected with the cell synthesis marker bromodeoxyuridine and perfused 24 h later. Acute TMT exposure suppressed both cell proliferation and death in males but not in any group of females. Interestingly, in the OVX females we observed an increase in cell death that was eliminated by EB treatment. Consistent with prior studies, estradiol treatment increased cell proliferation regardless of odor condition. Regardless of sex or hormone treatment, TMT increased defensive behavior, suggesting that the behavioral response to TMT is dissociated from this cellular response. This is the first demonstration of a sex difference in cell proliferation and death in the adult dentate gyrus in response to stress.

Aggression↗

PubMed2002

High levels of estradiol impair spatial performance in the Morris water maze and increase 'depressive-like' behaviors in the female meadow vole.

The present study investigated sex differences and the effect of a high level of estradiol in the female meadow vole on performance in the forced swim test (FST) and the Morris water maze in meadow voles. Female meadow voles were ovariectomized (OVX) and administered either vehicle (sesame oil) or estradiol for 2 days prior to performing the FST. Four days following the FST, all animals were run in the Morris water maze. Results indicated that estradiol-injected female meadow voles showed more 'depressive-like' behaviors in the FST (greater time spent immobile and less time spent swimming) than vehicle-treated female or male meadow voles. In addition, estradiol-treated females had impaired performance (greater latencies and distance swam to reach the hidden platform) than both vehicle-treated female and male meadow voles, consistent with previous data. Despite the fact that estradiol administration increased 'depressive-like' behaviors in the FST and impaired performance in the Morris water maze, there was no correlation between the two behaviors indicating that 'depressive-like' behaviors did not account for the differences seen in spatial performance in the Morris water maze. To our knowledge, this is the first demonstration in rodents indicating that estradiol-mediated changes in behavior in the FST is not indicative of subsequent performance in the Morris water maze.

Animals↗

PubMed2002

Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze.

Previous investigations of estradiol's effects on learning and memory yielded equivocal results. This study was designed to determine whether these inconsistencies were due to dose-dependent effects of estradiol on different memory processes. Ovariectomized female rats were injected daily with estradiol benzoate (EB; 0.32, 1.00, or 5.00 microg) or vehicle. Approximately 3 hr after injection, rats were run on a hippocampus-dependent working/reference memory version of the radial arm maze. Total number of working (WME), reference, and combined working/reference memory errors were scored. Compared with vehicle, 1.00 or 5.00 microg EB (high physiological) impaired performance by increasing the number of WME, whereas 0.32 microg EB (low physiological) facilitated performance by decreasing the number of WME. Taken together, these data demonstrate a dose-dependent effect of EB on working memory.

Animals↗

PubMed2002

Defensive behavior and hippocampal cell proliferation: differential modulation by naltrexone during stress.

The present study investigated the role of endogenous opioids in the expression of defensive behaviors (DBs) and the suppression of cell proliferation (CP) in the dentate gyrus (DG) induced by exposure to predator odor, trimethyl thiazoline (TMT). Adult male rats were injected with either naltrexone (an opioid antagonist, 5 mg/kg) or saline 30 min before exposure to either TMT or a control odor. Behavior was scored for the first 15 min of odor exposure. Bromodeoxyuridine (BrdU, 200 mg/kg) was then injected, and the rats were perfused 1 hr later. Exposure to TMT increased the expression of DBs and suppressed the number of proliferating cells in the DG. Pretreatment with naltrexone attenuated the effects of TMT on DB expression but did not attenuate the effects of TMT on CP. In addition, naltrexone administration suppressed CP in the absence of TMT. These results demonstrate a dissociation between DBs and regulation of CP in the DG.

Animals↗

PubMed1995

Sex differences in the expression and antagonism of swim stress-induced analgesia in deer mice vary with the breeding season.

Swim stress-induced analgesia (SSIA) was examined in photoperiodically induced 'breeding' (reproductive) and 'non-breeding' (non-reproductive) adult male and female deer mice, Peromyscus maniculatus. Nociceptive responses (50 degrees C, hot-plate) of breeding and non-breeding deer mice were determined after either a 1- or 3-min swim in 20 degrees C water. The 1-min swim induced an immediate and relatively short-lasting naloxone (1.0 mg/kg) insensitive 'non-opioid' -mediated SSIA that was antagonized by the N-methyl-D-aspartate (NMDA) antagonist, MK-801 (0.10 mg/kg) in all of the groups of mice except the breeding (reproductive) females. Breeding females displayed a non-opioid analgesia that was insensitive to MK-801. The 3-min swim induced a relatively more prolonged mixed opioid and 'non-opioid' SSIA of which the initial portion was sensitive to antagonism by MK-801 in all groups of the mice except the breeding females, while the latter portion (15 min after swim) was induced by naloxone in all of the groups of mice. Overall, the breeding males displayed greater levels of SSIA than the breeding females, with no consistent sex differences in the non-breeding mice. Within sexes, the breeding males displayed greater levels of opioid and non-opioid SSIA than the non-breeding males, while the non-breeding females displayed greater levels of SSIA than the breeding females. These results show that both sex and reproductive status affect the expression and neurochemical mediation of non-opioid SSIA. These findings also suggest that reproductive females may have an unique or novel hormonally (estrogen) dependent mechanism associated with the expression of SSIA.

Analgesia↗