Biomedical subjects

R B Gibbs

Publications and source records attributed to R B Gibbs.

At least 19 recordsLinked to original sources

PubMed2003

Effects of ageing and long-term hormone replacement on cholinergic neurones in the medial septum and nucleus basalis magnocellularis of ovariectomized rats.

Ovariectomized aged rats, some of which received long-term hormone replacement with oestrogen or oestrogen plus progesterone, were evaluated for the number and size of basal forebrain cholinergic neurones, as well as relative levels of choline acetyltransferase (ChAT) and trkA mRNA, in order to determine whether effects on basal forebrain cholinergic cell survival and function correspond with differences in cognitive performance previously described. The results show that ageing combined with long-term loss of ovarian function produced substantial reductions in the levels of ChAT and trkA mRNA in the medial septum and nucleus basalis magnocellularis, relative to much younger ovariectomized controls. In contrast, no significant effects on the number or size of the cholinergic cells were detected, indicating that loss of ovarian function does not cause a loss of cholinergic neurones with age. Long-term hormone replacement had no apparent effect on the number of ChAT-positive neurones detected, and did not prevent the reductions in ChAT and trkA mRNA associated with ovariectomy and ageing. Collectively, the data suggest that ageing combined with long-term loss of ovarian function has a severe negative impact on basal forebrain cholinergic function, but not on cholinergic cell survival per se.

Acetylcholine↗

PubMed2002

Effects of long-term hormone replacement and of tibolone on choline acetyltransferase and acetylcholinesterase activities in the brains of ovariectomized, cynomologus monkeys.

We examined long-term effects of low and high doses of tibolone, conjugated equine estrogens, and conjugated equine estrogens plus medroxyprogesterone acetate on choline acetyltransferase and acetylcholinesterase activities within different regions of the brain in cynomologus monkeys. All treatments were administered for 2 years. None of the treatments produced significant increases in either choline acetyltransferase or acetylcholinesterase in any of eight brain regions analyzed. In contrast, treatment with conjugated equine estrogens plus medroxyprogesterone acetate, but not conjugated equine estrogens alone, produced significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca compared with untreated controls. Treatment with tibolone also resulted in significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca, and this effect was dose-related. These findings are the first to report the effects of long-term therapies used by postmenopausal women on cholinergic measures in the primate brain. The findings are consistent with recent reports in rats, and suggest that any positive effects of long-term estrogen or hormone replacement therapy on cognitive processes are probably not due to significant effects on choline acetyltransferase or acetylcholinesterase activities.

Acetylcholinesterase↗

PubMed2000

Estrogen replacement does not prevent the loss of choline acetyltransferase-positive cells in the basal forebrain following either neurochemical or mechanical lesions.

Recent studies have shown that estrogen replacement can enhance the functional status of basal forebrain cholinergic neurons. Studies have also shown that estrogen has neuroprotective effects both in vitro and in vivo on a variety of cells and against a variety of insults. The present study examined the ability of estrogen replacement to protect basal forebrain cholinergic neurons from the effects of neurochemical and mechanical injury. Ovariectomized Sprague-Dawley rats received either estrogen replacement or sham surgery, and then received either a unilateral injection of ibotenic acid into the nucleus basalis magnocellularis, or unilateral transection of the fimbria fornix. Cholinergic neurons in the medial septum and nucleus basalis were detected and quantified using immunohistochemical techniques. The data show that neither 3 weeks nor 13 weeks of continuous estrogen replacement prevented the loss of choline acetyltransferase (ChAT)-containing cells in the nucleus basalis following a unilateral injection of ibotenic acid. Likewise, estrogen replacement did not prevent a decrease in ChAT-positive cells detected in the medial septum following unilateral transection of the fimbria fornix. Notably, increased numbers of ChAT-positive cells were detected in the contralateral nucleus basalis, and in the ipsilateral and contralateral medial septum, at 2 weeks following a unilateral injection of ibotenic acid into the nucleus basalis; however, these effects were not related to hormone treatment. These data suggest that estrogen replacement does not protect cholinergic neurons in the medial septum and nucleus basalis from the effects of excitotoxic or mechanical injury.

Animals↗

PubMed2000

Oestrogen and the cholinergic hypothesis: implications for oestrogen replacement therapy in postmenopausal women.

Cholinergic deficits in the basal forebrain, hippocampus and cortex are thought to contribute to the risk and severity of cognitive decline associated with ageing and Alzheimer's disease. Work in our laboratory has demonstrated that in rats, basal forebrain cholinergic neurons are affected by physiological fluctuations in circulating oestrogen and progesterone, and that long-term loss of ovarian function produces decreases in cholinergic parameters and nerve growth factor receptor (trkA) mRNA beyond the effects of normal ageing. Conversely, short-term treatment with oestrogen or oestrogen plus progesterone produces increases in cholinergic parameters and trkA, as well as increases in potassium-stimulated acetylcholine release, that are consistent with an increase in basal forebrain cholinergic function. These findings are consistent with recent studies showing the ability of oestrogen and progesterone replacement to enhance spatial memory and reduce performance deficits associated with hippocampal cholinergic impairment. We hypothesize that similar effects of the ovarian hormones on basal forebrain cholinergic neurons in humans may contribute to the effects of hormone replacement on cognitive processes that have recently been described, and to the ability of oestrogen replacement to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women.

Acetylcholine↗

PubMed2000

Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function.

The effects of different hormone replacement regimens on basal forebrain cholinergic function were examined by measuring changes in choline acetyltransferase activity and high affinity choline uptake in adult, ovariectomized, rats. Increases in choline acetyltransferase activity were detected in the frontal cortex (20. 1%) and olfactory bulbs (30.4%) following two weeks, but not four weeks, of repeated treatment with estrogen plus progesterone. Increases in high affinity choline uptake were detected in the frontal cortex (39.5-55.1%), hippocampus (34.9-48.9%), and olfactory bulbs (29.9%) after two weeks, but not four weeks, of either continuous estrogen administration, repeated progesterone administration, or repeated treatment with estrogen plus progesterone. Repeated administration of estradiol (2-25 microg/250 g body weight) for two or four weeks, and continuous estrogen administration for four weeks and six months, produced no significant changes in choline acetyltransferase activity or high affinity choline uptake in the hippocampus, frontal cortex or olfactory bulbs. Continuous estrogen administration for 13 months produced a significant decrease in high affinity choline uptake across all regions with the largest effect (-28.1%) detected in the hippocampus. The findings demonstrate that short-term treatment with estrogen and/or progesterone can significantly enhance cholinergic function within specific targets of the basal forebrain cholinergic projections. Most important is the fact that the effects varied considerably according to the manner and regimen of hormone replacement and did not persist with prolonged treatment. These findings could have important implications for the effective use of hormone replacement strategies in the prevention and treatment of Alzheimer's disease and age-related cognitive decline in women.

Animals↗

PubMed1999

Treatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain.

Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the effects of acute estrogen and progesterone replacement on relative levels of brain-derived neurotrophic factor (BDNF) mRNA and protein in different regions of the adult rat brain. Adult ovariectomized animals were killed 53 h after receiving estrogen (E53), 53 h after receiving estrogen and 5 h after receiving progesterone (E53P), or 72 h after receiving estrogen and 24 h after receiving progesterone (E72P). Ovariectomized controls were killed 53 and 72 h after receiving vehicle. Tissues from the hippocampus, pyriform cortex, olfactory bulbs, septum, and nucleus basalis/ventral pallidum were dissected. Tissues from the right hemisphere were processed for quantitative RT-PCR analysis of BDNF mRNA, and tissues from the left hemisphere were processed for the detection and quantification of BDNF protein by ELISA. The results demonstrate significant increases in BDNF mRNA in the pyriform cortex of E53- and E53P-treated animals, as well as an increase in BDNF protein in the pyriform cortex of E72P-treated animals, relative to controls. Significant increases in BDNF mRNA were likewise detected in the hippocampus of E53- and E72P-treated animals, but were accompanied by a significant decrease in BDNF protein in the hippocampus of E53P- and E72P-treated animals relative to controls. No significant changes in BDNF mRNA or protein were detected in the olfactory bulbs, frontal cortex, or nucleus basalis/ventral pallidum following hormone treatment; however, an increase in BDNF protein was detected in the septum of E53-treated animals. This may indicate an increase in the retrograde transport of BDNF from the hippocampus to the septum, which could help account for the decrease in BDNF protein detected in the hippocampus following hormone treatment. These findings demonstrate that hormone replacement significantly affects relative levels of BDNF mRNA and protein within specific regions of the brain. These effects may, in turn, contribute to the effects of estrogen replacement on hippocampal connectivity and cognitive processes that have recently been reported.

Age Factors↗

PubMed1999

Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition.

A delayed matching-to-position (DMP) T-maze task was used to examine the effects of estrogen replacement on spatial learning and memory, as well as the ability of estrogen replacement to reduce performance deficits produced by acute systemic and intrahippocampal muscarinic cholinergic inhibition. Two experiments were performed. In Experiment 1, ovariectomized animals were trained to criterion on the DMP task and then tested with increased intertrial delays and following systemic scopolamine administration. The animals then received either continuous estrogen replacement or sham surgery and were retested beginning 10 days later. In Experiment 2, ovariectomized animals received guide cannulae implanted bilaterally into the hippocampus. Half of these animals also began receiving continuous estrogen replacement. Two months later, the animals were trained on the DMP task and then tested with increased intertrial delays and following systemic as well as intrahippocampal scopolamine administration. Animals received the same test battery 8 months later and were then immediately trained on a reversal task. The results indicate that estrogen-treated animals acquired the DMP task at a significantly faster rate than the ovariectomized, non-estrogen-treated controls. In addition, estrogen replacement significantly reduced deficits in DMP performance produced by intrahippocampal, but not systemic, scopolamine administration. This occurred when animals were tested after 3.5 months, as well as after 12 months, of continuous estrogen replacement. No evidence for an effect of estrogen replacement on spatial working memory or reversal learning was detected. These findings demonstrate that estrogen replacement can enhance acquisition of a spatial memory task and reduce performance deficits associated with hippocampal cholinergic impairment.

Analysis of Variance↗

PubMed1998

Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement.

Recent studies suggest that hormone replacement therapy can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that these effects are due, in part, to the ability for estrogen and progesterone to enhance hippocampal function, as well as the functional status of cholinergic projections to the hippocampus and cortex, by influencing the expression of specific neurotrophins and neurotrophin receptors. In the present study, quantitative in situ hybridization techniques were used to determine whether the levels of trkA mRNA in the basal forebrain, and nerve growth factor (NGF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus, are significantly affected by physiological changes in circulating gonadal steroids. Gonadally intact animals were sacrificed at different stages of the estrous cycle and ovariectomized animals were sacrificed at different times following the administration of either estrogen or estrogen plus progesterone. In gonadally intact animals, significant fluctuations in the levels of trkA mRNA in the medial septum (MS), and BDNF mRNA in regions CA1 and CA3/4 of the hippocampus, were detected across the estrous cycle. In animals that received hormone replacement, a significant increase (30.4%) in trkA mRNA was detected in the MS of animals sacrificed 24 h following estrogen administration. Levels of trkA mRNA in the MS declined to control levels over the next 48 h; however, a single injection of progesterone administered 48 h after estradiol appeared to prevent any further decline in trkA mRNA over the next 24 h. In addition, significant increases in BDNF mRNA were detected in the dentate granule cell layer (73.4%), region CA1 (28. 1%), and region CA3/4 (76.9%) of animals sacrificed 53 h after receiving estrogen and 5 h after receiving progesterone. No significant changes in trkA mRNA were detected in the nucleus basalis magnocellularis, and no significant changes in NGF mRNA were detected in the hippocampus. These data demonstrate that levels of trkA mRNA in the MS, and BDNF mRNA in the hippocampus, are affected by physiological changes in the levels of circulating gonadal steroids and are elevated in response to acute hormone replacement. The relevance of these effects to the ability for estrogen replacement to enhance cholinergic activity and hippocampal function, and thereby reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women, is discussed.

Animals↗

PubMed1998

Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function.

Recent studies suggest that women are at greater risk for Alzheimer's disease than men and that estrogen replacement can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that the increased risk for Alzheimer's-related dementia is due, in part, to the loss of ovarian function in postmenopausal women and to the effects that decreased levels of ovarian hormones have on basal forebrain cholinergic function. In the present study, the effects of aging and ovariectomy on cholinergic neurons in the rat basal forebrain were examined to determine (1) whether aging differentially affects cholinergic neurons in the basal forebrain of males vs females, and (2) whether long-term loss of ovarian function produces deficits in basal forebrain cholinergic function beyond those associated with aging and sex. In part I of the study, gonadally intact male and female rats were sacrificed at 13, 19, and 25 months of age and the effects of aging on cholinergic neurons in the medial septum (MS) and nucleus basalis magnocellularis (NBM) were compared. In part II of the study, female rats were ovariectomized at 13 months of age and then sacrificed 3 and 6 months later along with gonadally intact, age-matched controls. Adjacent sections through the MS and NBM were processed for either immunocytochemical detection of choline acetyltransferase (ChAT) and p75NTR-like immunoreactivity or for in situ hybridization detection and quantification of ChAT and trkA mRNA. Results from part I revealed no significant effects of age on the relative size or density of cholinergic neurons in the MS and NBM of gonadally intact animals. Likewise, no significant effects on the relative numbers of cholinergic neurons expressing p75NTR protein were detected. However, a significant decrease in trkA mRNA was detected in the MS of gonadally intact females, but not males, between 13 and 25 months of age. No significant effects of aging on ChAT mRNA were detected. Results from part II revealed significant decreases in both ChAT and trkA mRNA in the MS and NBM of female rats sacrificed 6 months, but not 3 months, following ovariectomy relative to age-matched, gonadally intact controls. Short-term estrogen replacement initiated 6 months following ovariectomy and administered for 3 days prior to sacrifice partially restored ChAT mRNA levels in the MS and trkA mRNA levels in the NBM. These findings suggest that ovarian hormones play a role in maintaining normal levels of ChAT and trkA expression in the MS and NBM. The fact that ChAT mRNA was decreased in the MS and NBM at 6 months following ovariectomy suggests that long-term loss of ovarian function produces a decrease in the functional status of basal forebrain cholinergic neurons projecting to the hippocampus and cortex. In addition, we hypothesize that the decreases in trkA mRNA detected both in the MS as a function of aging, and in the MS and NBM in response to ovariectomy, reflect decreases in the production of high affinity nerve growth factor (NGF) receptors, and a decrease in the responsiveness of the cholinergic neurons to endogenous NGF. This, in turn, may increase the susceptibility of the cholinergic neurons to the effects of aging and disease and thereby contribute to basal forebrain cholinergic decline. We conclude that long-term loss of ovarian function combined with aging has a negative impact on basal forebrain cholinergic neurons. These effects may contribute to the risk and severity of cognitive decline associated with aging and Alzheimer's disease in postmenopausal women.

Aging↗

PubMed1998

Estrogen and basal forebrain cholinergic neurons: implications for brain aging and Alzheimer's disease-related cognitive decline.

Recent studies suggest that estrogen replacement therapy can reduce the risk and severity of Alzheimer's disease (AD)-related dementia in postmenopausal women. Many different mechanisms by which estrogen therapy may help to reduce the risk and severity of AD-related pathophysiology have been proposed. Recent animal studies suggest that one way in which estrogen replacement may help to reduce cognitive deficits associated with aging and AD is by enhancing the functional status of cholinergic projections to the hippocampus and cortex. Here we review the evidence that estrogen is important in the maintenance of cholinergic neurons projecting to the hippocampus and cortex and that estrogen replacement can enhance the functional status of these neurons, as well as reduce cognitive deficits associated with muscarinic cholinergic impairment. Based on these studies, we conclude that, in animals, short-term treatment with physiological levels of estrogen, or estrogen and progesterone, has significant positive effects on cholinergic neurons in the medial septum and nucleus basalis magnocellularis and on their projections to the hippocampus and cortex. We hypothesize that similar effects in humans may help delay the decline in basal forebrain cholinergic function associated with aging and AD and thereby reduce the risk and severity of AD-related dementia in postmenopausal women.

Aged↗

PubMed1998

Estrogen replacement attenuates effects of scopolamine and lorazepam on memory acquisition and retention.

A multiple-trial passive avoidance paradigm was used to examine and compare the ability for estrogen replacement to attenuate learning and memory deficits produced by the muscarinic antagonist scopolamine and the benzodiazepine lorazepam. The multiple-trial paradigm was used in order to distinguish effects on acquisition from effects on retention. Estrogen replacement significantly attenuated a scopolamine-induced deficit on passive avoidance acquisition, but not retention. The ability for estrogen to attenuate the effect of scopolamine on acquisition was observed only when the analysis was limited to animals with serum levels of estradiol <200 pg/ml, suggesting that higher levels of estradiol were ineffective. This observation is consistent with at least one recent study showing dose-related effects of estrogen on ChAT-like immunoreactivity in the basal forebrain and supports the hypothesis that effects of estrogen on basal forebrain cholinergic neurons can help to reduce cognitive deficits associated with cholinergic impairment. Estrogen replacement was also observed to protect against a lorazepam-induced impairment on passive avoidance retention. This effect was observed specifically in animals that received estrogen prior to and during training and was not due to any effect of estrogen on serum levels of lorazepam following acute lorazepam administration. Collectively, these data demonstrate the ability for estrogen replacement to attenuate specific pharmacologically induced impairments in learning and retention and provide additional clues as to potential mechanisms by which estrogen replacement may help to reduce cognitive deficits associated with aging and Alzheimer's disease in postmenopausal women.

Animals↗

PubMed1997

Effects of estrogen on basal forebrain cholinergic neurons vary as a function of dose and duration of treatment.

Studies suggest that estrogen replacement can influence learning and memory processes via effects on cholinergic neurons located in specific regions of the basal forebrain. In the present study, immunocytochemical techniques were used to examine the effects of estrogen on basal forebrain cholinergic neurons as a function of the dose and duration of estrogen treatment. Ovariectomized rats received 2, 10, 25, or 100 microg estradiol every other day for a period of 1, 2, or 4 weeks. Sections through the basal forebrain were then processed for the detection of choline acetyltransferase (ChAT) or the low-affinity nerve growth factor receptor (p75NGFR), and the number of immunoreactive cells in the medial septum (MS), the horizontal limb of the diagonal band of Broca (HDB) and the nucleus basalis magnocellularis (NBM) were counted. The effects of dose and duration of estrogen treatment were evaluated by analysis of variance and individual group means were compared with ovariectomized controls using a two-tailed Dunnets test. Administration of 2, 10, or 25 microg estradiol for 1 week produced a dose-related increase in the number of ChAT-like immunoreactive (IR) cells detected in the MS. Likewise treatment with 10 microg estradiol for 1 week, or with 2 microg estradiol for 2 weeks resulted in a significant increase in the number of ChAT-IR cells detected in the NBM. These effects were not observed following treatment with higher doses of estradiol. Nor were they maintained following repeated administration of estradiol for longer periods of time. In contrast, repeated administration of estradiol for 2 or 4 weeks resulted in significant decreases in the number of p75NGFR-IR cells detected in the MS, with the greatest effects observed following treatment with the higher doses of estradiol for longer periods of time. These findings demonstrate that (1) estrogen replacement produces regionally selective effects on basal forebrain cholinergic neurons which vary as a function of both the dose and duration of estrogen treatment, and (2) estrogen has both short-term and longer-term effects on basal forebrain cholinergic neurons, each of which may contribute to the effects of estrogen on learning and memory process and the development of age- and disease-related cognitive decline.

Analysis of Variance↗

PubMed1997

Nerve growth factor induces Fos-like immunoreactivity within identified cholinergic neurons in the adult rat basal forebrain.

Immunocytochemical techniques were used to examine and compare the effects of intracerebroventricular administration of nerve growth factor (NGF) on Fos expression within identified cholinergic and non-cholinergic neurons located in different regions of the adult rat basal forebrain. Animals were killed 1, 3, 6, and 12 h after receiving NGF (0.5 or 5.0 microg) or vehicle into the left lateral ventricle and sections through the medial septum, diagonal band of Broca, nucleus basalis magnocellularis, and striatum were processed for the combined immunocytochemical detection of Fos and choline acetyltransferase (a marker for cholinergic neurons), or Fos and parvalbumin (a marker for gamma aminobutyric acid (GABA)-containing neurons). NGF produced a significant increase in the percentage of cholinergic neurons containing Fos-like immunoreactivity within all four regions examined. The largest increases were detected in the medial septum (47.8%) and the horizontal limb of the diagonal band of Broca (67.7%). In these areas, NGF-mediated induction of Fos-like immunoreactivity was detected as early as 3 h, peaked at 6 h, and was reduced by 12 h, postinfusion. Small but significant increases in the percentage of cholinergic neurons containing Fos-like immunoreactivity were also detected in the striatum (4.2%) and in the nucleus basalis magnocellularis (19.2%) 3-12 h following administration of the higher dose of NGF. No evidence for an NGF-mediated induction of Fos within parvalbumin-containing neurons was detected in any of the four regions at any of the time-points examined; however, evidence for an NGF-mediated induction of Fos within epithelial cells lining the lateral ventricle was observed. These data demonstrate that NGF induces Fos expression within cholinergic, and not parvalbumin-containing (GABAergic), neurons in the basal forebrain, and furthermore that intracerebroventricular administration of NGF influences the different subgroups of basal forebrain cholinergic neurons to different degrees.

Animals↗

PubMed1997

Effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult rats.

In vivo microdialysis techniques were used to examine the effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult, ovariectomized rats. Estrogen treatment resulted in a significant increase in the percent change in acetylcholine release induced by potassium relative to controls, particularly after prolonged (90 min) exposure to high potassium. The data suggest that estrogen may help to maintain cholinergic function under conditions where cholinergic afferents to the hippocampal formation and cortex are challenged or impaired.

Acetylcholine↗

PubMed1997

Influence of maternal grooming, sex and age on Fos immunoreactivity in the preoptic area of neonatal rats: implications for sexual differentiation.

The medial preoptic area (mPOA) of the hypothalamus contains a sexually dimorphic nucleus (SDN-POA) that is 5-7 times larger in males than females and which contributes to the development and expression of male-specific sex behaviors in adulthood. Aside from a critical role for estrogen, the mechanisms that establish and maintain this sex difference are largely unknown. Differences in the size of the SDN-POA are thought to be related to estrogen-associated effects on programmed cell death (apoptosis) during early neonatal development. The expression of male sex behavior is also influenced by maternal behavior during development. During the postnatal period, the dam grooms the anogenital region of the pups to stimulate urination and defecation; however, male pups are groomed significantly more often than females and this maternal attention influences the expression of normal male sexual behavior in adulthood. Based on these observations, we hypothesized that different amounts of anogenital sensory stimulation might contribute to the sexually dimorphic development of the SDN-POA, specifically by providing for different levels of neuronal activation in the SDN-POA resulting in different degrees of cell death. Two experiments were conducted to test this hypothesis. In the first experiment, male and female rat pups on postnatal day 3 (PN 3) received simulated anogenital grooming with a stiff bristle paint brush. One hour later, the brains were removed and sections through the POA were cut and processed for the immunocytochemical detection of Fos-like immunoreactivity (IR) as an indicator of neuronal activation. In the second experiment, male and female littermates were killed on PN 3, 5, 7 and 12 and the number of Fos-immunoreactive cells and pyknotic cells detected in the SDN-POA were counted and compared. Our data demonstrate that anogenital stimulation on PN 3 results in a rapid induction of Fos-immunoreactive in the POA of both males and females. However, the majority of Fos-immunoreactive cells were located in the ventral POA and were distinctly lacking in the SDN-POA. In experiment 2, again no Fos-immunoreactive cells were detected in the SDN-POA of animals examined on PN 5-12. However, there was an increase in the number of pyknotic cells in the area surrounding and including the SDN-POA of females relative to males at PN 5, 7 and 12. Collectively, the data suggest that (1) anogenital grooming during early postnatal development induces a rapid activation of cells in the ventral mPOA, but not in the SDN-POA of rats, (2) there is a greater incidence of cell death in and around the SDN-POA of females vs. males during neonatal development, particularly toward the end of the hormone-sensitive critical period, and (3) Fos expression does not appear to be correlated with the sexually dimorphic development of, and/or programmed cell death within, the developing SDN-POA.

Aging↗

PubMed1996

Expression of estrogen receptor-like immunoreactivity by different subgroups of basal forebrain cholinergic neurons in gonadectomized male and female rats.

Recent studies have demonstrated that estrogen administration can produce significant increases in relative levels of choline acetyltransferase (ChAT) mRNA and protein in specific regions of the female, but not the male, rat basal forebrain. In the present study immunocytochemical techniques were used to identify and compare relative numbers of cholinergic neurons containing estrogen receptors within the medial septum, horizontal limb of the diagonal band of Broca, nucleus basalis magnocellularis, and striatum of gonadectomized male and female rats to determine whether there are differences in the percentage of cholinergic neurons expressing estrogen receptors which might contribute to the different regional- and sex-specific effects of estrogen which have been described. Counts of choline acetyltransferase-immunoreactive cells revealed significant regional differences in the average number of cholinergic neurons/section; however, no difference between males and females in the numbers of cholinergic neurons in each of the four regions analyzed was observed. Fifty to eighty percent of the cholinergic neurons detected in both males and females contained estrogen receptor-like immunoreactivity. A small but significant difference between males and females was detected with females having slightly more (10.5%) double-labeled cells than males overall. Individual comparisons revealed that significantly more (18-33%) double-labeled cells were detected in the horizontal limb of the diagonal band, but not in the medial septum, nucleus basalis, or striatum of females vs. males. There was also a small but significant regional difference in the percentage of double-labeled cells with the highest percentage (74.2%) detected in the striatum and the lowest percentage (63.4%) detected in the horizontal limb. None of these differences appear to account for the regional- and sex-specific effects of estrogen on cholinergic neurons which have been observed. We conclude that differences in the effects of estrogen on cholinergic neurons in males vs. females and in different subregions of the female basal forebrain are not due to differences in the percentage of cholinergic neurons expressing estrogen receptors.

Animals↗

PubMed1996

Fluctuations in relative levels of choline acetyltransferase mRNA in different regions of the rat basal forebrain across the estrous cycle: effects of estrogen and progesterone.

Quantitative in situ hybridization techniques were used to compare relative cellular levels of choline acetyltransferase (ChAT) mRNA in different regions of the female rat basal forebrain at different stages of the estrous cycle and at different time points after the administration of physiological levels of estrogen and progesterone. Significant fluctuations in relative levels of ChAT mRNA were detected during the course of the estrous cycle. In the medial septum (MS) and striatum, the highest levels of ChAT mRNA were detected on diestrus 1. Fluctuations in the nucleus basalis magnocellularis (NBM) were highly variable, with the highest levels detected on diestrus 2. In ovariectomized animals, significant increases in ChAT mRNA were detected in the MS, NBM, and striatum within 1-3 d after a single administration of estradiol. In addition, the effects of estradiol on ChAT mRNA expression in the NBM and striatum were significantly enhanced by the subsequent administration of progesterone. The magnitude and timing of the effects of steroid replacement were consistent with the magnitude and time course of the fluctuations detected during the course of the estrous cycle. These data demonstrate that estrogen and progesterone can increase basal forebrain levels of ChAT mRNA significantly in specific regions of the rat basal forebrain, that the magnitude and time course of the effects vary between different subpopulations of cholinergic neurons, and that the effects are associated with changes in the functioning of specific basal forebrain cholinergic neurons across the estrous cycle.

Animals↗

PubMed1996

Expression of EGFR-, p75NGFR-, and PSTAIR (cdc2)-like immunoreactivity by proliferating cells in the adult rat hippocampal formation and forebrain.

Immunocytochemical and autoradiographic techniques were used to examine proliferating cells in the adult rat brain along with the expression of specific growth factor receptors and cell cycle proteins. Two hours following an injection of [3H]thymidine ([3H]Thy), dividing cells were detected in the subgranular region of the dentate gyrus and in the subependymal region (SER) extending into the olfactory bulb. Many cells continued to divide over the next 24 h as demonstrated by the ability for thymidine-labeled cells to incorporate bromodeoxyuridine (BrdU); however, the results of BrdU, PSTAIR, and vimentin staining suggest that the majority of the progeny cells detectable by [3H]Thy autoradiography at 3 days and 1 week after injection are postmitotic and at least partially differentiated. Significant numbers of thymidine-labeled cells detected 2 h following thymidine injection in the subgranular region of the dentate gyrus and in the SER of the lateral ventricle stained positively for epidermal growth factor receptor-, vimentin-, and PSTAIR-like immunoreactivity. Significant numbers of thymidine-labeled cells in the SER also stained positively for the low-affinity neurotrophin receptor p75NGFR. No [3H]Thy/p75NGFR-labeled cells were detected in the dentate gyrus. In addition, very few [3H]Thy/PSTAIR- or [3H]Thy/ vimentin-labeled cells were detected in region CA4. These data suggest that proliferating cells located in different regions of the adult brain may not be homogeneous and may be subject to different growth factor regulation.

Animals↗