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2.  Neuroprotective effects of Estrogen Therapy for Cognitive and Neurobiological Profiles of Monkey Models of Menopause 
American journal of primatology  2009;71(9):794-801.
Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes.
PMCID: PMC2847862  PMID: 19475542
monkeys; hormones; menopause; neurobiology; memory
3.  Women’s cognitive health special edition 
Age  2009;31(3):189-190.
PMCID: PMC2734242  PMID: 19277900
4.  Effects of Two Years of Conjugated Equine Estrogens on Cholinergic Neurons in Young and Middle-Aged Ovariectomized Monkeys 
Brain research  2009;1264:13-23.
The effect of estrogen on the number and size of cholinergic neurons in the basal forebrain was examined in surgically menopausal young and middle-aged cynomolgus monkeys. Young and middle-aged female monkeys were ovariectomized and treated with conjugated equine estrogens (Premarin) at doses that are equivalent to those currently prescribed to postmenopausal women. In the medial septum/diagonal band (MS/DB), no effect of treatment with Premarin was observed in the cholinergic neurons in either ovariectomized young or middle-aged monkeys. However, the number and size of cholinergic neurons in the MS/DB of middle-aged monkeys was greater than that in the young monkeys. In the nucleus basalis of Meynert (NBM) of middle-aged monkeys, the number of cholinergic neurons in the intermediate region (Ch4i) was greater in Premarin-treated monkeys as compared to controls and numbers of neurons in this region were greater at higher levels of estrogen. No effects of estrogen were observed in other NBM regions in the middle-aged monkeys and the size of cholinergic neurons was unaffected by Premarin. These findings suggest that treatment with Premarin has selective beneficial effects on cholinergic neurons in the basal forebrain but that these effects are both age and region specific.
PMCID: PMC2783493  PMID: 19401167
Premarin; nucleus basalis; medial septum; diagonal band; ovariectomy; stereology
5.  Executive Function and Attention are Preserved in Older Surgically-Menopausal Monkeys Receiving Estrogen or Estrogen plus Progesterone 
Animal models of menopause have been used to further define the cognitive processes that respond to hormone therapy and to investigate parameters that may influence the cognitive effects of estrogen. Many investigations in animals have focused on memory; however, the effects of hormone therapy on executive function and attention processes have not been well studied. Thus, the purpose of this set of investigations was to assess the effects of estrogen therapy alone or with progesterone on executive and attention processes in middle-aged ovariectomized monkeys. Monkeys were preoperatively trained on a modified version of the Wisconsin Card Sort Task and on a visual cued reaction time task. Hormone therapy was initiated at the time of ovariectomy and cognitive function was reassessed at 2, 12 and 24 weeks postoperatively. Relative to monkeys receiving either of the estrogen therapies, monkeys receiving placebo were impaired in their ability to shift a cognitive set in the Wisconsin Card Sort Task and were impaired in shifting visuospatial attention in the visual cued reaction time task. Our findings are consistent with clinical studies that indicate that hormone therapy can improve executive function and attention processes in postmenopausal women.
PMCID: PMC2744632  PMID: 19692611
ovariectomy; hormone therapy; Wisconsin card sort; visuospatial attention; set-shifting; nonhuman primate
6.  Differential Effects on Visual and Spatial Recognition Memory of a Novel Hormone Therapy Regimen of Estrogen Alone or Combined with Progesterone in Older Surgically Menopausal Monkeys 
Neuroscience  2008;154(4):1205-1217.
Building upon our initial studies in young adult surgically menopausal monkeys, this study examined the effects of a novel schedule of administration of estradiol therapy alone, or in combination with progesterone, on visual and spatial recognition memory in older monkeys. Monkeys were preoperatively trained on a delayed matching-to-sample task and a delayed response task. At the time of ovariectomy, monkeys began their hormonal treatments and were cognitively assessed at 2, 12 and 24 weeks following treatment initiation. A schedule of hormone administration was used that closely modeled the normal fluctuations of hormones during the course of a normal primate menstrual cycle. Monkeys receiving placebo had lower levels of accuracy than monkeys receiving estrogen therapies on the delayed matching-to-sample task that were not apparent until 12 weeks following initiation of therapy and were no longer detected at the 24-week assessment. There was no effect of hormone therapy on accuracy in the delayed response task at any of the postoperative assessments. In both tasks, monkeys treated with estrogen plus progesterone had longer choice response latencies, especially on trials in which they made errors; however these effects did not influence accuracy measures in these animals. Our findings indicate that visual recognition ability may be more sensitive than spatial recognition memory to this novel hormone therapy regimen, that treatment with estradiol plus progesterone was equivalent to that of estradiol alone, and that neither therapy had significant negative impact on memory profiles.
PMCID: PMC2662767  PMID: 18554815
nonhuman primates; ovariectomy; postmenopausal; delayed matching-to-sample; delayed response
7.  Calorie Restriction Reduces the Influence of Glucoregulatory Dysfunction on Regional Brain Volume in Aged Rhesus Monkeys 
Diabetes  2012;61(5):1036-1042.
Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19–31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.
PMCID: PMC3331743  PMID: 22415875
8.  Mentoring for women and underrepresented minority faculty and students: experience at two institutions of higher education. 
Women and minority faculty and students are seriously underrepresented in university and academic healthcare institutions. The role of mentoring has been identified as one of the significant factors in addressing this underrepresentation. We have described the mentoring efforts at two institutions of higher learning in assisting women and minority students and faculty in being accomplished in their academic pursuits. One-hundred-thirty students and >50 women and minority faculty have participated in the mentoring programs described. The number of participants has increased dramatically over the years and continues to evolve positively. These programs appear to be quite successful in the short term. Further evaluation of measurable outcomes will be necessary to fully determine their true impact. The mentoring models for women and underrepresented minority faculty and students at Creighton University Health Sciences Schools and Wake Forest University School of Medicine will serve as a guide for other Health Sciences Schools.
PMCID: PMC2569723  PMID: 17019912
9.  Functional and neurobiological similarities of aging in monkeys and humans 
Age  1997;20(1):29-44.
Aging in humans may be accompanied by alterations in several functional abilities. However, there is a great deal of individual variability in the functions that may be altered with age within and across aged people. One potential source of age-related behavioral variation may lie in a differential vulnerability of neurobiological systems to the aging process in particular individuals. Aged monkeys demonstrate behavioral and brain alterations that have many parallels with those observed in aged humans and are valuable animal models in which to investigate the interrelationships between age, behavior and neurobiological measures. This review outlines the similarities of functional and neurobiological aging in monkeys and humans, notes the variability that exists in both behavioral and neural systems in aging, and identifies some of the areas of aging that are in need of further investigation.
PMCID: PMC3456079  PMID: 23604289
monkeys; aging; learning; memory; attention; motor skills; neurotransmitters; morphology; pharmacology

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