James Herndon

Emory University | EU · Department of Psychology

With the ultimate goal of developing a more representative animal model of Alzheimer's disease (AD), two female amyloid-β-(Aβ) precursor protein-transgenic (APPtg) rhesus monkeys were generated by lentiviral transduction of the APP gene into rhesus oocytes, followed by in vitro fertilization and embryo transfer. The APP-transgene included the AD-as...

Background Diffusion MRI (dMRI) data acquisition protocols are well-established on modern high-field clinical scanners for human studies. However, these protocols are not suitable for the chimpanzee (or other large-brained mammals) because of its substantial difference in head geometry and brain volume compared with humans. Therefore, an optimal dM...

Executive function (EF) is a complex construct that reflects multiple higher-order cognitive processes such as planning, updating, inhibiting and set-shifting. Decline in these functions is a hallmark of cognitive ageing in humans, and age differences and changes in EF correlate with age-related differences and changes in association cortices, part...

Background: Parents of children with Autism Spectrum Disorder (ASD) face unique challenges in caregiving that threaten their ability to take optimal care of themselves and their children. Numerous studies have investigated the stress experienced by parents of children with ASD, but fewer have aimed to enable parents to better cope with the challeng...

Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene t...

Longitudinal cerebral metabolite changes in pig-tailed macaques inoculated with the simian immunodeficiency virus SIVsmmFGb were evaluated with in vivo proton MRS at 3 T. Blood sample collection, and MRS were carried out before and 2, 4, 8, 12, 16, 20, and 24 weeks after SIV inoculation. Significant reduction of N-acetylaspartate (NAA)/creatine (Cr...

Abstract Magnetization transfer (MT) imaging has been explored in prior studies of HIV patients and showed the potential capacity to assess brain injury after HIV infection. In the present study, adult pig-tailed macaques were infected with a highly neuropathogenic virus SIVsmmFGb. MT imaging was exploited to examine the monkey brains before simian...

Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and white matter over the adult lifespan. However, these...

In 2008, clinical observations in our colony of sooty mangabeys (Cercocebus atys) suggested a high frequency of type 2 diabetes. Postmortem studies of diabetic animals revealed dense amyloid deposits in pancreatic islets. To investigate these findings, we screened our colony (97 male mangabeys; 99 female mangabeys) for the disease from 2008 to 2012...

Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50–60 % and the rhesus living 35–40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might exp...

Aging of the optic nerve can result in reduced visual sensitivity or vision loss. Normal optic nerve aging has been investigated previously in tissue specimens but poorly explored in vivo. In the present study, the normal aging of optic nerve was evaluated by diffusion tensor imaging (DTI) in non-human primates. Adult female rhesus monkeys at the a...

The sooty mangabey is a vulnerable West African species that naturally harbors simian immunodeficiency virus (SIV) without pathological symptoms. We present normative hematology and serum chemistry values for this species. Hematology analytes from 136 females and 96 males and serum chemistry analytes from 57 females and 26 males were studied. Value...

Ovarian cycling continues to similar ages in women and chimpanzees yet our nearest living cousins become decrepit during their fertile years and rarely outlive them. Given the importance of estrogen in maintaining physiological systems aside from fertility, similar ovarian aging in humans and chimpanzees combined with somatic aging differences indi...

Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of...

DNA damage and oxidative stress-related genes verified by RT-PCR. (XLSX)

Angiogenesis & vascular remodelling-related genes verified by RT-PCR. (XLSX)

Metabolism & cellular energy-related genes verified by RT-PCR. (XLSX)

CNS physiology and system homeostasis-related genes verified by RT-PCR. (XLSX)

Immune and inflammatory response-related genes verified by RT-PCR. (XLSX)

Embryonic development& CNS remodelling-related genes verified by RT-PCR. (XLSX)

Neurogenesis & synaptic plasticity-related genes verified by RT-PCR. (XLSX)

Apoptosis & cell death-related genes verified by RT-PCR. (XLSX)

Wound healing and scar formation-related genes verified by RT-PCR. (XLSX)

Menopause in women occurs at mid-life. Chimpanzees, in contrast, continue to display cycles of menstrual bleeding and genital swelling, suggestive of ovulation, until near their maximum life span of about 60 years. Because ovulation was not confirmed hormonally, however, the age at which chimpanzees experience menopause has remained uncertain. In t...

The Simian immunodeficiency virus (SIV) infected macaque model exhibits neuropathological symptoms similar to those of HIV(+) patients, and is ideal for studying cognitive impairment and neuropathological sequelae of disease in repeated measurements. The aim of this study is to use Diffusion Tensor Imaging (DTI) and perfusion MRI to longitudinally...

Although all multicellular organisms undergo structural and functional deterioration with age, senescence is not a uniform process. Rather, each organism experiences a constellation of changes that reflect the heterogeneous effects of age on molecules, cells, organs and systems, an idiosyncratic pattern that we refer to as mosaic aging. Varying gen...

Women experience more years of vigorous life after ovulation has ceased than do females of other primate species. Is this an epiphenomenon of the greater life expectancy humans have enjoyed in the past century or so, or is long post-menopausal survival the result of an evolutionary selection process? Recent research implies the latter: Long post-me...

This issue of Gerontology includes a response by van Bodegom et al. to Herndon's recent article on the implications of the grandmother hypothesis for studies of aging and cognition. Although this hypothesis will doubtlessly continue to stimulate discussion, we focus here on our contention that human and non-human primate life histories have evolved...

In female squirrel monkeys (Saimiri sciureus), the reproductive period normally extends from approximately 2.5 years to the mid-teens. In the present study, we examined the age-associated cytological changes in the ovaries of 24 squirrel monkeys ranging in age from newborn to approximately 20 years. We found a significant, age-related decline in th...

Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys wer...

Heart disease is common in both humans and chimpanzees, manifesting typically as sudden cardiac arrest or progressive heart failure. Surprisingly, although chimpanzees are our closest evolutionary relatives, the major cause of heart disease is different in the two species. Histopathology data of affected chimpanzee hearts from two primate centers,...

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia....

A gradual alteration in the mechanisms underlying reproduction and fertility characterizes the aging process in human females. These changes culminate in menopause, conventionally defined as a cessation of menstrual cycles that marks the end of reproductive capacity. In fact, a central and defining event in menopause is the discontinuation of ovula...

A long postreproductive lifespan may distinguish women from all other female primates. A long-held consensus among reproductive scientists has been that our closest living relative, the chimpanzee (Pan troglodytes), experiences menstrual cycles until death. However, a recent study of biannual assessments of gonadotropins, but lacking observations o...

Little is known about the effects of the menstrual cycle on brain activity in primates. Here, we use 18F-fluorodeoxyglucose positron emission tomography to monitor changes in resting brain glucose metabolism across the menstrual cycle in female rhesus monkeys. Results showed greater activity in right lateral orbitofrontal cortex, a region involved...

Aged rats recover poorly after unilateral stroke, whereas young rats recover readily possibly with the help from the contralateral, healthy hemisphere. In this study we asked whether anomalous, age-related changes in the transcriptional activity in the brains of aged rats could be one underlying factor contributing to reduced functional recovery. W...

Age-related brain injuries, including stroke, are a major cause of physical and mental disabilities. Therefore, studying the basic mechanism underlying functional recovery after brain stroke in aged subjects is of considerable clinical interest. This review summarizes the effects of age on recovery after stroke in an animal model, with emphasis on...

We used proteomics to identify regulated proteins following cerebral ischemia in a rat model. Young rats were subjected to reversible middle cerebral artery (MCA) occlusion and proteins were extracted from the peri-infarcted and the corresponding contralateral area at days 3 and 14 postischemia. Proteins were analyzed by two-dimensional polyacrylam...

Fluctuations of ovarian hormones across the menstrual cycle influence a variety of social and cognitive behaviors in primates. For example, female rhesus monkeys exhibit heightened interest for males and increased agonistic interactions with other females during periods of high estrogen levels. In the present study, we hypothesized that females' pr...

Studies of age-related changes in motor function in nonhuman primates have been based exclusively on unimanual motor tasks. In this study, we examined whether aging affects bimanual motor coordination in the monkey model. In addition, we compared performance of ovariectomized and intact females on the task, to examine whether estrogen deficiency im...

As our understanding of age-related cognitive decline advances, studies are now focusing on identification of those areas of cognitive function that undergo the first changes with age. In the present study, in order to determine whether executive function is sensitive to the aging process, we assessed the performance of 16 monkeys of middle-age (12...

Declines in fine motor skills and cognitive function are well known features of human aging. Yet, the relationship between age-related impairments in motor and cognitive function remains unclear. Rhesus monkeys, like humans, show marked decline in cognitive and fine motor function with age and are excellent models to investigate potential interacti...

Here we investigate the effect of viremia and the influence of HAART on the frequency and quality of HIVspecfic T cells in an adolescent/young adult cohort. Measurements of viral loads and the magnitude and quality of antiviral cellular immune responses were performed on 14 HAART-naive and 8 treated HIV-1-infected adolescents. Cross-sectional corre...

Among the most effective vaccine candidates tested in the simian immunodeficiency virus (SIV)/macaque system, live attenuated viruses have been shown to provide the best protection from challenge. To investigate if preimmunization would increase the level of protection afforded by live attenuated SIVmac239Deltanef (Deltanef), macaques were given tw...

Functional assessment of the prefrontal cortices in the non-human primate began with the seminal work of Jacobsen in the 1930s. However, despite nearly 70 years of research, the precise nature of the cognitive function of this region remains unclear. One factor that has limited progress in this endeavor has been the lack of behavioral tasks that pa...

Functional assessment of the prefrontal cortices in the non-human primate began with the seminal work of Jacobsen in the 1930s. However, despite nearly 70 years of research, the precise nature of the cognitive function of this region remains unclear. One factor that has limited progress in this endeavor has been the lack of behavioral tasks that pa...

Normal aging is associated with impairments in learning and memory and motor function. One viable hypothesis is that these changes reflect an age-related decrease in brain plasticity. The aim of the present study was to identify age-related changes in the time course of expression of the axonal growth associated protein 43 (GAP-43) in a rat model o...

The "frontal aging hypothesis" has been proposed by many researchers suggesting that the earliest and most severe age-related changes in the cortex occur in the frontal lobes. Two of these changes include decreases in cognitive functions mediated by the prefrontal cortex (PFC) and significant decreases in norepinephrine (NE) and dopamine (DA). To i...

The nigrostriatal system is critical for fine motor function and its deterioration during aging is thought to underlie the decline in fine manual ability of old persons. Because estrogen has a neuroprotective effect on this system, one might expect women's motor function to be less vulnerable to the detrimental effects of aging than that of men. We...

Here, we evaluate the T cell responses raised by our HIV-1 clade B DNA/MVA vaccine for recognition of a HIV-1 circulating recombinant form (CRF) AG Gag sequence (CRF-02). The cross-clade activity for the AG sequence was better conserved for CD8 than CD4 T cells. CD8 T cells exhibited 75% conservation for height and 83% conservation for breadth, whe...

The authors tested 90 rhesus monkeys (Macaca mulatta) on a task of spatial memory, the spatial Delayed Recognition Span Test. The results showed that performance declined significantly with age, males had greater scores than females, and the rate of apparent decline with age was greater in males than in females. Both working and reference memory de...

One of the unknowns faced by an HIV/AIDS vaccine is the ability of a single clade vaccine to protect against the multiple genetic subtypes and recombinant forms of HIV-1 present in the current pandemic. Here, we use a macaque model to investigate the ability of our clade B vaccine that consists of DNA priming and modified vaccinia Ankara (MVA) viru...

Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we report studies on the development of the DNA component for a DNA/MVA HIV vaccine for humans. Sp...

Functions supported by the frontal lobes are particularly sensitive to the detrimental effects of aging. Recent studies on postmenopausal women find that estrogen replacement therapy benefits performance on tasks dependent on the frontal lobes. To determine whether estrogen has a similar influence in a rhesus monkey model of menopause, we tested fi...

Recently, a simian/human immunodeficiency virus (SHIV) vaccine consisting of priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia Ankara (rMVA) has successfully controlled a virulent SHIV challenge in a macaque model. In this, and the accompanying paper, we report on the construction and...

Infection of pig-tailed macaques with the simian immunodeficiency virus (SIV) isolate SIVsmmFGb frequently results in SIV encephalitis (SIVE) in addition to immunodeficiency and acquired immune deficiency syndrome. We used in situ hybridization to quantitate the number of SIV-infected cells in brain parenchyma, choroid plexus, and meninges from 17...

Estrogen deficiency following ovariectomy or menopause increases the risk of developing diseases such as osteoporosis and may also lead to memory impairment. Although estrogen replacement therapy (ERT) alleviates many symptoms associated with estrogen loss, it is not clear whether it also benefits cognitive function. The effect of estrogens upon co...

Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by complementing antiviral cellular responses with Env antibodies. We tested this concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to macaques being primed at weeks 0 and 8 with SHIV 89.6 Gag-Pol-Env DNA and boosted at week 24 with SHIV-89.6 Gag-...

To examine the relationship of ocular components to refraction throughout the adult life span of the rhesus monkey (Macaca mulatta). Cycloplegic retinoscopy, A-scan ultrasonography, slit lamp examination, indirect ophthalmoscopy, and keratometry were performed in a cross-sectional study of 111 monkeys, aged 5 to 31 years. Lens thickness and anterio...

Aging is characterized by a progressive deterioration of motor function related to dysfunctions of the nigrostriatal system. Because estrogen has been reported to protect dopaminergic neurons and to improve the motor deficits associated with Parkinson's disease, we hypothesized that it would partially reverse the age-related decline of motor functi...

Understanding the nature of changes in cognition with aging has increased in importance as the number of individuals over the age of 65 years grows. To date, studies have demonstrated that age-related changes occur most extensively in the cognitive domains of memory and executive function. Whereas a large number of studies have been conducted about...

In a recent vaccine trial, we showed efficient control of a virulent simian-human immunodeficiency virus SHIV-89.6P challenge by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env- expressing recombinant-modified vaccinia virus Ankara. Here we show that long-term control has been associated with slowly declining levels of vir...

Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (DNA/MVA) vaccine. Here we evaluate the ability of the MVA component of this...

Cellular immune responses against epitopes in conserved Gag and Pol sequences of human immunodeficiency virus type 1 have become popular targets for candidate AIDS vaccines. Recently, we used a simian-human immunodeficiency virus model (SHIV 89.6P) with macaques to demonstrate the control of a pathogenic mucosal challenge by priming with Gag-Pol-En...

Estrogen replacement therapy (ERT) alleviates many postmenopausal symptoms but whether it also benefits cognitive function remains controversial. Further, since estrogen increases the risk of breast and uterine cancers, a new class of compounds, called selective estrogen receptor modulators (SERMs) is being considered as possible alternative to ERT...

Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here, we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster has controlled a highly pathogenic immunodeficiency virus challenge in a Rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed...

Nonhuman primates are indispensable for the study of aging processes. Like other animals, they permit us to observe the effects of age in the absence of the confounds inherent in studies of human beings. Additionally, because they are phylogenetically close to humans and possess certain uniquely primate morphological, endocrine, behavioral, and cog...

Findings are inconsistent regarding whether women's cognitive performance fluctuates across phases of the menstrual cycle, but differences in methodology and the use of reported cycle phase rather than precise hormonal measures may underlie these disparities. Studies in monkeys may help resolve these discrepant findings, since hormonal status can b...

Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed multi...

Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed multi...

Hematologic and blood biochemical variables are of great importance in medical and veterinary practice. In addition, these analytes may have significance as potential biomarkers of aging. Previous reports on normative values of these variables in the chimpanzees are based on cross-sectional studies that did not include individuals of advanced age....

Chimpanzees are susceptible to infection with human immunodeficiency virus (HIV)—1; however, infected animals usually maintain normal numbers of CD4+ T lymphocytes and do not develop immunodeficiency. We have examined 10 chronically infected HIV-1—positive chimpanzees for evidence of progressive infection. In addition to 1 animal that developed AID...

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object a...

To determine whether ovariectomy exacerbates age-related cognitive decline, the performance of 6 aged monkeys that had been ovariectomized early in life (OVX-Aged) was compared to that of 8 age-matched controls with intact ovaries (INT-Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of visual recognition memory, object a...

Assessment of recognition memory was performed in a group of 12 rhesus monkeys, 19-24 years old (an age estimated to be comparable with early senescence in humans - i.e., 60s to early 70s). Their performance was compared with that of 14 young adult animals (5-14 years old, comparable to humans from the late teens to early 40s) on two tasks of recog...

To determine whether endogenous DHEAS level is related to cognitive performance in the rhesus monkey, we tested 9 young and 14 old monkeys on the acquisition and the 120 s delay condition of the delayed non-matching to sample and on the spatial delayed recognition span test. A single summary measure of cognitive ability, the cognitive performance i...

Twelve young (4-7 years of age) and 14 old (20-27 years of age) male and female rhesus monkeys were tested on seven cognitive tasks. Males and females performed similarly on tasks of object memory and executive function, but young males outperformed young females on a spatial memory task (Delayed Recognition Span Test) that requires the identificat...

Studies on human postmortem material report lower brain weights in older than in younger cohorts, whereas there is no apparent change with age in the rhesus monkey. In view of these contrasting results, we examined the pattern of brain weight across the life span in the chimpanzee, one of the closest biological relatives of humans. To place the stu...

Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibod...

It is only in the last 25 years that significant strides have been taken toward the development of primate models of normal human aging. Together with advances in the fields of molecular biology, neuroimaging, and behavioral neuroscience, these models have emerged as potentially important components in our understanding of the age-related cognitive...

This study investigated the effects of different rearing conditions on neural and cognitive development of male rhesus monkeys (Macaca mulatta). Infants raised individually in a nursery from 2 to 12 months of age (NURSERY, n=9) were compared to age-matched infants raised in a semi-naturalistic, social environment (CONTROL, n=11). Various brain regi...

This study investigated the effects of different rearing conditions on neural and cognitive development of male rhesus monkeys (Macaca mulatta). Infants raised individually in a nursery from 2 to 12 months of age (NURSERY, n=9) were compared to age-matched infants raised in a semi-naturalistic, social environment (CONTROL, n=11). Various brain regi...

Brain metabolites were measured by proton magnetic resonance spectroscopy in five young (4-10 years of age) and six old (24-30 years of age) adult rhesus monkeys. The two age groups had similar levels of N-acetylaspartate and of choline relative to creatine, but the ratio of myo-inositol/creatine was higher in each old monkey than in any of the you...

Cross-sectional studies on adult human autopsy material have shown that younger cohorts have heavier brains than older groups. We sought to determine whether a similar pattern is present in the rhesus monkey, a species that serves as a useful model of human brain and cognitive aging. Data were obtained from necropsies of 399 rhesus monkeys (180 fem...

It is only in the last 25 yr that significant strides have been taken toward the development of primate models of normal human aging. Together with advances in the fields of molecular biology, neuroimaging, and behavioral neuroscience, these models have emerged as potentially important components in our understanding of the age-related cognitive de...

To evaluate the association between selected chronic medical conditions (CMCs) and fall injury events at home among community-dwelling older persons. Population-based case-control study. The general community. Persons aged 65 and older living at home, excluding those using a wheelchair; 467 cases and 691 control subjects were studied. The main inde...

Assessment of recognition memory was performed on eight rhesus monkeys of advanced age (25 to 27 years of age) using the delayed recognition span test (DRST). Their performance was compared to that of five young adult animals (5 to 7 years of age) on two stimulus conditions of the DRST: spatial position and color. Both trial unique and repeating se...

Some studies report seasonal patterns of testicular function in male rhesus monkeys even when they are housed away from females, while others suggest that exposure to sexually active females is essential for male seasonality. We conducted the present experiment (1) to test claims that seasonal testicular activation occurs in the absence of females...

In order to determine whether there are age-related changes in the supragranular layer of the dentate gyrus of the rhesus monkey, we examined this layer in monkeys 4-35 years of age, spanning the entire range of adulthood of this species. Electron microscopic analyses were conducted to determine whether there is an age-related change in the number...

As part of the effort to characterize age-related cognitive changes in executive system function in a nonhuman primate model of human aging, the performance of seven rhesus monkeys, 20 to 28 years of age, was compared to that of five young adult monkeys, 6 to 11 years of age, on spatial and object reversal tasks. No differences in performance were...