Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara; Rosene, Douglas L.

doi:10.3389/fnsys.2015.00102

Cited by 72 publications

(64 citation statements)

References 99 publications

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“…The age‐related decrease of neurogenesis is well described in the DG of experimental animals from rodents to primates (Kuhn et al, ; Leuner, Kozorovitskiy, Gross, & Gould, ; Ngwenya, Heyworth, Shwe, Moore, & Rosene, ; Walter et al, ). The depletion of NSCs population might be the main force driving the decrease of neurogenesis with age (Encinas et al, ; Walter et al, ).…”

Section: Discussionmentioning

confidence: 98%

Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

et al. 2019

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Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving the age‐dependent decline of hippocampal neurogenesis are yet not fully understood. The progressive loss of neural stem cells (NSCs) is a main factor, but the true neurogenic output depends initially on the actual number of activated NSCs in each given time point. Because the fraction of activated NSCs remains constant relative to the total population, the real number of activated NSCs declines in parallel to the total NSC pool. We investigated aging‐associated changes in NSCs and found that there are at least two distinct populations of NSCs. An alpha type, which maintains the classic type‐1 radial morphology and accounts for most of the overall NSC mitotic activity; and an omega type characterized by increased reactive‐like morphological complexity and much lower probability of division even under a pro‐activation challenge. Finally, our results suggest that alpha‐type NSCs are able to transform into omega‐type cells overtime and that this phenotypic and functional change might be facilitated by the chronic inflammation associated with aging.

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Section: Discussionmentioning

confidence: 98%

Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

et al. 2019

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“…In terms of ageing this includes greying and thinning of hair, redistribution of body fat, loss of skin tone, loss of vigour and loss of muscle tone4567. With age there are increases in clinical manifestations of diseases and disorders that also increase in prevalence with advancing age in humans, including diabetes, neoplasia, sarcopenia, bone loss, altered immune function and cognitive decline348. Like humans, nonhuman primates are genetically heterogeneous so that phenotypes of ageing are non-uniformly manifested among individual animals.…”

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confidence: 99%

Caloric restriction improves health and survival of rhesus monkeys

et al. 2017

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Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

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“…Every 10 th section of the granule cell layer (GCL) that includes the subgranular zone on one half of each brain were counted. An estimate of the total number of cells was calculated by multiplying the aggregate by 20 (Ngwenya et al, 2015;Snyder et al, 2005;.…”

Section: 1 Brdu and Ki67mentioning

confidence: 99%

Sex Differences in Maturation and Attrition of Adult Neurogenesis in the Hippocampus

Yagi

Splinter

Tai

et al. 2019

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Sex differences exist in the regulation of adult neurogenesis in the hippocampus in response to hormones and cognitive training. Here we investigated the trajectory and maturation rate of adult-born neurons in the dentate gyrus (DG) of male and female rats. Sprague-Dawley rats were perfused one, two or three weeks after BrdU injection, marking newly dividing cells.Adult-born neurons (BrdU/NeuN-ir) matured faster in males compared to females. Males had a greater density of neural stem cells (Sox2-ir) in the dorsal, but not in the ventral, DG and had higher levels of cell proliferation (Ki67-ir) than females. Males had a greater reduction in neurogenesis between one and two weeks after mitosis, while females showed similar levels of neurogenesis throughout. The faster maturation and attrition of new neurons suggests greater potential for neurogenesis to respond to external stimuli in males compared to females and emphasizes the importance of studying sex on adult hippocampal neurogenesis.(Fisher Scientific) solution for cryoprotection and remained in the solution until sectioning. Brains were sliced into 30 μ m coronal sections using a Leica SM2000R microtome (Richmond Hill, Ontario, Canada). Sections were collected in series of ten throughout the entire rostral-caudal extent of the hippocampus and stored in anti-freeze solution consisting of ethylene glycol, glycerol and 0.1M PBS at -20°C until immunostaining. Complete series of sections were immunohistochemically stained for BrdU/DCX and BrdU/NeuN to examine sex differences in the maturation timeline of new neurons, for Sox2 to examine the number of neural stem cells, and for Ki67 to examine actively dividing progenitor cells. In addition, the brain sections were double-stained for BrdU/Sox2 to examine changes of Sox2 expression over the three weeks after BrdU injection. Radioimmunoassay for 17β-estradiol and testosteronePrevious studies reported that 17β-estradiol increases cell proliferation in females but not males (Tanapat et al., 1999;Barker and Galea, 2008) and androgens can influence survival of new neurons in males but not females (Spritzer and Galea, 2007;Duarte-Guterman et al., 2019).Thus, we examined serum levels of 17β-estradiol and testosterone in females and males, respectively.Blood samples were stored at 4℃ overnight and centrifuged at 10g for 15 minutes to collect serum.Serum 17β-estradiol levels in female rats and serum testosterone levels in male rats were assayed using commercially available radioimmunoassay (RIA) kits from Beckman Coulter (Brea, USA) or MP Biomedicals (Santa Ana, USA) respectively. The sensitivity of the RIA kits was 0.75 ng/mL for 17β-estradiol and 0.03ng/mL for testosterone. The intra-and inter-assay coefficient of variation were <8.9% and <12.2% respectively for 17β-estradiol and <8.2% and <13.2% for testosterone.None of the females were in proestrus at the time of sacrifice. 4. Immunohistochemistry 4. 1. BrdU/NeuN, BrdU/DCX or BrdU/Sox2 double-stainingThe exogenous DNA synthesis marker, 5-bromo-2'-deoxyuridine (BrdU) is i...

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Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

Cited by 72 publications

References 99 publications

Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

Caloric restriction improves health and survival of rhesus monkeys

Sex Differences in Maturation and Attrition of Adult Neurogenesis in the Hippocampus

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