Telomere microglia

Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0...

Microglia are a proliferative population of resident brain macrophages that under physiological conditions self-renew independent of hematopoiesis. Microglia are innate immune cells actively surveying the brain and are the earliest responders to injury. During aging, microglia elicit an enhanced innate immune response also referred to as 'priming'. To date, it remains unknown whether telomere shortening affects the proliferative capacity and induces priming of microglia. We addressed this issue using early (first-generation G1 mTerc(-/-) )- and late-generation (third-generation G3 and G4 mTerc(-/-) ) telomerase-deficient mice, which carry a homozygous deletion for the telomerase RNA component gene (mTerc)...

The susceptibility of the aging brain to neurodegenerative disease may in part be attributed to cellular aging of the microglial cells that survey it. We investigated the effect of cellular aging induced by telomere shortening on microglia by the use of mice lacking the telomerase RNA component (TERC) and design-based stereology. TERC knockout (KO) mice had a significantly reduced number of CD11b(+) microglia in the dentate gyrus. Because of an even greater reduction in dentate gyrus volume, microglial density was, however, increased...

The telomerase reverse transcriptase protein TERT has recently been demonstrated to have a variety of functions both in vitro and in vivo, which are distinct from its canonical role in telomere extension. In different cellular systems, TERT protein has been shown to be protective through its interaction with mitochondria. TERT has previously been found in rodent neurons, and we hypothesize that it might have a protective function in adult human brain. Here, we investigated the expression of TERT at different stages of Alzheimer's disease pathology (Braak Stages I-VI) in situ and the ability of TERT to protect against oxidative damage in an in vitro model of tau pathology...

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. In AD, monocytes migrate across the blood-brain barrier and differentiate into microglia, are linked to inflammatory responses and display age-dependent decreases in telomere lengths. METHODS: Six monocyte-specific chemokines and the (telomere-associated) tumor suppressor proteins p53 and p21 were determined by multiplex immunoassay in plasma and monocyte extracts of patients with AD or mild cognitive impairment, and levels were compared between patients and controls (without cognitive impairment)...

Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells. Studies on telomere lengths in patients with Alzheimer's disease have revealed contrary results and the functional role of telomere shortening on brain ageing and Alzheimer's disease is not known. Here, we have investigated the effects of telomere shortening on adult neurogenesis and Alzheimer's disease progression in mice...

Despite the fact that Alzheimer's disease was identified more than 100 years ago, its cause remains elusive. Although the chance of developing Alzheimer's disease increases with age, it is not a natural consequence of aging. This article proposes that dental X-rays can damage microglia telomeres - the structures at the end of chromosomes that determine how many times cells divide before they die - causing them to age prematurely. Degenerated microglia lose their neuroprotective properties, resulting in the formation of neurofibrillary tau tangles and consequently, the neuronal death that causes Alzheimer's dementia...

Until now, interest in dental pulp stem/stromal cell (DPSC) research has centered on mineralization and tooth repair. Beginning a new paradigm in DPSC research, we grafted undifferentiated, untreated DPSCs into the hippocampus of immune-suppressed mice. The rhesus DPSC (rDPSC) line used was established from the dental pulp of rhesus macaques and found to be similar to human bone marrow/mesenchymal stem cells, which express Nanog, Rex-1, Oct-4, and various cell surface antigens, and have multipotent differentiation capability...

Amyotrophic Lateral Sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy. In this study MSCs were isolated from bone marrow of 9 patients with definite ALS. Growth kinetics, immunophenotype, telomere length and karyotype were evaluated during in vitro expansion...

Advanced age and presence of intracerebral amyloid deposits are known to be major risk factors for development of neurodegeneration in Alzheimer's disease (AD), and both have been associated with microglial activation. However, the specific role of activated microglia in AD pathogenesis remains unresolved. Here we report that microglial cells exhibit significant telomere shortening and reduction of telomerase activity with normal aging in rats, and that in humans there is a tendency toward telomere shortening with presence of dementia...

Microglial cells undergo cell division in vitro, as well as in vivo after brain injury. Mitotic activity of microglia suggests that they have limited life spans and rely on self-renewal to replace senescent cells. In the current study we examined long-term effects of antioxidants vitamin E and alpha-lipoic acid on cultured rat microglia with respect to proliferative ability, telomere length, telomerase activity, and interleukin-1beta (IL-1beta) production. We report that vitamin E induces dramatic microglial proliferation, as measured by MTT assay and BrdU incorporation, surpassing that of the well-known microglial mitogen granulocyte macrophage-colony stimulating factor, and therefore establishing vitamin E as the most potent, known mitogen for microglia in vitro...

The adult central nervous system (CNS) is generally thought of as a postmitotic organ. However, DNA labeling studies have shown that one major population of nonneuronal cells, called microglia, retain significant mitotic potential. Microglial cell division is prominent during acute CNS injury involving neuronal damage or death. Prior work from this laboratory has shown that purified microglia maintained in vitro with continual mitogenic stimulation exhibit telomere shortening before entering senescence. In the current study, we sought to investigate whether telomere shortening occurs in dividing microglia in vivo...

With each cell division, telomeres progressively shorten until they reach a critical length, at which point the cells enter cellular senescence. Microglia, a non-neuronal cell type residing within the central nervous system (CNS), play vital roles in maintaining neuronal function, health, and survival in both the normal and pathological CNS. A recent article described an increased incidence of microglial cytoplasmic structural abnormalities (i.e., swelling, twisted and shortened processes, and fragmentation) and dystrophy occurring in the cerebral cortex of human brains with age...

Normal somatic cells have a finite replicative capacity. With each cell division, telomeres, the ends of linear chromosomes, progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell type in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. Previous research in our laboratory has found that telomeres shorten in rat microglia with increasing time in vitro...

Normal somatic cells have a finite replicative capacity. With each cell division, telomeres shorten progressively until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell types in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. In this study, we show that telomere shortening accompanied by low to moderate telomerase activity, and ultimately senescence, occurs in rat microglia in vitro...

Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG-EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra-RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non-MHC genome...