Your search for: 'author:("Kesavalu, Lakshmyya")' has returned 5 results. (0.015s) Save search

Authors: Singhrao, Sim K. | Harding, Alice | Chukkapalli, Sasanka | Olsen, Ingar | Kesavalu, Lakshmyya | Crean, StJohn

Article Type: Review Article

Abstract: The primary goal of advancement in clinical services is to provide a health care system that enhances an individual’s quality of life. Incidence of diabetes mellitus, cardiovascular disease, and associated dementia coupled with the advancing age of the population, have led to an increase in the worldwide challenge to the healthcare system. In order to overcome these challenges, prior knowledge of common, reliable risk factors and their effectors is essential. Oral health constitutes one such relatively unexplored but indispensable risk factor for aforementioned co-morbidities, in the form of poor oral hygiene and tooth loss during aging. Behavioral traits such as …low education, smoking, poor diet, neglect of oral health, lack of exercise, and hypertension are few of the risk factors that are shared commonly among these conditions. In addition, common genetic susceptibility traits such as the apolipoprotein E gene, together with an individual’s lifestyle can also influence the development of co-morbidities such as periodontitis, atherosclerosis/stroke, diabetes, and Alzheimer’s disease. This review specifically addresses the susceptibility of apolipoprotein E gene allele 4 as the plausible commonality for the etiology of co-morbidities that eventually result from periodontal diseases and ultimately progress to dementia. Show more

Keywords: Alzheimer’s disease, apolipoprotein, atherosclerosis, co-morbidities, dyslipidemia, periodontitis

DOI: 10.3233/JAD150690

Citation: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 935-948, 2016

Authors: Poole, Sophie | Singhrao, Sim K. | Kesavalu, Lakshmyya | Curtis, Michael A. | Crean, StJohn

Article Type: Research Article

Abstract: The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains …were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology. Show more

Keywords: Alzheimer's disease, lipopolysaccharide, periodontal disease, Porphyromonas gingivalis, postmortem

DOI: 10.3233/JAD-121918

Citation: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 665-677, 2013

Authors: Singhrao, Sim K. | Harding, Alice | Simmons, Tal | Robinson, Sarita | Kesavalu, Lakshmyya | Crean, StJohn

Article Type: Review Article

Abstract: Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting tissues with bacterial etiology affecting all age groups, becoming chronic in a subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are implicated in the development of a number of inflammatory pathologies at remote organ sites, including Alzheimer's disease (AD). The initial inflammatory hypothesis proposed that AD hallmark proteins were the main contributors of central nervous system (CNS) inflammation. This hypothesis is expanding to include the role of infections, lifestyle, and genetic and environmental factors in the pathogenesis of AD. Periodontal disease (PD) typifies a condition that …encompasses all of the above factors including pathogenic bacteria. These bacteria not only are the source of low-grade, chronic infection and inflammation that follow daily episodes of bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing food, and during dental procedures, but they also disseminate into the brain from closely related anatomical pathways. The long-term effect of inflammatory mediators, pathogens, and/or their virulence factors, reaching the brain systemically or otherwise would, over time, prime the brain's own microglia in individuals who have inherent susceptibility traits. Such susceptibilities contribute to inadequate neutralization of invading agents, upon reaching the brain. This has the capacity to create a vicious cycle of sustained local inflammatory milieu resulting in the loss of cytoarchitectural integrity and vital neurons with subsequent loss of function (deterioration in memory). The possible pathways between PD and AD development are considered here, as well as environmental factors that may modulate/exacerbate AD symptoms. Show more

Keywords: Alzheimer's disease, inflammation, oral health, periodontal disease

DOI: 10.3233/JAD-140387

Citation: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 723-737, 2014

Authors: Poole, Sophie | Singhrao, Sim K. | Chukkapalli, Sasanka | Rivera, Mercedes | Velsko, Irina | Kesavalu, Lakshmyya | Crean, StJohn

Article Type: Research Article

Abstract: Periodontal disease is a polymicrobial inflammatory disease that leads to chronic systemic inflammation and direct infiltration of bacteria/bacterial components, which may contribute to the development of Alzheimer's disease. ApoE-/- mice were orally infected (n = 12) with Porphyromonas gingivalis , Treponema denticola , Tannerella forsythia , and Fusobacterium nucleatum as mono- and polymicrobial infections. ApoE-/- mice were sacrificed following 12 and 24 weeks of chronic infection. Bacterial genomic DNA was isolated from all brain tissues except for the F. nucleatum mono-infected group. Polymerase chain reaction was performed using universal 16 s rDNA primers and species-specific primer sets for each organism …to determine whether the infecting pathogens accessed the brain. Sequencing amplification products confirmed the invasion of bacteria into the brain during infection. The innate immune responses were detected using antibodies against complement activation products of C3 convertase stage and the membrane attack complex. Molecular methods demonstrated that 6 out of 12 ApoE-/- mice brains contained P. gingivalis genomic DNA at 12 weeks (p = 0.006), and 9 out of 12 at 24 weeks of infection (p = 0.0001). Microglia in both infected and control groups demonstrated strong intracellular labeling with C3 and C9, due to on-going biosynthesis. The pyramidal neurons of the hippocampus in 4 out of 12 infected mice brains demonstrated characteristic opsonization with C3 activation fragments (p = 0.032). These results show that the oral pathogen P. gingivalis was able to access the ApoE-/- mice brain and thereby contributed to complement activation with bystander neuronal injury. Show more

Keywords: Alzheimer's disease, chronic periodontitis, inflammation, periodontal bacteria

DOI: 10.3233/JAD-140315

Citation: Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 67-80, 2015

Authors: Rokad, Farheen | Moseley, Ryan | Hardy, Rowan S. | Chukkapalli, Sasanka | Crean, StJohn | Kesavalu, Lakshmyya | Singhrao, Sim K.

Article Type: Research Article

Abstract: The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain. This study examined oxidative stress, in the form of increased protein carbonylation and oxidative protein damage, in the tumor necrosis factor-α (TNF-α) transgenic mouse that models inflammatory TNF-α excess during bacterial infection; and in the apolipoprotein knockout (ApoE– / – ) mouse brains, following Porphyromonas gingivalis gingival monoinfection. Following 2,4-dinitrophenylhydrazine derivatization, carbonyl groups were detected in frontal lobe brain tissue lysates by immunoblotting and immunohistochemical analysis of fixed tissue sections from the frontotemporal lobe and the hippocampus. …Immunoblot analysis confirmed the presence of variable carbonyl content and oxidative protein damage in all lysates, with TNF-α transgenic blots exhibiting increased protein carbonyl content, with consistently prominent bands at 25 kDa (p  = 0.0001), 43 kDa, and 68 kDa, over wild-type mice. Compared to sham-infected ApoE–/– mouse blots, P. gingivalis -infected brain tissue blots demonstrated the greatest detectable protein carbonyl content overall, with numerous prominent bands at 25 kDa (p  = 0.001) and 43 kDa (p  = 0.0001) and an exclusive band to this group between 30–43 kDa* (p  = 0.0001). In addition, marked immunostaining was detected exclusively in the microvasculature in P. gingivalis -infected hippocampal tissue sections, compared to sham-infected, wild-type, and TNF-α transgenic mice. This study revealed that the hippocampal microvascular structure of P. gingivalis -infected ApoE– / – mice possesses elevated oxidative stress levels, resulting in the associated tight junction proteins being susceptible to increased oxidative/proteolytic degradation, leading to a loss of functional integrity. Show more

Keywords: Hippocampus, infection, microvasculature, oxidative stress/damage, Porphyromonas gingivalis, tight junction proteins

DOI: 10.3233/JAD-170304

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 359-369, 2017