Several functions have been attributed to the cellular prion protein, PrPc, amongst which its anti-oxidant role has rapidly been gaining interest in the recent years. We and others have previously shown, that PrPc expressing cells, of neuroblastoma or epithelial origin, seem to exhibit a higher overall viability towards paraquat toxicity than cells expressing basal or low levels of the protein. Although several studies propose a protective mechanism that involves PrPc dependent activation of the superoxide dismutase (SOD) enzymatic machinery or an activation of its own intrinsic antioxidant function, others argue against this SOD-like role. Our objective was to investigate, at a biological and proteomic level, by which potential mechanism PrPc could protect neuroblastoma cells against paraquat induced oxidative damage. Using a biological aproach, we firstly evaluated the status of the Cu/Zn-SOD enzyme in Human neuroblastoma cells expressing different forms of PrPc following their exposure to paraquat. Next, we performed a proteomic study to investigate by which other potential mechanism(s), PrPc could protect the cell against paraquat induced oxidative stress. Our proteomic approach made use of an optimised two-dimensional liquid chromatography system, the ProteomeLab PF-2D, and reverse phase chromatography coupled with lava purple stained SDS-PAGE, both interfaced with tandem mass spectrometry. An interesting aspect of our study has been the development of an original immunoproteomic technique called immuno-PF2D-MS/MS, coupling classical immunological methods to a two-dimensional liquid chromatography proteomic tool interfaced with tandem mass spectrometry. We have proposed this technique for antigenic and serological characterization that have important implications in the study of biomarkers. Another important aspect of our study has been the detection of several candidates that could participate in PrPc-mediated protection against paraquat induced oxidative stress. Although, it was out of our scope to investigate each of these candidates in the present study, it presents an interesting perspective for future studies. We have, however, shown the implication of one such candidate: PARP-1. Complimentary tests will be necessary in the future to confirm the actual interaction of this candidate with PrPc.

Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases that are characterised by long incubation periods, protein aggregation and vacuolation. During TSE pathogenesis the normal, cellular prion protein, (PrPC), which is encoded by the gene PRNP, misfolds and accumulates as abnormal disease associated prion protein, (PrPSc) within the central nervous system. Variants of the Prion protein gene are associated with susceptibility to TSE disease. For example sheep scrapie disease is modulated by several PRNP alleles, with certain alleles carried by susceptible animals being different from those carried by resistant animals. The mechanisms linking PRNP genetics and disease is poorly understood but may involve protein sequence, PrPC expression levels, and possibly differences in protein processing. Post-translational modification of PrPC leads to specific cleavage (alpha cleavage) between amino acids 115/116 of ovine PrP, producing two fragments C1 and N1. Cleavage of PrP may occur as a protective mechanism, as a response to changes in the cellular environment or as a feature of an as yet unknown biological function. In the context of TSEs, alpha cleavage may inadvertently provide a protective role by reducing available PrPC protein for conversion into PrPSc, assuming that the C1 fragment would be an inefficient substrate for conversion, the opposite theory was also proposed. The former hypothesis became the focus of this present study, with the idea that total full-length PrPC, total C1 or the ratio between full-length PrPC and C1 may be linked to differences in scrapie susceptibility. To investigate these aims the C1 fragment was measured as a percentage of total PrPC in different PRNP genotypes with varying degrees of susceptibility to scrapie and in different brain regions. This study found that PrPC alpha cleavage increased during development from the new born lamb to the adult sheep, which may have consequences for the susceptibility differences related to age. There are also variations in the amount of alpha cleavage between brain regions such as cortex and medulla that may influence scrapie strain targeting. Overall the amount of the C1 fragment in the different brain areas varied as much as 10x (range 5% to 60%). There was a significant difference in the ratio of C1 to the other PrPC forms between two PRNP genotype groups carrying the VRQ and ARQ allele but there was no correlation between C1 level and scrapie susceptibility or scrapie incubation period in our scrapie models. Alpha cleavage of PrPC also occurs in various transgenic mouse models expressing different ruminant PrP sequences. In PrPC over-expressing transgenic mouse models a higher ratio of C1 was observed, this may suggest a link between PrPC expression levels and alpha cleavage. Transgenic mice are therefore important models to further investigate the link between PrPC biology and scrapie disease phenotype. In conclusion, this thesis has shown for the first time that certain ovine PRNP alleles can influence alpha cleavage of the PrPC protein; however it appears not to be a significant indicator of TSE disease susceptibility in sheep.

Transmissible spongiform encephalopathies (TSEs), such as scrapie and variant Creutzfeldt-Jakob disease are infectious, fatal, neurodegenerative diseases. Following peripheral infection TSE agents usually accumulate in lymhoid tissues before spreading to the central nervous system. In mice, follicular dendritic cells (FDCs) expressing the host prion protein (PrPC) are essential for scrapie agent accumulation in lymphoid tissues. The accumulation of the scrapie agent on FDCs is critical for the efficient spread of infection to the brain. However, it is unknown whether FDCs themselves actively replicate the scrapie agent, or simply accumulate it following production by other cells types such as neurones, lymphocytes or other stromal cell populations. To definitively address this issue a transgenic mouse model was created in which PrPC is switched on or off exclusively on FDCs. Expression of cre-recombinase (Cre) under the action of cell-specific gene promoters can be used to induce or delete the expression of a target gene in specific cell populations. In this model, Cre expression is driven by the complement receptor type 2 gene (Cr2/CD21) which is expressed by FDCs and mature B lymphocytes. Characterisation of the CD21-cre mouse line was achieved by crossing with a ROSA26 reporter strain. The CD21-cre mouse line was subsequently crossed with floxed-PrP mouse lines to produce compound transgenic mouse lines in which PrPC expression was switched on or off, only in FDCs. Cre expression by B lymphocytes was eliminated by γ-irradiation and grafting recipient mice with Cre-deficient bone marrow. Immunohistochemical analysis confirmed the expression PrPC had been switched on or off exclusively on FDCs. Subsequently, the mice were challenged with scrapie by intra-peritoneal injection to determine the precise role of FDCs in the accumulation of scrapie in lymphoid tissues. Switching off PrPC expression exclusively on FDCs prevented the accumulation of TSE agent specific disease-associated PrPSc in the spleen after i.p inoculation. Conversely, in mice in which PrPC was expressed only on FDC, successful replication of the agent occurred on the FDC network in the spleen. Taken together, these data show PrPC-expressing FDCs alone are sufficient to support the accumulation of the scrapie agent within lymphoid tissues. Furthermore, these data suggest FDC replicate the TSE agent and do not simply accumulate it following synthesis by other cell types.

Transmissible spongiform encephalopathies (TSEs) are a group of fatal, neurodegenerative diseases that can affect both humans and animals. TSEs can be sporadic, familial, or acquired diseases. The prion hypothesis states that a misfolded form of the host glycoprotein, PrPC, acts as the infectious agent in TSE disease. The misfolded form, PrPSc, is increased in β-sheet content, detergent insoluble and partially resistant to proteinase K (PK) digestion. Based on the prion hypothesis, most current post-mortem diagnostic tests rely on the presence of PrPSc as indicative of TSE disease. However, recently experimental cases of TSE disease have been identified where no PrPSc deposition is evident. One example of this is a murine transgenic model of Gerstmann Sträussler Scheinker (GSS) disease. GSS is a familial TSE disease, caused by a number of different mutations in human PrP including a point mutation from proline to leucine at residue 102. A murine model of GSS disease, produced through gene-targeting, contains the same point mutation at the equivalent residue, 101, in murine PrP. These mice do not develop spontaneous disease during their lifespan, but when inoculated intra-cerebrally with either human P102L GSS (101LL/GSS) or hamster 263K scrapie (101LL/263K); develop a clinical disease and vacuolar TSE-related pathology. Upon biochemical and immunohistochemical analysis, the brain tissues of these clinically ill mice contain little or no detectable PrPSc. However titration experiments have previously shown infectivity titres of 107-109IU/g of brain tissue. Standard PK digestion (at 37°C), NaPTA precipitation and isolation of PrPSc through detergent insolubility and differential centrifugation all confirmed the observation of little or no detectable PK-resistant PrP (PrP-res) in the 101LL/GSS and 101LL/263K brain tissues, despite the high levels of TSE infectivity. The presence of PrPSc and/or TSE infectivity in the spleen during disease pathogenesis is dependent upon TSE agent strain and host species. Previous studies utilising wild-type mice infected with ME7, have shown that the levels of infectivity observed in spleen tissue are 2- 3log10 lower than those observed in the brain tissue of the same mice. However, experiments conducted as part of this thesis showed that sub-passage of both the brain and spleen tissue from clinically ill 101LL/GSS and 101LL/263K mice into 101LL mice by intra-cerebral inoculation result in short incubation periods, indicating that infectivity levels were similarly high in both tissues. Biochemical analysis of the primary spleen tissue identified the presence of PrP-res, albeit at lower levels than those observed in wild-type spleens infected with a standard laboratory TSE strain, ME7 or 79A. However, the presence of PrP-res indicates that the spleen has a role in disease pathogenesis, which will require further investigation. Additionally, the spleen tissue maintains the discrepancy between PrP-res and TSE infectivity that is observed in the brain tissue of these models and further questions the prion hypothesis. As little or no PrP-res was detectable in the brain tissues of 101LL/GSS and 101LL/263K mice by standard biochemical and immunohistochemical techniques, it was hypothesised that an in vitro amplification technique, protein misfolding cyclic amplification (PMCA) could amplify PrPSc to detectable levels. A series of optimisation experiments were performed to produce a reliable positive control for amplification of mouse PrPSc from a standard laboratory mouse TSE strain, 79A or ME7, with a normal wild-type mouse brain homogenate substrate. While a wide range of technical and experimental conditions were investigated, consistent and reproducible amplification of mouse PrPSc was not achieved and therefore amplification of PrPSc from 101LL/GSS and 101LL/263K tissues could not be performed as interpretation of results would be complicated without the presence of a positive control. Previous research has shown that while other commercial assays, e.g. TeSeE (BioRad), identified tissues from these models as borderline positive or negative for TSE disease, one TSE diagnostic assay, the IDEXX HerdChek kit, that utilises the Seprion ligand, identified both the brain and spleen tissue from 101LL/GSS and 101LL/263K clinical mice as positive for TSE disease. In order to identify if TSE infectivity is associated with the target of the Seprion ligand, brain tissue homogenates from 101LL/GSS, 101LL/263K and a positive control wild-type/79A homogenate were depleted of the Seprion ligand target utilising a PAD-beads kit (Microsens Biotechnologies), which incorporates the Seprion ligand as the capture agent, in combination with magnetic beads. Upon inoculation, a single depletion of the homogenates produced no significant reduction in incubation period to clinical disease in either the depleted homogenates or the wash buffers produced, in comparison to a non-depleted brain homogenate. This result indicates that a single depletion with the Seprion ligand, did not remove enough of the aggregated protein to significantly alter the level of infectivity in the depleted homogenate and that any infectious agent, which was initially bound to the Seprion ligand due to non-specific interactions, was then released during the wash steps of the procedure. Proteomic differences between all components produced during a single depletion of an infected brain homogenate, wild-type/79A, or a normal uninfected brain homogenate were assessed to potentially identify the target of the Seprion ligand. In conclusion, these murine models of TSE disease, 101LL/GSS and 101LL/263K, which contain both high infectivity levels with little or no PrP-res in the brain tissue and similar high levels of infectivity with low levels of PrP-res in the spleen, questions the accepted correlation between levels of infectivity and PrP-res or PrPSc as proposed by the prion hypothesis. It is hypothesised that either an alternative form of PrP, which has not yet been identified is the infectious agent in these disease models, or that the TSE infectious agent is a component which associates with PrPSc rather than being PrPSc itself. The eventual identification of the infectious agent present in these unusual disease models will increase our understanding of these diseases, potentially offer improved diagnostics for infectivity, and perhaps identify novel therapeutic targets.

The Transmissible Spongiform Encephalopathies (TSEs) or “prion” diseases are a group of fatal neurodegenerative diseases the aetiology of which is not fully understood. These diseases are characterised by a number of pathological changes in the central nervous system (CNS) including; vacuolation of the neuropil, gliosis and deposition of PrPSc; the abnormal form of the host glycoprotein PrP. Although the major pathology in these diseases is associated with the CNS the immune system is central to the pathogenesis of many natural and experimental TSEs including natural scrapie in sheep, chronic wasting disease in free ranging and captive deer and variant CJD (vCJD) in humans. Unlike many infectious diseases where deficiencies in immune function are opportunistic for the invading pathogen a competent immune system is required for efficient TSE infection via peripheral routes. As infection of the lymphoid tissues in many TSEs can occur many months before the detection of infectivity in the CNS, the determination of those cells in the lymphoid system has been the focus of much research and a number of studies now point towards the importance of the follicular dendritic cell (FDC), a long-lived radio resistant cell, in TSE pathogenesis. The involvement of FDCs in peripheral TSE pathogenesis relates to the inability of ionising radiation to influence pathogenesis, the association of PrP protein with FDCs in both uninfected and infected lymphoid tissues, and the demonstration that TSE pathogenesis is severely impaired in mice devoid of these cells. The aims of this thesis were to further understand the role of FDCs in the pathogenesis of a range of mouse-adapted experimental TSE strains and to determine if peripherally acquired TSE infections are influenced by host age or by stimulation of the immune system. Using chimaeric mouse models where a mismatch in the expression of PrP protein between FDCs and lymphoid/myeloid cells was produced, further evidence for a critical role for in the pathogenesis of the ME7 TSE strain was produced. Although these findings produced strong evidence that FDCs were important for the ME7 strain the possibility that different TSE strains may target different cell types in the peripheral lymphoid system was explored using a range of mice with specific immunological defects. Infection of these mice with several experimental TSE strains showed that the presence of mature FDCs was also important for the pathogenesis of the strains tested. Clinical cases of vCJD have been confined almost exclusively to young adults, although the reasons behind this apparent age-related susceptibility are not fully understood. The capacity of the immune system to mediate immune responses to pathogens declines with age as a result of impaired lymphocyte and FDC function. As FDCs are critically involved in the pathogenesis of many TSEs, including vCJD, it was hypothesised that an aging immune system may impair disease pathogenesis. Peripheral infection of senescent mice failed to produce clinical disease during lifespan, although evidence of disease transmission, was detected in a proportion of aged mice. These findings demonstrate that this inefficient disease transmission, as a consequence of age, may lead to considerable levels of sub-clinical disease within the population. Finally the influence of immune system stimulation, by the generation of a humoral immune response, on peripheral TSE pathogenesis was investigated. These findings demonstrated that immunisation can influence pathogenesis, but only during the early stages of infection prior to spread to the CNS. These data imply that modulation of the immune system does not alter TSE pathogenesis once disease has been initiated in the CNS. Finally, these studies have found some preliminary evidence that TSE infection may induce FDC activation suggesting that TSE infection may influence the immune response. Together, these data show that a functional immune system and specifically, the presence of mature FDCs, are central to the pathogenesis of peripherally acquired TSE infections.

Transmissible spongiform encephalopathies (TSEs) or prion diseases, are subacute neurodegenerative diseases that infect humans and animals. Many of these diseases are acquired by peripheral exposure (e.g. orally). After oral exposure prion replication within the Peyer's patches (PP) in the small intestine is necessary for the efficient spread of the disease to the brain. Within the intestine, bacteria and pathogenic microorganisms can affect the status of the gut associated lymphoid tissue (GALT). GALT consists of PP and isolated lymphoid follicles (ILF) that maintain homeostasis and protect from infections. Therefore, factors which modify GALT status, might dramatically affect oral prion disease pathogenesis by influencing the uptake of prions from the gut lumen or expanding their distribution within the host. Chronic intestinal helminth infections are common in animals and in man, and can cause significant pathology within the intestine. Little is known of the effects that intestinal helminth infections may have on oral prion diseases susceptibility. Therefore, in this study the influence that co-infection with Heligmosomoides polygyrus (a natural pathogen of the mouse small intestine) may have on oral prion disease pathogenesis and susceptibility was determined. The studies consisted of groups of 4 (for H. polygyrus characterization and for early prion detection) and 8 (for H. polygyrus-prion co-infection to terminal stage) mice infected with H. polygyrus (orally) alone or subsequently infected with ME7 scrapie prions (orally) at different time-points after parasitic infection. The effects of the H. polygyrus infection alone, and on oral prion disease pathogenesis and susceptibility were then determined. Initially the characterization of H. polygyrus infection on the host intestine revealed that this parasite caused significant pathology in the small intestine and affected the GALT microarchitecture. In the PP follicles, H. polygyrus infection increased the area of follicular dendritic cell expression, altered the positioning of mononuclear phagocytes and increased M cell density. H. polygyrus infection also reduced the number of ILF in both the small and large intestines. Additional studies in mice co-infected with a low dose of prions, revealed that these pathological changes affected the survival time and disease susceptibility. Data also show that the extent of the effects on prion disease pathogenesis and susceptibility were dependent on the stage of the helminth infection at which the mice were orally-exposed to prions. Data demonstrate that co-infection with the gastrointestinal helminth H. polygyrus can influence oral prion disease pathogenesis and susceptibility. Helminth infections can significantly modify the microarchitecture of the gut and the GALT. Data presented suggest the pathological changes that pathogens such as small intestinal helminths cause, may also influence the uptake of prions from the gut lumen after oral exposure.

Cellular prion protein (PrPc) is a GPI–anchored protein, of unknown function, found in a number of cells throughout the body. It is now widely believed that a mis-folded, protease resistant form of this protein is responsible for a group of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSE), including Creutzfeldt-Jakob disease (CJD) and kuru in humans, scrapie in sheep, chronic wasting disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE) in cattle. Although the exact function of PrPc is unknown it has been implicated in copper binding, signal transduction and cell adhesion. The pathogenesis of prion diseases is poorly understood, however it is known that PrPc must be present in order for the disease to progress. Platelets have been shown to be the largest reservoir of PrPc in peripheral blood cells and previous studies in animal models have suggested platelets may also be involved in TSE infectivity. In this study, we determine the exact location of PrPc within human platelets, examine the mobilization and release of PrPc from activated platelets on both microvesicles and exosomes and suggest a possible role for platelets in prion infectivity. In addition we examine the role of PrPc within normal platelet functions including aggregation, signal transduction and adhesion. / May 2005

Cellular prion protein (PrPc) is a GPI–anchored protein, of unknown function, found in a number of cells throughout the body. It is now widely believed that a mis-folded, protease resistant form of this protein is responsible for a group of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSE), including Creutzfeldt-Jakob disease (CJD) and kuru in humans, scrapie in sheep, chronic wasting disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE) in cattle. Although the exact function of PrPc is unknown it has been implicated in copper binding, signal transduction and cell adhesion. The pathogenesis of prion diseases is poorly understood, however it is known that PrPc must be present in order for the disease to progress. Platelets have been shown to be the largest reservoir of PrPc in peripheral blood cells and previous studies in animal models have suggested platelets may also be involved in TSE infectivity. In this study, we determine the exact location of PrPc within human platelets, examine the mobilization and release of PrPc from activated platelets on both microvesicles and exosomes and suggest a possible role for platelets in prion infectivity. In addition we examine the role of PrPc within normal platelet functions including aggregation, signal transduction and adhesion.

Cellular prion protein (PrPc) is a GPI–anchored protein, of unknown function, found in a number of cells throughout the body. It is now widely believed that a mis-folded, protease resistant form of this protein is responsible for a group of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSE), including Creutzfeldt-Jakob disease (CJD) and kuru in humans, scrapie in sheep, chronic wasting disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE) in cattle. Although the exact function of PrPc is unknown it has been implicated in copper binding, signal transduction and cell adhesion. The pathogenesis of prion diseases is poorly understood, however it is known that PrPc must be present in order for the disease to progress. Platelets have been shown to be the largest reservoir of PrPc in peripheral blood cells and previous studies in animal models have suggested platelets may also be involved in TSE infectivity. In this study, we determine the exact location of PrPc within human platelets, examine the mobilization and release of PrPc from activated platelets on both microvesicles and exosomes and suggest a possible role for platelets in prion infectivity. In addition we examine the role of PrPc within normal platelet functions including aggregation, signal transduction and adhesion.

Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-22T12:01:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_GabrieleGroehsGuerreiro.pdf: 3199151 bytes, checksum: 756703b7a0674b416dcb2ff9e0f31bfd (MD5) / Made available in DSpace on 2018-08-22T12:01:53Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_GabrieleGroehsGuerreiro.pdf: 3199151 bytes, checksum: 756703b7a0674b416dcb2ff9e0f31bfd (MD5) Previous issue date: 2018-02-20 / Cerebral palsy (CP) is a permanent condition resulting from a non-progressive injury of the immature brain, which affects posture and movement, and may be accompanied by disturbances of cognition, perception, sensation, behavior, epilepsy, among others. Children and adolescents with this condition are more likely to develop oral diseases such as tooth decays, periodontal disease, bruxism and malocclusion. In this context, the objective of the present study was to evaluate the oral health conditions of individuals with cerebral palsy, as well as the perception of their caregivers regarding the oral health of children and adolescents, and whether these conditions are associated with the motor impairment of these individuals. An observational cross-sectional study was carried out from February 2017 to August 2017 in three reference centers in the treatment of individuals with CP in the central region of the state of Rio Grande do Sul, Brazil. The sample was composed by 35 children and adolescents with CP and their caregivers. The motor function was evaluated through the application of two instruments, GMFCS and GMFM88. For the assessment of oral health, indexes such as DMFT, IPV, Malocclusion, Dental Age, pH, Buffering Capacity, and Saliva Flow were evaluated. A semi-structured questionnaire with open and closed questions was used to evaluate socio-demographic data and the caregiver's perception regarding oral health. In this study, 65.7% of the children and adolescents were quadriplegic, 88.6% with spastic tone, the mother being their main caregiver and the main responsible for the oral hygiene. It is possible to observe a significant association (p < 0,05) between GMFCS categorized according to locomotion dependence and the presence of malocclusion, but not with gross motor function (GMFM88). It has been found that patients with altered dental age have a lower GMFM88 index than those with dental age within the normal range. In the assessment of the perception of oral health, caregivers of quadriplegic patients, wheelchair users and with greater impairment of gross motor function (GMFM88) perceive more oral alterations. However, it can be concluded that malocclusion and dental age are associated with gross motor function (GMFCS and GMFM88) and dental caries has been associated with better GMFM scores88. / A paralisia cerebral (PC) é uma condição permanente, resultante de uma lesão não progressiva do encéfalo imaturo, que afeta a postura e o movimento, podendo estar acompanhada de distúrbios de cognição, percepção, sensação, comportamento, epilepsia, entre outros. Crianças e adolescentes com essa condição tem maior propensão a desenvolverem doenças bucais como cárie dentária, doença periodontal, bruxismo e má oclusão. Nesse contexto, o objetivo do presente trabalho foi avaliar as condições de saúde bucal de indivíduos com paralisia cerebral, bem como a percepção dos seus cuidadores em relação à saúde bucal das crianças e adolescentes e se estas condições estão associadas com o comprometimento motor desses indivíduos. Foi realizado um estudo transversal observacional no período de fevereiro de 2017 a agosto de 2017 em três centros de referência em tratamento de indivíduos com PC na região central do estado do Rio Grande do Sul, Brasil. A amostra foi composta por 35 crianças e adolescentes com PC e seus cuidadores. A função motora foi avaliada através da aplicação de dois instrumentos, o GMFCS e o GMFM88. Para a aferição da saúde bucal foram avaliados os índices de CPOD, IPV, Má oclusão, Idade dentária, pH, Capacidade de tampão e Fluxo da saliva. Para avaliação de dados sócio-demográficos e percepção do cuidador em relação à saúde bucal foi utilizado um questionário semi-estruturado com perguntas abertas e fechadas. No presente estudo 65,7% das crianças e adolescentes apresentaram-se quadriplégicas, 88,6% com tônus espástico, sendo a mãe seu principal cuidador e o principal responsável pela higienização bucal. Pode-se verificar uma associação significativa (p < 0,05) entre o GMFCS categorizado de acordo com a dependência para locomoção e a presença de má oclusão, mas não com a função motora grossa (GMFM88). Verificou-se que pacientes com idade dentária alterada apresentam o índice GMFM88 menor do que os que apresentam idade dentária dentro dos padrões normais. Na avaliação da percepção da saúde bucal, cuidadores de pacientes quadriplégicos, cadeirantes e com maior comprometimento da função motora grossa (GMFM88) percebem mais alterações bucais. Contudo pode-se concluir que má-oclusão e idade dentária estão associadas com a função motora grossa (GMFCS e GMFM88) e cárie dentária foi associada a melhores escores de GMFM88.