RESUMO
Nonhuman primates (NHPs) are important to study the pathophysiology of neurodegenerative disease and evaluate therapies targeting the central nervous system (CNS). Understanding the age-associated incidence of natural CNS pathology in a given NHP species is critical to assess the safety of potential treatments for neurodegenerative disorders like Alzheimer's disease (AD). We describe background and age-related neuropathology in the St. Kitts African green monkey (AGM), a recognized translational model for neurodegenerative research, additionally defining the age progression of AD-associated neuropathology in this species. Seventy-one AGM brains were examined, representing age groups of 3-6 years (n = 20), 7-9 years (n = 20), 10-15 years (n = 20), and >15 years (n = 11). A subset of brains (n = 31) was assessed immunohistochemically for AD-related pathology, including expressions of Aß, tau, and GFAP. Age-related microscopic findings included hemosiderosis, spheroid formation, neuronal lipofuscinosis and neuromelanosis, white matter and neuropil vacuolation, astrocytosis, and focal microgliosis. Non-age-related findings included perivascular ceroid-laden macrophages, meningeal melanosis, and vascular mineralization. Immunohistochemistry revealed 4G8-immunopositive Aß plaques and vascular deposits in the prefrontal, frontal, cingulate, and temporal cortices of nine animals over 15 years of age, with associated increase in GFAP expression. In 12 animals, 11 over the age of 10 years, phosphorylated tau CP13-immunoreactive neurons, neuropil, and oligodendrocyte-like cells were seen in the prefrontal, frontal, cingulate, orbital, temporal, and entorhinal cortices as well as the hippocampus; no neurofibrillary tangles were observed. AD-related pathology showed an age-related development in cognitive-associated areas in the AGM, highlighting the value of the AGM as a natural model for these neurodegenerative diseases.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Chlorocebus aethiops , Doença de Alzheimer/patologia , Proteínas tau/metabolismo , Peptídeos beta-Amiloides , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Encéfalo/metabolismo , Envelhecimento/patologiaRESUMO
BACKGROUND: Toxoplasma gondii is a worldwide protozoan parasite of felids which can infect almost all warm-blooded animals, including humans. Free-roaming chickens are good indicators of environmental contamination with T. gondii oocysts because they feed from the ground. Previous research has demonstrated a high seroprevalence of T. gondii in domestic animals on St. Kitts but little is known about the genotypes circulating in the environment. METHODS: Hearts and brains from 81 free-roaming chickens in St. Kitts were digested and inoculated into 243 Swiss Webster mice in a bioassay. DNA was extracted from digested chicken tissues and the brains of all mice, and screened for T. gondii. Positive samples were genotyped using restriction fragment length polymorphism. Chicken sera were also screened for T. gondii antibodies using a modified agglutination test (MAT). RESULTS: Overall, 41% (33 out of 81) of chickens were positive for T. gondii either by serology and/or by PCR. Antibodies to T. gondii were detected by MAT in 32% (26 out of 81) of chickens, and T. gondii DNA was detected in mouse brains representing 26% (21 out of 81) of chickens. Genotyping of 21 DNA isolates, using polymorphisms at 10 loci, including SAG1, SAG2 (5'-3' SAG2 and alt.SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico, revealed that 7 were ToxoDB genotype #141, 6 were #1 (Type II), 3 were #13, 3 were #265, one was #264 and one was #2 (Type III). Genotypes #13 and #141 appear to be more virulent. CONCLUSIONS: The results of this study highlight the greater genetic diversity of T. gondii circulating in the Caribbean region, with potentially different degrees of virulence to humans.