Investigating the wire fraction of the neuropil in primate cerebral ortex

D. Phil., School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 2011Whether the neuropil is a static, optimally wired entity, whose components must be balanced in a certain way, is an open question. Are the proportions of the components of the neuropil consistent across different mammalian cortices, especially in primates where the cerebral cortex is complexly organized? This question is interesting because the actual biological underpinnings of complex behaviours and intelligence in big-brained primates remain enigmatic and why they seem qualitatively different from other animals in terms of their cognitive abilities. Understanding changes that may have occurred in the brain, especially at the level of neuropil organization, during the evolution in primates is important to our growing understanding of the intellectual abilities and behaviours exhibited by members of this group. The current series of quantitative studies was aimed at investigating variations in the proportionality of the “wire fraction” in three primate species, the olive baboon (Papio anubis), vervet monkey (Cercopithecus aethiops) and the common chimpanzee (Pan troglodytes), in a range of higher and lower order cortical areas, using a newly developed method that involves standard and immunohistochemical staining techniques to reveal and quantify the various profiles of the fine structures of the cerebral cortex. The results of these studies demonstrate clear layer differences in the wire fraction of the cerebral cortex, and for the most part, consistency in the neuropil wire fraction of the same layer across areas of the cerebral cortex within and between individuals of the same species; however, differences in the wire fraction of the neuropil were associated with changes in brain size. It is apparent that the neuropil is not static, as wiring “optimality” changes with layers and brain size and this has functional implications regarding neuronal processing and behavioural outcomes. The adaptive rationale adopted by evolutionary psychology studies to explain behaviours may be erroneous, as adaptation does not always explain sufficiently the emergence of complex behaviours related to brain size increases, especially in primates

Coenzyme Q10 Protect Mice Against Inflammatory Responses During Experimental Cerebral Malaria

Malaria is a life threatening infectious diseases transmitted by the bite of infected female Anopheles mosquito and responsible for high morbidity and mortality rates. Cerebral malaria is a complex neurological syndrome, whose pathology is mediated by inflammatory processes triggered by the immune system of the host following infection with Plasmodium falciparum. Coenzyme Q10 is an obligatory cofactor in the electron transport chain. The reduced form of Coenzyme Q10 serves as a potent antioxidant additionally; Coenzyme Q10 has been identified as a modulator of gene expression, inflammation and apoptosis. However, the modulatory effects of Coenzyme Q10 Plasmodium berghei ANKA infection process and risk occurrence of experimental cerebral malaria (ECM) have not been determined. The aim of this study was to elucidate the putative impact of oral administration of Coenzyme-Q10 on the initiation or regulation of inflammatory immune response in ECM of C57BL/6 mice during Plasmodium berghei ANKA (PbA) infection. We observed that oral administration of Coenzyme-Q10 both before and after PbA infection significantly hampered infiltration of inflammatory monocytes into the brain. Furthermore, pro-inflammatory cytokine TNF-α, which is associated with inflammation during ECM, was down-regulated in Coenzyme-Q10 administered mice. Remarkably, Coenzyme-Q10 was very effective in inhibiting dendritic cell differentiation. These data collectively demonstrated the immuno-modulatory function of Coenzyme-Q10 on host inflammatory responses during ECM. Keywords: Plasmodium berghei ANKA, Coenzyme Q10, experimental cerebral malaria DOI: 10.7176/JNSR/9-2-05

Successful experimental infant baboon model for childhood cryptosporidiosis studies

Abstract Background Cryptosporidiosis causes high morbidity and mortality in children under 2 years of age globally. The lack of an appropriate animal model that mimics the pathogenesis of disease in humans has hampered the development and testing of potential therapeutic options. This study aimed to develop and validate an infant baboon infection model of cryptosporidiosis. Methods Eighteen immunocompetent weaned infant baboons aged 12 to 16 months were used. The animals were n = 3 controls and three experimental groups of n = 5 animals each inoculated with Cryptosporidium parvum oocysts as follows: group 1: 2 × 104, group 2: 2 × 105, group 3: 2 × 106 followed by daily fecal sampling for oocyst evaluation. Blood sampling for immunological assay was done on the day of infection and weekly thereafter until the end of the experiment, followed by necropsy and histopathology. Statistical analysis was performed using R, SPSS, and GraphPad Prism software. Analysis of variance (ANOVA) and Bonferroni post hoc tests were used for comparison of the means, with p < 0.05 considered as a significant difference. Correlation coefficient and probit analysis were also performed. Results In all experimental animals but not controls, the onset of oocyst shedding occurred between days 2 and 4, with the highest oocyst shedding occurring between days 6 and 28. Histological analysis revealed parasite establishment only in infected animals. Levels of cytokines (TNF-α, IFN-γ, and IL-10) increased significantly in experimental groups compared to controls. Conclusion For developing a reproducible infant baboon model, 2 × 104 oocysts were an effective minimum quantifiable experimental infection dose. Graphic abstrac

Nuclear organization of cholinergic, putative catecholaminergic and serotonergic systems in the brains of two megachiropteran species

The nuclear organization of the cholinergic, putative catecholaminergic and serotonergic systems within the brains of the megachiropteran straw-coloured fruit bat (Eidolon helvum) and Wahlberg's epauletted fruit bat (Epomophorus wahlbergi) were identified following immunohistochemistry for cholineacetyltransferase, tyrosine hydroxylase and serotonin. The aim of the present study was to investigate possible differences in the nuclear complement of the neuromodulatory systems of these species in comparison to previous studies on megachiropterans, microchiropterans and other mammals. The nuclear organization of these systems is identical to that described previously for megachiropterans and shows many similarities to other mammalian species, especially primates; for example, the putative catecholaminergic system in both species presented a very compact nucleus within the locus coeruleus (A6c) which is found only in megachiropterans and primates. A cladistic analysis of 38 mammalian species and 82 characters from these systems show that megachiropterans form a sister group with primates to the exclusion of other mammals, including microchiropterans. Moreover, the results indicate that megachiropterans and microchiropterans have no clear phylogenetic relationship to each other, as the microchiropteran systems are most closely associated with insectivores. Thus a diphyletic origin of Chiroptera is supported by the present neural findings

Nuclear organization of cholinergic, putative catecholaminergic and serotonergic systems in the brains of five microchiropteran species

The current study describes, using immunohistochemical methods, the nuclear organization of the cholinergic, catecholaminergic and serotonergic systems within the brains of five microchiropteran species. For the vast majority of nuclei observed, direct homologies are evident in other mammalian species; however, there were several distinctions in the presence or absence of specific nuclei that provide important clues regarding the use of the brain in the analysis of chiropteran phylogenetic affinities. Within the five species studied, three specific differences (presence of a parabigeminal nucleus, dorsal caudal nucleus of the ventral tegmental area and the absence of the substantia nigra ventral) found in two species from two different families (Cardioderma cor; Megadermatidae, and Coleura afra; Emballonuridae), illustrates the diversity of microchiropteran phylogeny and the usefulness of brain characters in phylogenetic reconstruction. A number of distinct differences separate the microchiropterans from the megachiropterans, supporting the diphyletic hypothesis of chiropteran phylogenetic origins. These differences phylogenetically align the microchiropterans with the heterogenous grouping of insectivores, in contrast to the alignment of megachiropterans with primates. The consistency of the changes and stasis of neural characters with mammalian phylogeny indicate that the investigation of the microchiropterans as a sister group to one of the five orders of insectivores to be a potentially fruitful area of future research

Sustainable education and training in laboratory animal science and ethics in low- and middle-income countries in Africa – challenges, successes, and the way forward

Despite the recognised need for education and training in laboratory animal science (LAS) and ethics in Africa, access to such opportunities has historically been limited. To address this, the Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE) was established to pioneer a support network for the development of education and training in LAS and ethics across the African continent. In the 4.5 years since the establishment of PAN-LASE, 3635 individuals from 28 African countries have participated in our educational activities. Returning to their home institutions, they have both established and strengthened institutional and regional hubs of knowledge and competence across the continent. Additionally, PAN-LASE supported the development of guidelines for establishment of institutional Animal Ethics Committees, a critical step in the implementation of ethical review processes across the continent, and in enhancing animal welfare and scientific research standards. Key challenges and opportunities for PAN-LASE going forward include the formalisation of the network; the sustainability of education and training programmes; implementation of effective hub-and-spoke models of educational provision; strengthening governance frameworks at institutional, national and regional levels; and the availability of Africa-centric open access educational resources. Our activities are enhancing animal welfare and the quality of animal research undertaken across Africa, enabling African researchers to undertake world-leading research to offer solutions to the challenges facing the continent. The challenges, successes and the lessons learnt from PAN-LASE’s journey are applicable to other low- and middle-income countries across the world seeking to enhance animal welfare, research ethics and ethical review in their own country or region