Cobalt-induced neuro-behavioural alterations are accompanied by profound Purkinje cell and gut-associated responses in rats.

Metal ions including cobalt (Co) ions reportedly exhibit neurotoxic and antimicrobial properties. We hypothesized that oral exposure to Co may have implications for gut-dysbiosis with possible alterations of microbiota-gut-brain signaling in the host. In this preliminary study, we sought to examine whether exposure of male Wistar rats to cobalt chloride (CoCl2) at 0, 25, 50 and 100 mg/kg for two weeks affects select neurobehavioural indices, vagus nerve and brain morphology along with evaluation of associated changes in faecal bacterial flora, faecal fatty acids and the morphology of the intestines. CoCl2-exposed rats showed a dose-dependent reduction in hanging latency in the hanging wire (HW) test, reduced tendency to recognize novel objects in a Novel Object recognition (NOR) test, but increased interaction with open arms in the elevated plus maze (EPM) test, compared to controls. There were dose-dependent reductions in total heterotrophic count, coliforms, E. coli, Enterococcal and Lactobacilli counts in the faeces. Administration of CoCl2 at 100 mg/kg evoked the appearance of unsaturated fatty acids including palmitoleic, oleic and linoleic acids in the faeces as detected by gas chromatography-flame ion detection (GD-FID) analysis using fatty acid methyl esters (FAME) standards. Histopathological examination revealed chromatolysis of Purkinje cells in the cerebellum, although no significant lesions were present in the vagus nerve isolated from all the groups. In the intestines, there was moderate to severe infiltration of inflammatory cells into the duodenum, ileum, jejunum and colon while villi erosions were seen prominently in the ileum. These initial findings suggest that short-term exposure to Co can lead to gut-associated changes that may underlie neurotoxicity and alterations in behavior induced by Co.

Neuropathological profile of the African Giant Rat brain (Cricetomys gambianus) after natural exposure to heavy metal environmental pollution in the Nigerian Niger Delta.

Pollution by heavy metals is a threat to public health because of the adverse effects on multiple organ systems including the brain. Here, we used the African giant rat (AGR) as a novel sentinel host to assess the effect of heavy metal accumulation and consequential neuropathology upon the brain. For this study, AGR were collected from distinct geographical regions of Nigeria: the rain forest region of south-west Nigeria (Ibadan), the central north of Nigeria (Abuja), and in oil-polluted areas of south Nigeria (Port-Harcourt). We found that zinc, copper, and iron were the major heavy metals that accumulated in the brain and serum of sentinel AGR, with the level of iron highest in animals from Port-Harcourt and least in animals from Abuja. Brain pathology, determined by immunohistochemistry markers of inflammation and oxidative stress, was most severe in animals from Port Harcourt followed by those from Abuja and those from Ibadan were the least affected. The brain pathologies were characterized by elevated brain advanced oxidation protein product (AOPP) levels, neuronal depletion in the prefrontal cortex, severe reactive astrogliosis in the hippocampus and cerebellar white matter, demyelination in the subcortical white matter and cerebellar white matter, and tauopathies. Selective vulnerabilities of different brain regions to heavy metal pollution in the AGR collected from the different regions of the country were evident. In conclusion, we propose that neuropathologies associated with redox dyshomeostasis because of environmental pollution may be localized and contextual, even in a heavily polluted environment. This novel study also highlights African giant rats as suitable epidemiological sentinels for use in ecotoxicological studies.

Neocortex neurogenesis and maturation in the African greater cane rat.

BACKGROUND: Neocortex development has been extensively studied in altricial rodents such as mouse and rat. Identification of alternative animal models along the "altricial-precocial" spectrum in order to better model and understand neocortex development is warranted. The Greater cane rat (GCR, Thyronomys swinderianus) is an indigenous precocial African rodent. Although basic aspects of brain development in the GCR have been documented, detailed information on neocortex development including the occurrence and abundance of the distinct types of neural progenitor cells (NPCs) in the GCR are lacking. METHODS: GCR embryos and fetuses were obtained from timed pregnant dams between gestation days 50-140 and their neocortex was analyzed by immunofluorescence staining using characteristic marker proteins for NPCs, neurons and glia cells. Data were compared with existing data on closely related precocial and altricial species, i.e. guinea pig and dwarf rabbit. RESULTS: The primary sequence of neuro- and gliogenesis, and neuronal maturation is preserved in the prenatal GCR neocortex. We show that the GCR exhibits a relatively long period of cortical neurogenesis of 70 days. The subventricular zone becomes the major NPC pool during mid-end stages of neurogenesis with Pax6 + NPCs constituting the major basal progenitor subtype in the GCR neocortex. Whereas dendrite formation in the GCR cortical plate appears to initiate immediately after the onset of neurogenesis, major aspects of axon formation and maturation, and astrogenesis do not begin until mid-neurogenesis. Similar to the guinea pig, the GCR neocortex exhibits a high maturation status, containing neurons with well-developed dendrites and myelinated axons and astrocytes at birth, thus providing further evidence for the notion that a great proportion of neocortex growth and maturation in precocial mammals occurs before birth. CONCLUSIONS: Together, this work has deepened our understanding of neocortex development of the GCR, of the timing and the cellular differences that regulate brain growth and development within the altricial-precocial spectrum and its suitability as a research model for neurodevelopmental studies. The timelines of brain development provided by this study may serve as empirical reference data and foundation in future studies in order to model and better understand neurodevelopment and associated alterations.

Morphometric analysis of the spinal cord of the Sus scrofa (large white and landrace crossbreed).

The incidence of spinal cord (SC) injury in developed and undeveloped countries is alarming. The pig (Sus scrofa) has been recommended as a suitable research model for translational studies because of its morphophysiological similarities of organ systems with humans. There is a dearth of information on the SC anatomy of the large white and landrace crossbreed (LW-LC) pigs. We therefore aim to describe the gross morphology and morphometry of its SC. Twelve juvenile LW-LC pigs (six males and six females) were used. The skin and epaxial muscles were dissected to expose the vertebral column. The SC was carefully harvested by laminectomy, and 13 gross SC morphometric parameters were evaluated. Thirty-three spinal nerves were seen emanating from either side of the SC by means of dorsal and ventral spinal roots. The overall average of SC length and weight was 36.23 ± 1.01 cm and 16.60 ± 0.58 g, respectively. However, the mean SC length and weight were higher in females compared with males, with SC weight being statistically significant. A positive relationship between SC length and weight was significant for males (p = 0.0435) but not for females (p = 0.42). Likewise, the strength of the relationship between SC length and weight was significant in males (r = 0.82) but not significant in females (r = 0.41). Baseline data for the morphometric features of the spinal cord in the LW-LC pigs were generated, which will contribute to the knowledge of this species anatomy and useful information on regional anaesthesia that should further strengthen the drive in adopting the pig as a suitable research model for biomedical research.

Cerebellar and Olfactory Bulb Perturbations Induced by Vanadium Neurotoxicity in the African Giant Rat (Cricetomys gambianus, Waterhouse).

The African giant rat, AGR (Cricetomys gambianus) is a unique rodent known for its keen sense of smell which has enabled its use in the diagnosis of tuberculosis and demining activities in war torn countries. This keen sense of smell and the ability to navigate tight spaces are skills modulated by the olfactory bulb and cerebellum. While the brain is generally susceptible to environmental pollutants such as heavy metals, vanadium has predilection for these two brain regions. This work was thus designed to investigate the probable neurotoxic effect of vanadium on the neuronal cytoarchitecture of the cerebellum and olfactory bulb in this rodent. To achieve this, twelve adults male AGRs were divided into two groups (vanadium and control groups) and were given intraperitoneal injections of 3mg/kg body weight sodium metavanadate and normal saline respectively for 14 days. After which they were sacrificed, and brains harvested for histological investigations using Nissl and Golgi staining techniques. Results from our experiment revealed Purkinje cell degeneration and pyknosis as revealed by a lower intact-pyknotic cell (I-P) ratio, higher pyknotic Purkinje cell density and poor dendritic arborizations in the molecular layer of the cerebellum in the vanadium treated group. In the olfactory bulb, neuronal loss in the glomerular layer was observed as shrunken glomeruli. These neuronal changes have been linked to deficits in motor function and disruption of odor transduction in the olfactory bulb. This work has further demonstrated the neurotoxic effects of vanadium on the cerebellum and olfactory bulb of the AGR and the likely threat it may pose to the translational potentials of this rodent. We therefore propose the use of this rodent as a suitable model for better understanding vanadium induced olfactory and cerebellar dysfunctions.

Astrocytes and Microglia in Stress-Induced Neuroinflammation: The African Perspective.

Background: Africa is laden with a youthful population, vast mineral resources and rich fauna. However, decades of unfortunate historical, sociocultural and leadership challenges make the continent a hotspot for poverty, indoor and outdoor pollutants with attendant stress factors such as violence, malnutrition, infectious outbreaks and psychological perturbations. The burden of these stressors initiate neuroinflammatory responses but the pattern and mechanisms of glial activation in these scenarios are yet to be properly elucidated. Africa is therefore most vulnerable to neurological stressors when placed against a backdrop of demographics that favor explosive childbearing, a vast population of unemployed youths making up a projected 42% of global youth population by 2030, repressive sociocultural policies towards women, poor access to healthcare, malnutrition, rapid urbanization, climate change and pollution. Early life stress, whether physical or psychological, induces neuroinflammatory response in developing nervous system and consequently leads to the emergence of mental health problems during adulthood. Brain inflammatory response is driven largely by inflammatory mediators released by glial cells; namely astrocytes and microglia. These inflammatory mediators alter the developmental trajectory of fetal and neonatal brain and results in long-lasting maladaptive behaviors and cognitive deficits. This review seeks to highlight the patterns and mechanisms of stressors such as poverty, developmental stress, environmental pollutions as well as malnutrition stress on astrocytes and microglia in neuroinflammation within the African context.

Morphological Characterization of the Developing Greater Cane Rat (Thryonomys swinderianus) Brain.

Developmental mode along the altricial-precocial spectrum is well known to be influenced by brain development and maturation. The greater cane rat (GCR) is an indigenous precocial African rodent with uncommon phenotypes and life traits. This study was therefore designed to characterize and describe distinctive external developmental features in the prenatal GCR brain across the entire gestational length using the emergence and differentiation of external features of the brain vesicles. Four gross morphometric brain parameters (weight, length, width, and height) were evaluated and expressed as mean ± SEM. Relationship between all brain morphometrics and gestation length were analyzed using one-way ANOVA and linear regression. Developmental milestones in the prenatal GCR were then compared with closely related precocial mammals. The earliest time point with gross observable features in the prenatal GCR brain was at gestation day (GD) 60. The period with the most remarkable gross developmental features was noted between GD80 and GD100. Some of these gross features include differentiation of the cerebellar plate into vermis and lateral lobes, emergence of the piriform lobes, mammillary bodies, colliculi bodies, cerebral peduncles, and primordial pons. By GD130, most gross topographic neural features were already established. Cerebellar lobation and patterning at GD130 were the last recognizable gross developmental features noticed in the prenatal GCR brain. This coincided with the time of first eye opening in the GCR fetus. The developmental pattern observed in the prenatal GCR brain is similar to those noted in precocial rodent like the guinea pig. However, the onset of these milestones was delayed, and their duration was relatively shorter in the GCR. This study provides a frame of baseline reference of morphological brain features in the GCR embryos and fetuses that will be useful for fetal age estimation, for home grown neurodevelopmental and eco-toxicological studies, as this rodent is being proposed as a research model.

A study of scientific publications on the greater cane rat (Thryonomys swinderianus, Temminck 1827).

BACKGROUND: The greater cane rat (GCR), reputed to be African's second largest rodent, is a precocial hystricomorph with an uncommon phenotype and life history. Scientific and socio-economic interests in the GCR have led to heightened research efforts targeted towards a better understanding of its biology and exploration of its economic and translational usefulness. METHODS: Records of all online scientific publications on the GCR from Google, Google Scholar, PubMed, science.gov, Ebscohost and Worldwide science, with the exception of research theses, proceedings, unpublished projects and abstracts, were collated and analyzed using descriptive statistics. RESULTS: A total of 146 published scholarly articles spanning about six decades were retrieved, with 98% of the GCR publications originating from African countries. Nigeria boasts the highest number of publications (58.22%) followed by Ghana (21.23%) and South Africa (5.48%) while Senegal contributed the least (0.69%). Publications were sorted into ten field categories. The field with the highest number of articles (41.78%) was animal breeding and management recording, closely followed by anatomy (37.67%). Lesser contributions were made by parasitology (5.48%), biochemistry/hematology (4.8%), pharmacology/toxicology (4.11%), pathology (2.06%), and surgery/anesthesia and physiology (1.37% apiece). The fields with fewest contributions were microbiology and developmental biology (0.69% each). CONCLUSION: This study chronicles the spectrum of knowledge available on the GCR, highlighting the knowledge gap that still exists in various fields in order to provide advocacy for new frontiers in research efforts on this rodent. We suggest the need for a clearly defined and well integrated national/regional policy aimed at establishing Africa's foremost micro-livestock rodent, the greater cane rat, on the world's scientific radar.

Cytoarchitecture of the Hippocampal Formation in the African Giant Rat (Cricetomys gambianus, Waterhouse).

The African Giant Rat, AGR is an indigenous nocturnal rodent noted for its unique olfactory and cognitive abilities. They have been deployed more recently in the detection of landmines and diagnosis of tuberculosis - two scourges that have had a tremendous negative impact on the African landscape. This olfactory-aided cognition has been linked to the hippocampus. While the anatomical infrastructure of the olfactory bulb of the AGR has been elucidated, little is known about the adaptive cytoarchitecture of the AGR hippocampal formation. This study describes the histological features, including subfields and stratifications of the AGR hippocampus using Nissl and Golgi stains. The basic cytoarchitecture of the AGR hippocampus observed in this study, with respect to stratification, subfields and cell types, is similar to those reported in the laboratory rats. Cell types identified in the AGR hippocampus include pyramidal cells, granule cells and mossy cells with mossy fibers and Schaffer collaterals also delineated. Hippocampal proper subfields CA1 to CA4 were identified. CA3 pyramidal neurons formed a well-defined cell layer starting in between the upper and lower ends of the dentate gyrus and had larger, more distinct pyramidal cells and higher cell layer thickness (240.0±6.0 µm) relative to subfields CA1 (87.0±2.0 µm) and CA2 (109.0±4.20 µm) with significant statistical differences at p<0.001. The detailed, delicate arrangement of various cell types and subfields, intricate wiring with synapses and laminar organization of the hippocampal formation noticed in the AGR strongly supports the canonical trisynaptic circuitry of the hippocampus. It will however be necessary to carry out densitometric studies and detailed neurochemical profiling of the AGR hippocampus to fully elucidate the functional leverage of this unique rodent. We, therefore, suggest the suitability of this rodent as a model for olfaction-linked memory studies.

Developmental horizons in the pre-natal development of the Greater cane rat (Thryonomys swinderianus).

The Greater cane rat (GCR, Thyronomys swinderianus) is a precocial rodent predominantly found within Africa. Economic and scientific interests have led to several research efforts towards the domestication and better understanding of the biology and development of this rodent. Despite these efforts, information on the pre-natal development of this rodent is currently lacking. This study characterises distinct developmental milestones including skin pigmentation, emergence and distributions of hairs, calvarium consistency, teeth eruption, development of appendages, sensory organs and external genitalia in the pre-natal GCR and assesses quantitative body parameters, that is body weight, body and crown-rump lengths across its entire gestation length (gestation days [GDs] 10-140). Using these external features, we provide baseline reference ontogenetic scales for GCR embryos and fetuses, employable for stage, age and sex estimation of the pre-natal GCR in future studies. We observed that the first evidence of an embryo was not seen before the end of the first trimester (GD50) and that the late second trimester (GD80-GD100) marks the transition from embryogenesis to fetogenesis in the GCR. As both events occur at a much later developmental time point when compared to precocial non-rodents including human, sheep and pig and slightly later when compared to other precocial rodents such as guinea pig, our data provide first indication that the pre-natal GCR development might be associated with a reproductive delay. Together, this study expands our knowledge of the development and biology of the GCR, which will improve reproductive and breeding management, and native species conservation of this hystricomorph mammal.

Peripheral axonopathy in sciatic nerve of adult Wistar rats following exposure to vanadium.

Depletion of myelin and neurobehavioural deficits are indications that vanadium crosses the blood-brain barrier and such neurotoxic effects of vanadium on the brain of Wistar rats have been elucidated. The effect however on the peripheral nerves, is yet to be reported. Thus, this work was designed to evaluate the axonal and myelin integrity of sciatic nerves in Wistar rats following exposure to vanadium. Ten male Wistar rats were exposed to 3 mg/kg body weight of sodium metavanadate for 7 days, subjected to rearing and forelimb grip behavioural tests, and sciatic nerves processed for histology (haematoxylin and eosin, cresyl violet, and luxol fast blue). Dystrophic axons with vesiculated myelin, thinned myelin sheath, and demyelinated axons were observed in the vanadium exposed rats, suggestive of axonopathy, classified as fourth-degree nerve injury. Lower behavioural scores were recorded for vanadium-dosed rats; thus, corroborating histological pictures observed of the sciatic nerves. Authors posit that vanadium crossed the "blood-nerve" barrier and caused the observed axonal pathologies and myelin depletion in the sciatic nerves of these rodents with resultant motor deficits. The present paper discusses possible motor deficits and the likely public health importance in regions with crude oil pollution and gas flaring rich in vanadium products.

Astrocyte morphology, heterogeneity, and density in the developing African giant rat (Cricetomys gambianus).

Astrocyte morphologies and heterogeneity were described in male African giant rats (AGR; Cricetomys gambianus, Waterhouse) across three age groups (five neonates, five juveniles, and five adults) using Silver impregnation method and immunohistochemistry against glial fibrillary acidic protein. Immunopositive cell signaling, cell size and population were least in neonates, followed by adults and juveniles, respectively. In neonates, astrocyte processes were mostly detected within the glia limitans of the mid and hind brain; their cell bodies measuring 32 ± 4.8 µm in diameter against 91 ± 5.4 µm and 75 ± 1.9 µm in juveniles and adults, respectively. Astrocyte heterogeneity in juvenile and adult groups revealed eight subtypes to include fibrous astrocytes chiefly in the corpus callosum and brain stem, protoplasmic astrocytes in the cortex and dentate gyrus (DG); radial glia were found along the olfactory bulb (OB) and subventricular zone (SVZ); velate astrocytes were mainly found in the cerebellum and hippocampus; marginal astrocytes close to the pia mater; Bergmann glia in the molecular layer of the cerebellum; perivascular and periventricular astrocytes in the cortex and third ventricle, respectively. Cell counts from twelve anatomical regions of the brain were significantly higher in juveniles than in adults (p ≤ 0.01) using unpaired student t-test in the cerebral cortex, pia, corpus callosum, rostral migratory stream, DG, and cerebellum. Highest astrocyte count was found in the DG, while the least count was in the brain stem and sub cortex. Astrocytes along the periventricular layer of the OB are believed to be part of the radial glia system that transport newly formed cells towards the hippocampus and play roles in neurogenesis migration and homeostasis in the AGR. Therefore, astrocyte heterogeneity was examined across age groups in the AGR to determine whether age influences astrocytes population in different regions of the AGR brain and discuss possible functional roles.

Neurobehavioral and cytotoxic effects of vanadium during oligodendrocyte maturation: a protective role for erythropoietin.

Vanadium exposure has been known to lead to lipid peroxidation, demyelination and oligodendrocytes depletion. We investigated behaviour and glial reactions in juvenile mice after early neonatal exposure to vanadium, and examined the direct effects of vanadium in oligodendrocyte progenitor cultures from embryonic mice. Neonatal pups exposed to vanadium via lactation for 15 and 22 days all had lower body weights. Behavioural tests showed in most instances a reduction in locomotor activity and negative geotaxis. Brain analyses revealed astrocytic activation and demyelination in the vanadium exposed groups compared to the controls. In cell culture, exposure of oligodendrocytes to 300 µM sodium metavanadate significantly increased cell death. Expression of the oligodendrocyte specific proteins, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and oligodendrocyte specific protein (OSP/Claudin) were reduced upon vanadium treatment while simultaneous administration of erythropoietin (EPO; 4-12 U/ml) counteracted vanadium-toxicity. The data suggest that oligodendrocyte damage may explain the increased vulnerability of the juvenile brain to vanadium and support a potential for erythropoietin as a protective agent against vanadium-toxicity during perinatal brain development and maturation.

The vertebral column, ribs, and sternum of the African giant rat (Cricetomys gambianus waterhouse).

Examined bones were obtained from eight adult African giant rats, Cricetomys gambianus Waterhouse. Animals used had an average body mass of 730.00 ± 41.91 gm and body length of 67.20 ± 0.05 cm. The vertebral formula was found to be C7, T13, L6, S4, Ca31-36. The lowest and highest points of the cervicothoracic curvature were at C5 and T2, respectively. The spinous process of the axis was the largest in the cervical group while others were sharp and pointed. The greatest diameter of the vertebral canal was at the atlas (0.8 cm) and the lowest at the caudal sacral bones (2 mm). The diameter of the vertebral foramen was the largest at C1 and the smallest at the S4; the foramina were negligibly indistinct caudal to the sacral vertebrae. There were 13 pairs of ribs. The first seven pairs were sternal, and six pairs were asternal of which the last 2-3 pairs were floating ribs. The sternum was composed of deltoid-shaped manubrium sterni, four sternebrae, and a slender processus xiphoideus. No sex-related differences were observed. The vertebral column is adapted for strong muscular attachment and actions helping the rodent suited for speed, agility, dexterity, and strength which might enable it to overpower prey and escape predation.

Macro-anatomical investigations of the skeletons of the African giant rat (Cricetomys gambianus Waterhouse 1840) II: Fore limb

In this study, 7 African giant rats (Cricetomysgambianus Waterhouse 1840) were used to investigate the bony fore limb. It was observed that the supraspinous fossa was larger than the infraspinous fossa. The slender, curved clavicles were about 2.53 cm long. The humerus was peculiar and the ridges and the tuberosities were well developed. There was a supracondylar foramen in the mediodistal region of the humerus in all the rats, while 3of the rats (42.9%) had a supratrochlear foramen. The radius and ulna were distinct but appeared fused in most of the African giant rats used in this study. In the carpal proximal row, radial carpal and intermediate carpal bones were fused to form the Os carpi intermedioradiale. The manus was complete, with five digits. There were two phalanges in the first digit and the other four digits were composed of three phalanges. On the palmar face of the man us there were radial and ulnar sessamoids (ossa sessamoidea palmaria) with an irregular surface. In conclusion, there were some prominent features in the forelimb bones of the African giant rat that typifies them asfast running, burrowing and shoveling rodents (AU)

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Macro-anatomical investigations of the skeletons of the African giant rat (Cricetomys gambianus Waterhouse): Pelvic limb

In this study, the hind limb bones of adult African giant rats (Cricetomys gambianus Waterhouse)were used to investigate their gross morphology. The ventrocaudal iliac spine was absent in the animals while the pelvic symphysis was fused. The average distance between the mid-acetabulum and the tuber coxae was41.00 mm, and the average distance between the mid-acetabulum and the ischial tuberosity (tuber ischiadicum) was 26.00 mm. The averagesagittal length and width of the for amenobturatum were 20.00 mm and 14.00 mm, respectively. Sexual differences were observed in the Os coxae. There were three trochanters on the femur while the fovea capitis was absent and replaced by an indistinct depression. The tibia and fibula were almost fused int he distal half before dividing distally to form the medial and lateral malleolus. The tibia has a distal depression not reported in literature. There were 8 tarsal bones and the pedis was complete with five digits (AU)

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