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.

Permanent Tooth Eruption Patterns in Nigerian Local Pigs.

Pigs are diphyodonts with heterodont dentition and have been used in studies involving teeth and jawbone regeneration, and dental implants. Patterns of tooth eruption are used to age animals and determine the effects of environmental and genetic influences on occurrence of variations. As with other species, variations exist in the tooth eruption pattern in pigs. The aim of this study was to determine the permanent teeth eruption patterns of Nigerian local pigs. Twenty-six healthy pigs were observed throughout the study period. Pigs were firmly held in dorsal or lateral recumbency and their mouths gently held open to visually examine all quadrants of the dental arches (right and left maxillary, right and left mandibular). Observations were recorded from 16 weeks of age, until the last permanent tooth erupted. Results obtained from the study showed that males had lower mean values for eruption time (54%) of examined teeth in comparison to females. The mean values of eruption time for the maxillary third incisor, the mandibular and maxillary canines, and the mandibular fourth premolar teeth were statistically significant in the males (P = .0017, P = .0088, P = .0002 and P = .0244, respectively). Sixty-nine percent of the adult pigs did not have eruption of the mandibular first premolar, while polydontia was observed in the maxillary and mandibular incisors. These results show that intra-breed and inter-breed variations exist in the dental eruption pattern in pigs. The data obtained from this study can be used for comparative dental studies and can aid further research on the developmental anatomy of Nigerian local pigs.

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.

An alternate prospect in detecting presymptomatic and asymptomatic COVID-19 carriers through odor differentiation by HeroRATs.

The need for a cheap, ubiquitous, sensitive, rapid, noninvasive means of screening large numbers of presymptomatic and asymptomatic samples at departure or arrival into ports of countries, high-risk areas, and within communities forms the subject of this review. The widely used diagnostic test for the SARS-CoV 2 is the real-time reverse transcription-polymerase chain reaction assay while antibody-based techniques are being introduced as supplemental tools, but the lack of specialized nucleic acid extraction and amplification laboratories hampers/slows down timely large-scale testing. The use of animals with sensitive olfactory cue as an alternate testing model could serve as an alternative to detect COVID-19 in the saliva of carriers. The African giant rats are highly versatile and detect odorant molecules from carriers of pathogens with high percentage success after few months of training, hence can be taught to detect odor differences of COVID-19 in asymptomatic and presymptomatic individuals. If these are trained, they could help to curtail further spread of COVID infections.

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.

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.

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.