Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice.

Alcohol abuse by adolescents is becoming a serious health concern as they often progress to becoming alcoholics later in life which may lead to heart problems. Chronic alcohol use alters the cardiac function and structure, such as haemodynamic changes, weakening and loss of cardiomyocytes, myocardial fibrosis, and inflammation. Simvastatin is a commonly used drug for the treatment and management of various cardiovascular problems but information on its protective effects against alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation is lacking in the literature. Four-week-old male (n = 5) and female (n = 5) C57BL/6 J mice were assigned to each experimental group: (I) NT-no administration of alcohol or Simvastatin; (II) ALC-2.5 g/Kg/day of 20% alcohol via intraperitoneal injection (i.p.); (III) SIM-5 mg/Kg/day of Simvastatin via oral gavage; (iv) ALC + SIM5-5 mg/Kg/day of Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p.; and (v) ALC + SIM15-15 mg/Kg/day Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p. After the 28-day treatment period, the heart was removed and processed for H&E, Masson's trichrome, or TNF-α immunolabelling. The area and diameter of cardiomyocytes were measured on the H&E-stained sections. The distribution of collagen or TNF-α expression was quantified using the deconvolution tool of ImageJ software. The results confirmed alcohol-induced toxicity on the cardiomyocytes and Simvastatin reduced alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation in both sexes. This study demonstrated that Simvastatin, an FDA approved and easily accessible drug, may be beneficial in lowering the prevalence of alcohol-induced cardiovascular diseases (especially in adolescents) which will have a huge financial implication on health systems worldwide.

Machine learning and discriminant function analysis in the formulation of generic models for sex prediction using patella measurements.

Sex prediction from bone measurements that display sexual dimorphism is one of the most important aspects of forensic anthropology. Some bones like the skull and pelvis display distinct morphological traits that are based on shape. These morphological traits which are sexually dimorphic across different population groups have been shown to provide an acceptably high degree of accuracy in the prediction of sex. A sample of 100 patella of Mixed Ancestry South Africans (MASA) was collected from the Dart collection. Six parameters: maximum height (maxh), maximum breadth (maxw), maximum thickness (maxt), the height of articular facet (haf), lateral articular facet breadth (lafb), and medial articular facet breath (mafb) were used in this study. Stepwise and direct discriminant function analyses were performed for measurements that exhibited significant differences between male and female mean measurements, and the "leave-one-out" approach was used for validation. Moreover, we have used eight classical machine learning techniques along with feature ranking techniques to identify the best feature combinations for sex prediction. A stacking machine learning technique was trained and validated to classify the sex of the subject. Here, we have used the top performing three ML classifiers as base learners and the predictions of these models were used as inputs to different machine learning classifiers as meta learners to make the final decision. The measurements of the patella of South Africans are sexually dimorphic and this observation is consistent with previous studies on the patella of different countries. The range of average accuracies obtained for pooled multivariate discriminant function equations is 81.9-84.2%, while the stacking ML technique provides 90.8% accuracy which compares well with those presented for previous studies in other parts of the world. In conclusion, the models proposed in this study from measurements of the patella of different population groups in South Africa are useful resent with reasonably high average accuracies.

Neural stem cell research in Africa: current realities and future prospects.

Neural stem cells (NSCs) are immature progenitor cells that are found in developing and adult brains that have the potential of dividing actively and renewing themselves, with a complex form of gene expression. The generation of new brain cells in adult individuals was initially considered impossible, however, the landmark discovery of human neural stem cells in the hippocampus has been followed by further discoveries in other discreet regions of the brain. Investigation into the current state in Africa of the research and use of NSCs shows relatively limited activities on the continent. Information on the African application of NSCs for modelling disease mechanisms, drug discovery, and therapeutics is still limited. The International Brain Research Organization (IBRO)-African Regional Committee (ARC), with support from the Company of Biologists, and the Movement Disorder Society, sponsored the first African Basic School on NSC in Ibadan, Nigeria, with the vision of bringing together young neuroscientists and physicians across different fields in neuroscience to learn from leaders who have applied NSCs in stem cell research, the pathophysiology of neurodegenerative diseases, neuroanatomy, and neurotherapeutics. Twenty early-career researchers in academic institutions at junior and senior faculty cadres were selected from South Africa, Uganda and Nigeria. The students and organizer of the school, who wrote this review on the state of NSCs research in Africa, recommended the following: (1) other African countries can take a cue from South Africa and Nigeria in probing the phenomena of adult neurogenesis in unique animal species on the continent; (2) Africa should leverage the expertise and facilities of South African scientists and international collaborators in scaling up NSC research into these unique species and (3) Centers of Excellence should be established on the continent to serve as research hubs for training postgraduate students, and facilities for African scientists who trained overseas on NSCs.

Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis.

Neurogenesis in the subgranular zone (SGZ) of the adult hippocampus can be stimulated by a variety of means, including via exposure of experimental animals to an enriched environment that provides additional sensory, social, and motor stimulation. Tangible health and cognitive benefits accrue in enriched animals, including the amelioration of signs modelling psychiatric, neurological and neurodegenerative conditions that affect humans, which may in part be due to enhanced production of neurons. A key factor in the neuronal response to enrichment is the release of brain-derived neurotrophic factor (BDNF) and the activation of the Mitogen-Activated Protein Kinase (MAPK) cascade, which can lead to the stimulation of neurogenesis. Mitogen- and Stress-Activated protein Kinase 1 (MSK1) is a nuclear enzyme downstream of BDNF and MAPK that regulates transcription. MSK1 has previously been implicated in both basal and stimulated neurogenesis on the basis of studies with mice lacking MSK1 protein. In the present study, using mice in which only the kinase activity of MSK1 is lacking, we show that the rate of cellular proliferation in the SGZ (Ki-67 staining) is unaffected by the MSK1 kinase-dead (KD) mutation, and no different from controls levels after five weeks of enrichment. However, compared to wild-type mice, the number of doublecortin (DCX)-positive cells was greater in both standard-housed and enriched MSK1 KD mice. These observations suggest that, while MSK1 does not influence the basal rate of proliferation of neuronal precursors, MSK1 negatively regulates the number of cells destined to become neurons, potentially as a homeostatic control on the number of new neurons integrating into the dentate gyrus.

Women and substance use disorders in low- and middle-income countries: A call for advancing research equity in prevention and treatment.

Although the prevalence of substance use disorders (SUDs) is higher among men, women with SUDs in low- and middle-income countries (LMICs) face unique challenges. Poverty and adversity, inequality of women, and disparities in access to treatment and prevention services exacerbate biological, psychological and social correlates of substance use disorders for women living in low-resource settings. Increasing the inclusion of women in research has long been a goal, though even high income countries struggle to achieve parity. In LMICs, women with SUDs are often neglected from global research due to underreporting and the disproportionate focus of global substance use research on men. We will discuss risk factors for SUDs that are particularly relevant for women residing in LMICs in order to gain insight into neglected areas of research and opportunities for prevention and treatment.

Changes to the somatosensory barrel cortex in C57BL/6J mice at early adulthood (56 days post-natal) following prenatal alcohol exposure.

Children with Fetal Alcohol Spectrum Disorder (FASD) have impaired sensory processing skills as a result of neurodevelopmental anomalies. The somatosensory barrel field of rodent brain is a readily accessible model for studying the effects of alcohol exposure. Within the barrel field, the posterior medial barrel subfield (PMBSF) receives sensory inputs from the large vibrissae on the contralateral face. This study reports on the consequence of prenatal exposure to alcohol on the somatosensory cortices of mice later in life. Two control groups, a sucrose and a non-treated control, were also examined. At postnatal day (PND) 56 the cerebral hemisphere of mice from each group were processed for cytochrome oxidase reactivity. In contrast to previous studies, there were no significant differences in the mean areas of: (I) the PMBSF enclosure, (II) the PMBSF barrels, (III) the individual PMBSF barrels and (IV) the septal portion of the PMBSF in the alcohol group compared to the controls. However barrel sizes in rows D and E in the alcohol group were significantly reduced, indicating an alcohol-induced damage on the barrel development and which may reduce the amount of the cortex devoted to processing somatosensory input- a common defect seen in children with FASD.

Hippocampal neurogenesis in the C57BL/6J mice at early adulthood following prenatal alcohol exposure.

We examined the effect of chronic prenatal alcohol exposure (PAE) on the process of adult neurogenesis in C57BL/6J mice at early adulthood (PND 56). Pregnant mice, and their in utero litters, were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentrations averaging 184 mg/dL (CA group). Two control groups, sucrose (CAc) and non-treated (NTc) control groups were also examined. The brains of pups at PND 56 from each experimental group were sectioned in a sagittal plane, and stained for Nissl substance with cresyl violet, and immunostained for Ki-67 which labels proliferative cells and doublecortin (DCX) for immature neurons. Morphologically, the neurogenic pattern was identical in all three groups studied. Populations of Ki-67 immunopositive cells in the dentate gyrus were not statistically significantly different between the experimental groups and there were no differences between the sexes. Thus, the PAE in this study does not appear to have a strong effect on the proliferative process in the adult hippocampus. In contrast, the numbers of immature neurons, labeled with DCX, was statistically significantly lower in the prenatal alcohol exposed mice compared with the two control groups. Alcohol significantly lowered the number of DCX hippocampal cells in the male mice, but not in the female mice. This indicates that the PAE appears to lower the rate of conversion of proliferative cells to immature neurons and this effect of alcohol is sexually dimorphic. This lowered number of immature neurons in the hippocampus appears to mirror hippocampal dysfunctions observed in FASD children.

Changes in the Cholinergic, Catecholaminergic, Orexinergic and Serotonergic Structures Forming Part of the Sleep Systems of Adult Mice Exposed to Intrauterine Alcohol.

We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentration (BAC)s averaging 1.84 mg/ml (chronic alcohol group, CA). Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc) and a non-treated control group (NTc), were also examined. At 56 days post-natal, the pups from each group were sacrificed and the whole brain sectioned in a coronal plane and immunolabeled for cholineacetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5HT) and orexin-A (OxA) which labels cholinergic, catecholaminergic, serotonergic and orexinergic structures respectively. The overall nuclear organization and neuronal morphology were identical in all three groups studied, and resemble that previously reported for laboratory rodents. Quantification of the estimated numbers of ChAT immunopositive (+) neurons of the pons, the TH+ neurons of the pons and the OxA+ neurons of the hypothalamus showed no statistically significant difference between the three experimental groups. The stereologically estimated areas and volumes of OxA+ neurons in the CA group were statistically significantly larger than the groups not exposed to prenatal alcohol, but the ChAT+ neurons in the CA group were statistically significantly smaller. The density of orexinergic boutons in the anterior cingulate cortex was lower in the CA group than the other groups. No statistically significant difference was found in the area and volume of TH+ neurons between the three experimental groups. These differences are discussed in relation to the sleep disorders recorded in children with fetal alcohol spectrum disorder (FASD).