Necroptosis in the developing brain: role in neurodevelopmental disorders.

Cell death is vital to various organismal developmental processes including brain development. Apoptosis, the most recognized programmed cell death, has been linked to several developmental processes and implicated in pruning cells to provide the ultimate tissue integrity. However, more recently, other forms of non-apoptotic programmed cell death have been identified, of which necroptosis is of predominant interest. Necroptosis is a regulated form of necrosis, activated under apoptotic-deficient conditions. Tumour necrosis factor (TNF) is a major activator of necroptosis, and the process is mediated by several kinases including receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like protein (MLKL). Potential roles for necroptosis during brain development have been muted. Necroptosis has been implicated in mediating neurological disorders, and contributing to the severity of these disorders. Here we will review the literature on the role of necroptosis in neurodevelopment, summarizing its molecular mechanisms and highlighting potential implications for disorders of the developing brain.

Modulatory action of Moringa oleifera Lam. on L-arginine induced acute pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is an inflammatory disease of the pancreas with high morbidity and mortality. This study investigates the effect of Moring oleifera (MO) on L-arginine-induced AP in Wistar rats. METHODS: Male Wistar rats were randomly divided into seven groups. Control, AP, Magnesium groups, all fed with standard rat diet, MO leaf groups (5% MLF and 15% MLF), and MO seed groups (5% MSD and 15% MSD) were fed with five or 15% MO leaf or seed supplemented diet for four weeks prior to induction of AP. AP was induced by administration of double doses of L-arginine (320 mg/100 g i.p.) at 1 h interval. All animals were sacrificed 72 h thereafter. RESULTS: Weekly mean feed consumption and body weight were significantly higher in MO groups compared to the control. Amylase level, MDA, MPO, and NO were significantly higher in the AP group than in the control but decreased in Mg and MO groups. While CAT, SOD, GSH, and SH-group were significantly depleted in AP groups, which was attenuated in MO groups. Rats in AP groups showed severe inflammation, necrosis, and edema. These effects were significantly improved in MO groups resulting in lower histological scores compared to the AP group. CONCLUSIONS: Pretreatment with MO could attenuate AP via its antioxidant and anti-inflammatory action.

Cobalt exposure triggers impairments in cognitive and anxiety-like behaviors, brain oxidative stress and inflammation, and hippocampo-amygdala histomorphological alterations: Protective role of aqueous Prosopis africana seed extract.

Objectives: Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments. With a growing interest in the therapeutic roles of herbs, in toxicity research, it's worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt-induced neurotoxicity. Materials and Methods: We treated rats with CoCl2 or CoCl2 in combination with aqueous PA seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments, analysis for oxidative stress, inflammation, and histological and immunohistochemical analysis were performed. Results: Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y-maze tests, and reduced open arm entry and duration in elevated plus-maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2-induced surge in hydrogen peroxide, malondialdehyde, TNF-α and IL-1ß levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced-glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. Conclusion: These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and inflammation.

Methyl Jasmonate: Behavioral and Molecular Implications in Neurological Disorders.

Methyl jasmonate (MJ) is a derivative of the jasmonate family which is found in most tropical regions of the world and present in many fruits and vegetables such as grapevines, tomato, rice, and sugarcane. MJ is a cyclopentanone phytohormone that plays a vital role in defense against stress and pathogens in plants. This has led to its isolation from plants for studies in animals. Many of these studies have been carried out to evaluate its therapeutic effects on behavioral and neurochemical functions. It has however been proposed to have beneficial potential over a wide range of neurological disorders. Hence, this review aims to provide an overview of the neuroprotective properties of MJ and its probable mechanisms of ameliorating neurological disorders. The information used for this review was sourced from research articles and scientific databases using 'methyl jasmonate', 'behavior', 'neuroprotection', 'neurodegenerative diseases', and 'mechanisms' as search words. The review highlights its influences on behavioral patterns of anxiety, aggression, depression, memory, psychotic, and stress. The molecular mechanisms such as modulation of the antioxidant defense, inflammatory biomarkers, neurotransmitter regulation, and neuronal regeneration, underlying its actions in managing neurodegenerative diseases like Alzheimer's and Parkinson's diseases are also discussed. This review, therefore, provides a detailed evaluation of methyl jasmonate as a potential neuroprotective compound with the ability to modify behavioral and molecular biomarkers underlying neurological disorders. Hence, MJ could be modeled as a guided treatment for the management of brain diseases.

New Insights on the Role of Manganese in Alzheimer's Disease and Parkinson's Disease.

Manganese (Mn) is an essential trace element that is naturally found in the environment and is necessary as a cofactor for many enzymes and is important in several physiological processes that support development, growth, and neuronal function. However, overexposure to Mn may induce neurotoxicity and may contribute to the development of Alzheimer's disease (AD) and Parkinson's disease (PD). The present review aims to provide new insights into the involvement of Mn in the etiology of AD and PD. Here, we discuss the critical role of Mn in the etiology of these disorders and provide a summary of the proposed mechanisms underlying Mn-induced neurodegeneration. In addition, we review some new therapy options for AD and PD related to Mn overload.

Caenorhabditis elegans and its applicability to studies on restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological disorder in the United States. This disorder is characterized by an irresistible urge to move the legs, although the symptoms vary in a wide range. The pathobiology of RLS has been linked to iron (Fe) deficiency and dopaminergic (DAergic) dysfunction. Several genetic factors have been reported to increase the risk of RLS. Caenorhabditis elegans (C. elegans) is a well-established animal model with a fully sequenced genome, which is highly conserved with mammals. Given the detailed knowledge of its genomic architecture, ease of genetic manipulation and conserved biosynthetic and metabolic pathways, as well as its small size, ease of maintenance, speedy generation time and large brood size, C. elegans provides numerous advantages in studying RLS-associated gene-environment interactions. Here we will review current knowledge about RLS symptoms, pathology and treatments, and discuss the application of C. elegans in RLS study, including the worm homologous genes and methods that could be performed to advance the pathophysiology RLS.

Effects of Dextromethorphan on Depressive-and Cognitive-Associated Behaviors: A Sexually Dimorphic Study.

INTRODUCTION: We investigated the sexually dimorphic effects of Dextromethorphan (DM) on cognitive and depression-like behaviors as well as on hippocampal histology in rats following acute administration. METHODS: Wistar rats of both sexes were treated with 25 or 50 mg/kg of DM for 7 days via intraperitoneal injection. At the end of the administration, behavioral studies were performed on the Tail Suspension Test (TST) for depressive-like behaviors and the Y-maze for cognitive behaviors. The rats' brains were excised and processed for routine histological analysis. RESULTS: Our results showed that DM significantly increased (P<0.05) immobility time in the TST in male rats but not female ones, and decreased percentage alternation (P<0.001) on the Y-maze in both male and female rats. Histological analysis revealed no morphological changes in the hippocampus following DM treatment. CONCLUSION: DM impairs cognitive functions in both male and female rats without histologic defects in the hippocampus. However, the induced depressive-like behaviors following DM administration may be sexually dependent.

Antimicrobial and Wound Healing Properties of Polyacrylonitrile-Moringa Extract Nanofibers.

A simple and cost-effective material composed of polyacrylonitrile nanofibers containing different concentrations of moringa (MR) leaf extracts was fabricated for antimicrobial properties and wound dressing. The fabricated materials were characterized by scanning electron microscopy, thermal gravimetric analysis, and Fourier transmission infrared spectroscopy. The antibacterial sensitivity of the developed polyacrylonitrile-moringa extract nanofibers was evaluated against Staphylococcus aureus and Escherichia coli by the agar diffusion method. A pronounced antibacterial activity was observed with the increase in the incorporated moringa leaf extract concentration within the polyacrylonitrile-moringa extract nanofibers against the bacterial strains. The best antibacterial sensitivity was observed for nanofibers containing 0.5 g of moringa leaf extract which had an inhibitory zone of 15 mm for E. coli and 12 mm for S. aureus. Furthermore, the cost-effective and biodegradable nanofibrous polyacrylonitrile-moringa extract nanofiber was also used to conduct further studies regarding wound dressing. The result reveals that the increase in the concentrations of moringa leaf extract influenced the healing properties of the material. For days 1, 4, and 7 of the wound dressing experiment, the % wound closure of the rat was the highest for the nanofiber containing 0.5 g of moringa leaf extract (35, 87, and 95%, respectively) compared to the positive control medical gauze (29, 75, and 93%, respectively).

Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain.

Nickel (Ni) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for neurological symptoms in humans. The present study investigated the behavior and histomorphological alterations in brain of rats sub-acutely exposed to nickel chloride (NiCl2) and the possible involvement of oxidative stress. Rats were administered with 5, 10 or 20 mg/kg NiCl2 via intraperitoneal injections for 21 days. Neurobehavioral assessment was performed using the Y-maze and open field test (OFT). Histomorphological analyses of brain tissues, as well as biochemical determination of oxidative stress levels were performed. Results showed that Ni treatments significantly reduced body weight and food intake. Cognitive and motor behaviors on the Y-maze and OFT, respectively, were compromised following Ni treatments. Administration of Ni affected neuronal morphology in the brain and significantly reduced percentage of intact neurons in both hippocampus and striatum. Additionally, markers of oxidative stress levels and nitric oxide (NO) levels were significantly altered following Ni treatments. These data suggest that compromised behavior and brain histomorphology following Ni exposures is associated with increase in oxidative stress.

Chronic nicotine administration does not alter cognitive or mood associated behavioural parameters.

Nicotine, the major specific alkaloid in tobacco smoke, exhibits widespread pharmacological effects and may contribute to deterioration in behaviour. The present study thus examined the effects of its chronic administration on some cognitive and mood associated behaviours. Adult rats weighing between 150 and 200g were randomly divided into 4 groups each of 5 females and 5 males. Three groups were administered graded doses of nicotine at 0.25, 2 and 4mg/kg body weight via subcutaneous injections. One group served as control and received normal saline (vehicle for nicotine). Behavioural tests were performed using the Y-maze, elevated-plus maze (EPM) and tail suspension tests (TST) at various time points. Nicotine produced no significant effect in spontaneous alternation on Y-maze, nor on six parameters scored on EPM (open arm entries, time spent in open arms, time per open arm entries, open/closed arm quotient, closed arm entries, and total arm entries), and also no significant effect on immobility time in TST. This lack of effects was observed to be independent of sex and dose administered. The study shows that nicotine does not produce long-term changes in some cognitive and mood associated behaviours, thus suggesting it could be well tolerated even following chronic administration.

Effects of chronic nicotine administration on body weight, food intake and nitric oxide concentration in female and male rats.

Nicotine is readily consumed through cigarettes; however it is also easily consumed through the various forms of non-prescription nicotine replacement therapy. It has been shown to possess potential therapeutic value for the management of neurologic and neurodegenerative diseases in the last decade. Hence, this study examined the effects of chronic subcutaneous nicotine administration on food intake and body weight as well as on nitric oxide concentrations and total antioxidant capacity in female and male rats. Nicotine was administered to rats via subcutaneous injections at doses of 0.25, 2 and 4mg/kg body weight for 28 days. Control groups received normal saline; the vehicle for nicotine. Food intake by each group was monitored daily and body weight of the animals was measured twice weekly. At the end of drug administration, blood was obtained from each animal via cardiac puncture for biochemical determination of serum total antioxidant capacity (TAC) and nitric (NO) concentrations using standard assay kits. Results show significant loss (p<0.05) of body weight in all nicotine treated female rats. In contrast, male rats showed weight gain, though this was significantly lower (p<0.001) in nicotine treated groups compared to control. Nicotine significantly reduced (p<0.001) food consumed in both female and male rats; however dose related changes were observed in only male rats. No significant difference was observed in TAC following nicotine treatments for both female and male rats. Furthermore, only males exhibited changes in NO concentrations following nicotine treatment, as it significantly increased (p<0.01) NO concentrations in all male treated groups. In conclusion, this study has shown that modulation of body weight, food consumption and nitric oxide formation by nicotine is sexually dimorphic. Also, the study suggests that nicotine modulation of food intake and body weight and its modulation of NO may be independent of each other.