Canine degenerative myelopathy (DM) is a progressive neurological disorder that may be considered to be a large animal model for specific forms of the fatal human disease, familial amyotrophic lateral sclerosis (fALS). DM is associated with a c118G>A mutation of the superoxide dismutase 1 (Sod1) gene, and a significant proportion of cases are inherited in an autosomal recessive manner in contrast to the largely, but not exclusively, dominant mode of inheritance in fALS. The consensus view is that these Sod1/SOD1 mutations result in a toxic gain of function but the mechanisms remain unclear. Here we used an in vitro neuroblastoma cell line transfection system to monitor wild-type and mutant forms of SOD1 fusion proteins containing either a Cherry or an enhanced green fluorescent protein (EGFP) tag. These fusion proteins retained SOD1 enzymatic activity on a native gel assay system. We demonstrate that SOD1 aggregate density is significantly higher in DM transfectants compared to wild-type. In addition, we show by co-immunoprecipitation and confocal microscopy, evidence for a potential interaction between wild-type and mutant forms of SOD1 in co-transfected cells. While in vitro studies have shown SOD1 heterodimer formation in fALS models, this is the first report for DM SOD1. Therefore, despite for the majority of cases there is a difference in the mode of inheritance between fALS and DM, a similar interaction between wild-type and mutant SOD1 forms can occur. Clarifying the role of SOD1 in DM may also be of benefit to understanding the role of SOD1 in fALS.
Brain-derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aβ)-associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aβ1-40-induced retinal and optic nerve injury. In this study, exposure to Aβ1-40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF-treated group compared with Aβ1-40 group. H&E-stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aβ1-40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF-treated animals. After Aβ1-40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF-treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aβ was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF-treated than in Aβ1-40-treated rats. Both visual object recognition tests using an open-field arena and a Morris water maze showed that BDNF improved rats' ability to recognise visual cues (objects with different shapes) after Aβ1-40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aβ1-40-induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.
Epilepsy is one of the oldest known neurological disorders and is characterized by recurrent seizure activity. It has a high incidence rate, affecting a broad demographic in both developed and developing countries. Comorbid conditions are frequent in patients with epilepsy and have detrimental effects on their quality of life. Current management options for epilepsy include the use of anti-epileptic drugs, surgery, or a ketogenic diet. However, more than 30% of patients diagnosed with epilepsy exhibit drug resistance to anti-epileptic drugs. Further, surgery and ketogenic diets do little to alleviate the symptoms of patients with pharmacoresistant epilepsy. Thus, there is an urgent need to understand the underlying mechanisms of pharmacoresistant epilepsy to design newer and more effective anti-epileptic drugs. Several theories of pharmacoresistant epilepsy have been suggested over the years, the most common being the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis. In our review, we discuss the main theories of pharmacoresistant epilepsy and highlight a possible interconnection between their mechanisms that could lead to the development of novel therapies for pharmacoresistant epilepsy.
Seeing a face being touched in spatial and temporal synchrony with the own face produces a bias in self-recognition, whereby the other face becomes more likely to be perceived as the self. The present study employed event-related potentials to explore whether this enfacement effect reflects initial face encoding, enhanced distinctiveness of the enfaced face, modified self-identity representations, or even later processing stages that are associated with the emotional processing of faces. Participants were stroked in synchrony or asynchrony with an unfamiliar face they observed on a monitor in front of them, in a situation approximating a mirror image. Subsequently, event-related potentials were recorded during the presentation of (a) a previously synchronously stimulated face, (b) an asynchronously stimulated face, (c) observers' own face, (d) filler faces, and (e) a to-be-detected target face, which required a response. Observers reported a consistent enfacement illusion after synchronous stimulation. Importantly, the synchronously stimulated face elicited more prominent N170 and P200 responses than the asynchronously stimulated face. By contrast, similar N250 and P300 responses were observed in these conditions. These results suggest that enfacement modulates early neural correlates of face encoding and facial prototypicality, rather than identity self-representations and associated emotional processes.
Of the 572 neuroscience-related studies published in Nigerian from 1996 to 2017, <5% used state-of-the-art techniques, none used transgenic models, and only one study was published in a top-tier journal.
Candida spp., Malassezia spp., Cladosporium spp. and Alternaria spp. are among the most common fungi detected in the brain of patients with Alzheimer's disease (AD). These fungi are opportunistic organisms, where they often cause infection among immunocompromised patients. Coincidentally, these fungi can reach the brain and cause fungal meningitis. In general, they enter the brain via systemic infection due to disrupted epithelial barrier from skin and gut colonization. Once it reaches the brain, Candida species has been postulated to induce fungal glial granulomas with amyloid precursor protein (APP) accumulated inside. Cleavage of APP can lead to the production of amyloid beta (Aβ). Malassezia species can lead to neuroinflammation via activating helper T-cell (Th) 1 and Th17 immune response. Besides that, the pathogenesis of Cladosporium species and Alternaria species in AD remains unknown, but it could be related to the neuroinflammation. These two fungal species may have involved in acetylcholinesterase (AChE) inhibitor production in the brain. All these four fungi can be detected at the same time in the brain, which contribute to chronic neuroinflammation and neurodegeneration in the brain. This review hopes to shed some light in understanding the presence of fungi in the brain and their possible role in AD pathogenesis.