Brain Sciences — Open Access Journal of Neuroscience

Alzheimer’s disease (AD) is characterized by the accumulation of neurofibrillary tangles (NFT), deposition of beta amyloid plaques, and consequent neuronal loss in the brain tissue. Oxidative stress to the neurons is often attributed to AD, but its link to NFT and β-amyloid protein (BAP) still remains unclear. In an animal model of AD, we boosted the oxidative defense by N-Acetyl cysteine (NAC), a precursor of glutathione, a powerful antioxidant and free radical scavenger, to understand the link between oxidative stress and NFT. In mimicking AD, intracerebroventricular (ICV) colchicine, a microtubule disrupting agent also known to cause oxidative stress was administered to the rats. The animal groups consisted of an age-matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in a passive avoidance test; neuronal degeneration was quantified using Nissl staining. NFT in the form of abnormal tau expression in different regions of the brain were evaluated through immunohistochemistry using rabbit anti-tau antibody. ICV has resulted in significant cognitive and neuronal loss in medial prefrontal cortex (MFC) and all the regions of the hippocampus. It has also resulted in increased accumulation of intraneuronal tau in the hippocampus and MFC. NAC treatment in AD model rats has reversed the cognitive loss and neuronal degeneration. The intraneuronal tau expression also minimized with NAC treatment in AD model rats. Thus, our findings suggest that an antioxidant supplement during the progression of AD is likely to prevent neuronal degeneration by minimizing the neurofibrillary degeneration in the form of tau accumulation. Full article

Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation. Full article

Background: Gender may alter African Americans’ vulnerability to discrimination. The type of outcomes that follow exposure to discrimination may also be gender-specific. Although teacher discrimination is known to deteriorate school performance, it is yet unknown whether male and female African American youth differ in the effect of teacher discrimination on school performance. Objective: This cross-sectional study explored the moderating role of gender on the effect of teacher discrimination on school performance in a national sample of African American youth. Methods: The National Survey of American Life-Adolescent Supplement (NSAL-A) enrolled a nationally representative sample (n = 810) of 13–17-year-old African American youth. Demographic factors, socioeconomic status, teacher discrimination, and school performance (grade point average, GPA) were measured. Linear multivariable regression models were applied for data analysis. Results: Males and females reported similar levels of perceived teacher discrimination. In the pooled sample, higher teacher discrimination was associated with lower school performance among African American youth (b = −0.35; 95% confidence interval (CI) = −0.49 to −0.22). Gender interacted with perceived teacher discrimination (b = 12; 95% CI = 0.24–2.02), suggesting a significant difference between males and females in the magnitude of the association between perceived teacher discrimination and GPA. In stratified models, perceived teacher discrimination was associated with worse school performance of females (b = −12; 95% CI = −0.03 to −2.78) but not males (b = 0.01; 95% CI = −0.07 to 0.08). Conclusion: In line with previous studies, gender was found to alter the vulnerability of African American youth to perceived discrimination. African American boys and girls may differ in their sensitivity to the effects of teacher discrimination on school performance. Full article

Background: Recent research has shown smaller health effects of socioeconomic status (SES) indicators such as education attainment for African Americans as compared to whites. However, less is known about diminished returns based on gender within African Americans. Aim: To test whether among African American men are at a relative disadvantage compared to women in terms of having improved mental health as a result of their education attainment. This study thus explored gender differences in the association between education attainment and mental health, using a representative sample of American adults. Methods: The National Survey of American Life (NSAL; 2003) recruited 3570 African American adults (2299 females and 1271 males). The dependent variables were depressive symptoms and psychological distress. The independent variable was education attainment. Race was the focal moderator. Age, employment status, and marital status were covariates. Linear regressions were used for data analysis. Results: In the pooled sample that included both male and female African American adults, high education attainment was associated with lower depressive symptoms and psychological distress, net of covariates. Significant interactions were found between gender and education attainment with effects on depressive symptoms and psychological distress, suggesting stronger protective effects of high education attainment against depressive symptoms and psychological distress for female as compared to male African Americans. Conclusion: A smaller gain in mental health with respect to educational attainment for male African American males as compared to African American females is in line with studies showing high risk of depression in African American men of high-socioeconomic status. High-SES African American men need screening for depression and psychological distress. Full article

In literature nothing is known about the clinical significance of Ultra High Risk (UHR) symptoms in children and adolescents with diagnosis of obsessive–compulsive disorder (OCD). In this study, we examined the prevalence of UHR symptoms and their relationship with severity of obsessive–compulsive symptomatology, global, social, and role functioning, and level of associated depressive symptoms in a clinical sample (n = 51) of children and adolescents aged between 8 and 17 years with a diagnosis of OCD. The prevalence of UHR symptoms in this sample was 43.1%. We divided the whole sample into two groups: children and adolescents with OCD and UHR symptoms (n = 22) and children and adolescents with OCD without UHR symptoms (n = 29). Our findings suggest that the group with OCD and UHR symptoms shows worse global, social, and role functioning than the group with OCD without UHR symptoms. No differences were found on the severity of obsessive–compulsive symptomatology, the number of psychiatric diagnoses associated, and the level of depressive symptoms. The presence of UHR symptoms in children and adolescents with OCD could cause significant functional impairment and should be considered in order to plan specific and targeted therapeutic interventions. Full article

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes. Full article

Recent work found that experimental pain appeared to negate alterations in cortical somatosensory evoked potentials (SEPs) that occurred in response to motor learning acquisition of a novel tracing task. The goal of this experiment was to further investigate the interactive effects of pain stimulus location on motor learning acquisition, retention, and sensorimotor processing. Three groups of twelve participants (n = 36) were randomly assigned to either a local capsaicin group, remote capsaicin group or contralateral capsaicin group. SEPs were collected at baseline, post-application of capsaicin cream, and following a motor learning task. Participants performed a motor tracing acquisition task followed by a pain-free retention task 24–48 h later while accuracy data was recorded. The P25 (p < 0.001) SEP peak significantly decreased following capsaicin application for all groups. Following motor learning acquisition, the N18 SEP peak decreased for the remote capsaicin group (p = 0.02) while the N30 (p = 0.002) SEP peaks increased significantly following motor learning acquisition for all groups. The local, remote and contralateral capsaicin groups improved in accuracy following motor learning (p < 0.001) with no significant differences between the groups. Early SEP alterations are markers of the neuroplasticity that accompanies acute pain and motor learning acquisition. Improved motor learning while in acute pain may be due to an increase in arousal, as opposed to increased attention to the limb performing the task. Full article

Regeneration refers to regrowth of tissue in the central nervous system. It includes generation of new neurons, glia, myelin, and synapses, as well as the regaining of essential functions: sensory, motor, emotional and cognitive abilities. Unfortunately, regeneration within the nervous system is very slow compared to other body systems. This relative slowness is attributed to increased vulnerability to irreversible cellular insults and the loss of function due to the very long lifespan of neurons, the stretch of cells and cytoplasm over several dozens of inches throughout the body, insufficiency of the tissue-level waste removal system, and minimal neural cell proliferation/self-renewal capacity. In this context, the current review summarized the most common features of major neurodegenerative disorders; their causes and consequences and proposed novel therapeutic approaches. Full article

Background: Minorities’ Diminished Return (MDR) can be defined as smaller health gains from socioeconomic status (SES) indicators, such as education attainment among ethnic minorities compared to the majority group. The current study tested whether income explains why Black and White adults differ in the association between education attainment and self-rated health (SRH). Methods: With a cross-sectional design, this study used data from Cycle 5 of the Health Information National Trends Survey (HINTS), 2017. With a nationally representative sample, the HINTS study generates results that are generalizable to US adults. This study included 2277 adults who were either non-Hispanic White (n = 1868; 82%) or non-Hispanic Black (n = 409; 18%). The independent variable was education attainment. The dependent variable was SRH, measured using a standard single item. Age, gender, and health insurance status were covariates. Ethnicity was the focal moderator. Income was the mediator. A structural equation model (SEM) was applied for data analysis. Results: Overall, higher education attainment was associated with better SRH, net of covariates. However, a significant interaction between ethnicity and education attainment suggested a smaller SRH gain from education for Blacks compared to Whites. This interaction could be explained by Black–White differences in income. Conclusion: Our study results suggests that labor market preferences may explain smaller effects of education attainment on SRH for Blacks relative to Whites. Given this finding and other studies documenting MDR, policies should reduce labor market discrimination, increasing job opportunities and reducing the racial pay gap for Blacks. Programs should help Blacks compete for prestigious and high-paying jobs. Full article

Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann’s area 9 of the prefrontal cortex (PFC). Brain samples from 44 individuals were divided into equal groups of 11 control, 11 alcoholic, 11 non-alcoholic suicides, and 11 suicide alcoholics matched for age, sex, and post-mortem delay. Tissue from alcoholic cohorts displayed significantly reduced expression of α- and β-tubulins, and increased levels of acetylated α-tubulin. Protein levels of histone deacetylase-6 (HDAC6), and the microtubule-associated proteins MAP-2 and MAP-tau were reduced in alcoholic cohorts, although for MAPs this was not significant. Tubulin gene expressions increased in alcoholic cohorts but not significantly. Brains from rats administered alcohol for 4 weeks also displayed significantly reduced tubulin protein levels and increased α-tubulin acetylation. PFC tissue from control subjects had reduced tubulin protein expression that was most notable from the sixth to the eighth decade of life. Collectively, loss of neuronal tubulin proteins are a hallmark of both chronic alcohol consumption and natural brain ageing. The reduction of cytosolic tubulin proteins could contribute to the brain volumetric losses reported for alcoholic patients and the elderly. Full article

Even though obese individuals often succeed with weight loss, long-term weight loss maintenance remains elusive. Dietary, lifestyle and psychosocial correlates of weight loss maintenance have been researched, yet the nature of maintenance is still poorly understood. Studying the neural processing of weight loss maintainers may provide a much-needed insight towards sustained obesity management. In this narrative review, we evaluate and critically discuss available evidence regarding the food-related neural responses of weight loss maintainers, as opposed to those of obese or lean persons. While research is still ongoing, available data indicate that following weight loss, maintainers exhibit persistent reward related feeling over food, similar to that of obese persons. However, unlike in obese persons, in maintainers, reward-related brain activity appears to be counteracted by subsequently heightened inhibition. These findings suggest that post-dieting, maintainers acquire a certain level of cognitive control which possibly protects them from weight regaining. The prefrontal cortex, as well as the limbic system, encompass key regions of interest for weight loss maintenance, and their contributions to long term successful weight loss should be further explored. Future possibilities and supportive theories are discussed. Full article

A comprehensive review of the literature-to-date on functional magnetic resonance imaging (fMRI) of the spinal cord is presented. Spinal fMRI has been shown, over more than two decades of work, to be a reliable tool for detecting neural activity. We discuss 10 key points regarding the history, development, methods, and applications of spinal fMRI. Animal models have served a key purpose for the development of spinal fMRI protocols and for experimental spinal cord injury studies. Applications of spinal fMRI span from animal models across healthy and patient populations in humans using both task-based and resting-state paradigms. The literature also demonstrates clear trends in study design and acquisition methods, as the majority of studies follow a task-based, block design paradigm, and utilize variations of single-shot fast spin-echo imaging methods. We, therefore, discuss the similarities and differences of these to resting-state fMRI and gradient-echo EPI protocols. Although it is newly emerging, complex connectivity and network analysis is not only possible, but has also been shown to be reliable and reproducible in the spinal cord for both task-based and resting-state studies. Despite the technical challenges associated with spinal fMRI, this review identifies reliable solutions that have been developed to overcome these challenges. Full article

Reading is essentially a two-channel function, requiring the integration of intact visual and auditory processes both peripheral and central. It is essential for normal reading that these component processes go forward automatically. Based on this model, Boder described three main subtypes of dyslexia: dysphonetic dyslexia (DD), dyseidetic, mixed and besides a fourth group defined non-specific reading delay (NSRD). The subtypes are identified by an algorithm that considers the reading quotient and the % of errors in the spelling test. Chiarenza and Bindelli have developed the Direct Test of Reading and Spelling (DTRS), a computerized, modified and validated version to the Italian language of the Boder test. The sample consisted of 169 subjects with DD and 36 children with NSRD. The diagnosis of dyslexia was made according to the DSM-V criteria. The DTRS was used to identify the dyslexia subtypes and the NSRD group. 2–5 min of artefact-free EEG (electroencephalogram), recorded at rest with eyes closed, according to 10–20 system were analyzed. Stability based Biomarkers identification methodology was applied to the DTRS and the quantitative EEG (QEEG). The reading quotients and the errors of the reading and spelling test were significantly different in the two groups. The DD group had significantly higher activity in delta and theta bands compared to NSRD group in the frontal, central and parietal areas bilaterally. The classification equation for the QEEG, both at the scalp and the sources levels, obtained an area under the robust Receiver Operating Curve (ROC) of 0.73. However, we obtained a discrimination equation for the DTRS items which did not participate in the Boder classification algorithm, with a specificity and sensitivity of 0.94 to discriminate DD from NSRD. These results demonstrate for the first time the existence of different neuropsychological and neurophysiological patterns between children with DD and children with NSRD. They may also provide clinicians and therapists warning signals deriving from the anamnesis and the results of the DTRS that should lead to an earlier diagnosis of reading delay, which is usually very late diagnosed and therefore, untreated until the secondary school level. Full article

Literature on children with Klinefelter Syndrome (KS) points to general linguistic difficulties in both comprehension and production among other cognitive functions, and in the majority of cases, these coexist with an intellectual level within the norms. In these conditions, children having language delay generally engage in language therapy and are systematically monitored across ages. In this article, we present the profiles of two children with KS (47, XXY), aged 9.1 (Child S) and 13 (Child D), whose language development was assessed as adequate at age 3, and for this reason, did not receive any language treatment. At the present stage, their IQ, as measured by Wechsler Scales (Child S: 92; Child D: 101), is within the norm, but they both present marked weaknesses in pragmatic skills such as figurative language comprehension. The analysis of these two cases points to the need to go beyond global indexes of verbal abilities, as the same global index may mask a wide diversification of individual profiles. In addition, this study underlines the importance of monitoring the developmental trajectories of children like Child D and Child S, because weaknesses in pragmatic skills that are relevant for both academic achievement and social adaptation could emerge at later stages. Full article

Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses. Full article

Musical aptitude and language talent are highly intertwined when it comes to phonetic language ability. Research on pre-school children’s musical abilities and foreign language abilities are rare but give further insights into the relationship between language and musical aptitude. We tested pre-school children’s abilities to imitate unknown languages, to remember strings of digits, to sing, to discriminate musical statements and their intrinsic (spontaneous) singing behavior (“singing-lovers versus singing nerds”). The findings revealed that having an ear for music is linked to phonetic language abilities. The results of this investigation show that a working memory capacity and phonetic aptitude are linked to high musical perception and production ability already at around the age of 5. This suggests that music and (foreign) language learning capacity may be linked from childhood on. Furthermore, the findings put emphasis on the possibility that early developed abilities may be responsible for individual differences in both linguistic and musical performances. Full article

Background: Past studies have evaluated the association of various comorbidities with bipolar disorder. This study analyzes differences in the prevalence and association of medical and psychiatric comorbidities in bipolar patients by gender. Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). Using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study population to comprise those with a primary diagnosis of bipolar disorder and then obtained information about comorbidities. The differences in comorbidities by gender were quantified using chi-square tests and the logistic regression model (odds ratio (OR)). Results: Hypertension (20.5%), asthma (12.5%) and hypothyroidism (8.1%) were the top medical comorbidities found in bipolar patients. Migraine and hypothyroidism were seen three times higher in females (OR = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn’s disease (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR = 1.663) compared to males. Conclusion: Women with bipolar disorder have a much higher medical comorbidity burden than men and may highly benefit from an integrated team of physicians to manage their condition and improve their health-related quality of life. Full article

We searched for drugs that alleviate the reduction of dopaminergic neurons caused by the administration of lipopolysaccharide (LPS) to the substantia nigra of the rat brain. Human milk fat globule-EGF factor 8 protein (MFG-E8) is similar to MFG-E8-S, a short isoform, of the mouse MFG-E8. However, the function of MFG-E8-S was not clear. Rats with LPS-induced Parkinson’s disease were prepared and the effects of human MFG-E8 were examined. MFG-E8 improved the significant reduction in mesencephalic dopamine neurons induced by the administration of LPS. LPS was administered to human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons to induce inflammation and the effect of MFG-E8 was examined. MFG-E8 showed no toxicity toward neurons. We reanalyzed the results using public microarray data. MFG-E8 mRNA was found to be expressed in all parts of the body, particularly by adipose-derived stem cells (ADSCs). Furthermore, we investigated the culture supernatant of ADSCs using the liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis method and successfully identified the peptide of the MFG-E8 F5/8 type C domain. The results suggested that MFG-E8-S may have a preventive effect against Parkinson’s disease. Full article