Algebra dissociates from arithmetic in the brain semantic network

Background Mathematical expressions mainly include arithmetic (such as 8 − (1 + 3)) and algebra (such as a − (b + c)). Previous studies have shown that both algebraic processing and arithmetic involved the bilateral parietal brain regions. Although previous studies have revealed that algebra was dissociated from arithmetic, the neural bases of the dissociation between algebraic processing and arithmetic is still unclear. The present study uses functional magnetic resonance imaging (fMRI) to identify the specific brain networks for algebraic and arithmetic processing. Methods Using fMRI, this study scanned 30 undergraduates and directly compared the brain activation during algebra and arithmetic. Brain activations, single-trial (item-wise) interindividual correlation and mean-trial interindividual correlation related to algebra processing were compared with those related to arithmetic. The functional connectivity was analyzed by a seed-based region of interest (ROI)-to-ROI analysis. Results Brain activation analyses showed that algebra elicited greater activation in the angular gyrus and arithmetic elicited greater activation in the bilateral supplementary motor area, left insula, and left inferior parietal lobule. Interindividual single-trial brain-behavior correlation revealed significant brain-behavior correlations in the semantic network, including the middle temporal gyri, inferior frontal gyri, dorsomedial prefrontal cortices, and left angular gyrus, for algebra. For arithmetic, the significant brain-behavior correlations were located in the phonological network, including the precentral gyrus and supplementary motor area, and in the visuospatial network, including the bilateral superior parietal lobules. For algebra, significant positive functional connectivity was observed between the visuospatial network and semantic network, whereas for arithmetic, significant positive functional connectivity was observed only between the visuospatial network and phonological network. Conclusion These findings suggest that algebra relies on the semantic network and conversely, arithmetic relies on the phonological and visuospatial networks.

NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice

Background Brain aging is an important risk factor in many human diseases, such as Alzheimer’s disease (AD). The production of excess reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and the maturation of inflammatory cytokines caused by activation of the NOD-like receptor protein 1 (NLRP1) inflammasome play central roles in promoting brain aging. However, it is still unclear when and how the neuroinflammation appears in the brain during aging process. Methods In this study, we observed the alterations of learning and memory impairments, neuronal damage, NLRP1 inflammasome activation, ROS production and NOX2 expression in the young 6-month-old (6 M) mice, presenile 16 M mice, and older 20 M and 24 M mice. Results The results indicated that, compared to 6 M mice, the locomotor activity, learning and memory abilities were slightly decreased in 16 M mice, and were significantly decreased in 20 M and 24 M mice, especially in the 24 M mice. The pathological results also showed that there were no significant neuronal damages in 6 M and 16 M mice, while there were obvious neuronal damages in 20 M and 24 M mice, especially in the 24 M group. Consistent with the behavioral and histological changes in the older mice, the activity of β-galactosidase (β-gal), the levels of ROS and IL-1β, and the expressions of NLRP1, ASC, caspase-1, NOX2, p47phox and p22phox were significantly increased in the cortex and hippocampus in the older 20 M and 24 M mice. Conclusion Our study suggested that NLRP1 inflammasome activation may be closely involved in aging-related neuronal damage and may be an important target for preventing brain aging.

Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats

Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

The mystery of claustral neural circuits and recent updates on its role in neurodegenerative pathology

Introduction The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. Objective Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. Materials and methods A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. Results Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis

Schizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood. Finding new methods to uncover the physiological basis of the mental inabilities related to schizophrenia is an urgent task for modern neuroscience because of the lack of specific therapies for cognitive deficits in the disease. Researchers have begun investigating functional crosstalk between NMDARs and GABAergic neurons associated with schizophrenia at different resolutions. In another direction, the gut microbiota is getting increasing interest from neuroscientists. Recent findings have highlighted the role of a gut-brain axis, with the gut microbiota playing a crucial role in several psychopathologies, including schizophrenia and autism.There have also been investigations into potential therapies aimed at normalizing altered microbiota signaling to the enteric nervous system (ENS) and the central nervous system (CNS). Probiotics diets and fecal microbiota transplantation (FMT) are currently the most common therapies. Interestingly, in rodent models of binge feeding, optogenetic applications have been shown to affect gut colony sensitivity, thus increasing colonic transit. Here, we review recent findings on the gut microbiota–schizophrenia relationship using in vivo optogenetics. Moreover, we evaluate if manipulating actors in either the brain or the gut might improve potential treatment research. Such research and techniques will increase our knowledge of how the gut microbiota can manipulate GABA production, and therefore accompany changes in CNS GABAergic activity.

Molecular and cellular pathways contributing to brain aging

Aging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study

Background Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol overdose-induced seizure and sedation level in male rats. Methods The project was performed with 72 male Wistar rats with an average weight of 200–250 g. The rats were randomly assigned to eight groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) individually or in combination. The rats were monitored for 6 h on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured over a 6-h observation period. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3. Data were analyzed in SPSS software using Kruskal–Wallis, Chi-square, regression analysis, and generalized estimating equation (GEE) tests. The significance level was set at P < 0.05. Results The naloxone-diazepam combination reduced the number, severity, and cumulative duration of seizures compared to tramadol use alone and reduced the number of higher-intensity seizures (level 3, 4) to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures but increased the number of mild seizures (level 2). Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures (level 2). In comparison with the tramadol alone group, the acute quercetin group exhibited higher numbers of mild (level 2) and moderate (level 3) seizures. Chronic quercetin administration significantly increased the number of mild seizures. In the GEE model, all groups had higher sedation levels than the saline only group (P < 0.001). None of the protocols had a significant effect on sedation levels compared to the tramadol group. Conclusion The combined administration of naloxone and diazepam in acute-on-chronic tramadol poisoning can effectively reduce most seizure variables compared to tramadol use alone. However, none of the treatments improved sedation levels.

Distinct behavioral traits and associated brain regions in mouse models for obsessive–compulsive disorder

Background Obsessive–compulsive disorder (OCD) is a mental disease with heterogeneous behavioral phenotypes, including repetitive behaviors, anxiety, and impairments in cognitive functions. The brain regions related to the behavioral heterogeneity, however, are unknown. Methods We systematically examined the behavioral phenotypes of three OCD mouse models induced by pharmacological reagents [RU24969, 8-hydroxy-DPAT hydrobromide (8-OH-DPAT), and 1-(3-chlorophenyl) piperazine hydrochloride-99% (MCPP)], and compared the activated brain regions in each model, respectively. Results We found that the mouse models presented distinct OCD-like behavioral traits. RU24969-treated mice exhibited repetitive circling, anxiety, and impairments in recognition memory. 8-OH-DPAT-treated mice exhibited excessive spray-induced grooming as well as impairments in recognition memory. MCPP-treated mice showed only excessive self-grooming. To determine the brain regions related to these distinct behavioral traits, we examined c-fos expression to indicate the neuronal activation in the brain. Our results showed that RU24969-treated mice exhibited increased c-fos expression in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc), hypothalamus, bed nucleus of the stria terminalis, lateral division, intermediate part (BSTLD), and interstitial nucleus of the posterior limb of the anterior commissure, lateral part (IPACL), whereas in 8-OH-DPAT-treated mice showed increased c-fos expression in the ACC, PrL, IL, OFC, NAc shell, and hypothalamus. By contrast, MCPP did not induce higher c-fos expression in the cortex than control groups. Conclusion Our results indicate that different OCD mouse models exhibited distinct behavioral traits, which may be mediated by the activation of different brain regions.

Linalool odor‐induced analgesia is triggered by TRPA1-independent pathway in mice

We had recently reported that linalool odor exposure induced significant analgesic effects in mice and that the effects were disappeared in olfactory-deprived mice in which the olfactory epithelium was damaged, thus indicating that the effects were triggered by chemical senses evoked by linalool odor exposure. However, the peripheral neuronal mechanisms, including linalool receptors that contribute toward triggering the linalool odor-induced analgesia, still remain unexplored. In vitro studies have shown that the transient receptor potential ankyrin 1 (TRPA1) responded to linalool, thus raising the possibility that TRPA1 expressed on the trigeminal nerve terminal detects linalool odor inhaled into the nostril and triggers the analgesic effects. To address this hypothesis, we measured the behavioral pain threshold for noxious mechanical stimulation in TRPA1-deficient mice. In contrast to our expectation, we found a significant increase in the threshold after linalool odor exposure in TRPA1-deficient mice, indicating the analgesic effects of linalool odor even in TRPA1-deficient mice. Furthermore, intranasal application of TRPA1 selective antagonist did not alter the analgesic effect of linalool odor. These results showed that the linalool odor-induced analgesia was triggered by a TRPA1-independent pathway in mice.

Susceptibility to chronic immobilization stress‐induced depressive-like behaviour in middle‐aged female mice and accompanying changes in dopamine D1 and GABAA receptors in related brain regions

Background Middle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Results We found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS. Conclusions Our results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.