Neuroscience

In rodents, exploring through continuous whisking is a process resulted from sensorimotor networking among different layers of somatosensory cortex (SC) such as layer 5 (L5) or barrel field, and regions like the nucleus basalis of Meynert (NBM). NBM is densely packed with cholinergic fibers and its dysfunction leads to diminished acetylcholine release within SC, tactile deficits and Alzheimer's disease (AD)-like memory impairment. Using extracellular single-unit recording, we investigated mechanisms underlying changes in response characteristics of L5b neurons to single or paired deflection of selected principle and adjacent whiskers (PW and AW), following NBM electrical stimulation in normal rats or ibotenic acid-induced NBM lesion leading to potential tactile deficiency and memory loss during passive avoidance learning (PAL) in AD-like neuropathology. Our results indicated that NBM electrical stimulation decreased ON and OFF response magnitude in nearly half of the units upon vibrissal deflection. The larger the response was evoked to whisker deflection before NBM stimulation, the smaller it gets after stimulation. Neuronal spontaneous activity was not changed with NBM stimulation or lesion. Leading to more sublinear response summation and decreased condition-test ratio, NBM lesion decreased ON response magnitude and facilitation, increased AW surround inhibition in paired whisker deflection, increased excitatory and decreased inhibitory receptive fields, weakened information processing during whisking, and resulted in AD-like declined PAL performance. These findings provide further understandings to develop translational approaches in precision therapeutics to target highly specific regions such as NBM or SC, and pathways like cholinergic system involved in tactile and memory deficits in AD.

The oxytocinergic system influences attentional bias towards emotional cues and feedback-based learning. Considering a tag single-nucleotide polymorphism (SNP) found through analysis of an intronic haplotype in the oxytocin receptor (OXTR) gene, we investigated the effect of oxytocin on risky decision-making via the Iowa Gambling Task (IGT). Young healthy males received intranasal oxytocin or placebo, and the IGT was performed where raw scores, net scores and total time were recorded, and ratio of advantageous to disadvantageous choices was calculated. Using PCR-pyrosequencing, a 761 bp target sequence in the OXTR gene was amplified and sequenced after the extraction of whole blood DNA. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all 14 SNPs in the intronic region were determined based on D' and LOD values, and rs2254295 with the highest LD was indicated as the tag SNP. GTT was shown to have the highest frequency among the found haplotypes. Oxytocin group and participants with the TT genotype demonstrated a significantly increased raw score, net score and advantageous choices, whereas the total time was not influenced remarkably. This means that oxytocin significantly reduced the risk taking in decision-making, and participants with the TT genotype had less premature or risky decisions than those with the CT and CC genotypes. rs2254295 may modulate the function or expression of the OXTR gene, implying that T allele may increase the expression of the OXTR gene compared to C allele. We suggest that oxytocin may remarkably moderate the risk attitude and its consequences during uncertain decision-making.

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough. In this study, we assessed acute (1 day) and chronic (21 days) effects of intraperitoneally administered ghrelin (at different doses of 1, 10 and 20 μg/kg) during a 12-h fasting period in rats using glucose oxidase method and direct sandwich ELISA (the Enzyme-Linked Immunosorbent Assay) and then compared the effects of exogenous ghrelin on blood glucose and insulin levels on day 21 with those on day 1. The results showed that acute ghrelin administration markedly increased fasting plasma glucose at doses of 1 and 10 μg/kg as well as insulin levels at 1 μg/kg in comparison to control values. Ghrelin (at 1 μg/kg) altered plasma glucose but not insulin levels on the 21st day compared to control values. In addition, the comparison of the influence of ghrelin administration on plasma glucose and insulin levels on day 21 with those on the first day revealed that the chronic administration of ghrelin notably decreased plasma glucose and insulin levels relative to the acute ghrelin treatment. These findings indicate that hyperglycemia and hyperinsulinemia caused by the exogenous ghrelin during acute treatment are temporary and prolonged treatment with ghrelin regulates plasma glucose and restores insulin to normal levels, suggesting a possible role for ghrelin in improving insulin resistance.

Alzheimer's disease (AD), as a common age-related dementia, is a progressive manifestation of cognitive decline following synaptic failure resulted majorly by senile plaques composed of deposits of amyloid beta (Aβ). Ghrelin is a multifunctional peptide hormone with receptors present in various brain tissues including hippocampus and has been associated with neuroprotection, neuromodulation, and memory processing. Here, we investigated the neuroprotective and therapeutic effects of intracerebroventricular (icv) ghrelin infusion for 2 weeks on passive avoidance learning (PAL), memory retention, and synaptic plasticity in the hippocampal dentate gyrus (DG) and CA1 of both normal rats and Aβ1-42-induced neurotoxicity in AD model. Male Wistar rats were evaluated for their passive memory performance using a shuttle box while some groups had already received Aβ1-42 and/or chronic ghrelin. Using field potential recording, the induction of short-and long-term potentiation (STP and LTP) was studied in DG granule cells along with the LTP changes in CA1 pyramidal neurons through stimulation of the medial perforant path (mPP) and Schaffer collaterals (SCs), respectively. Our results demonstrated that chronic ghrelin treatment not only improved memory processing and retrieval in normal rats during the PAL task, but also promoted memory retention and alleviated memory loss by amelioration of Aβ1-42-induced synaptic plasticity impairment in AD subjects through augmentation of field excitatory postsynaptic potential (fEPSP) slope that led to LTP restitution in both the mPP-DG and the CA3-CA1 synapses. Meanwhile, STP was not significantly changed, meaning that although ghrelin enhanced postsynaptic excitability in DG, it did not change presynaptic transmitter release significantly. This suggests the involvement of postsynaptic mechanisms in long-term ghrelin-enhanced memory. In conclusion, it can be inferred that chronic ghrelin administration has an auspicious therapeutic value for impaired cognitive performance and memory deficits in AD-like neuropathology.

Cognitive dysfunction related to opioid use disorder (OUD) requires investigation of the interconnected network of cognitive domains through behavioral experiments and graph data modeling. Here, we conducted n-back, selective and divided attention, and Wisconsin card sorting tests and then reconstructed the interactive cognitive network of subscales or domains for opioid users and non-users to identify the most central cognitive functions and their connections using graph model analysis. Then, each network was analyzed topologically based on the betweenness and closeness centrality measures. Results from the opioid users’ network show that in the divided attention module, the reaction time and the number of commission errors were the most central subscales of cognitive function. Whereas in non-users, the number of correct responses and commission errors were the most central cognitive measure. These findings corroborate that opioid users show impaired divided attention as higher rea...

Science folks unanimously agree about a fixed definition for "Theory of Mind"! That I think is a philosophical paradox as theory of mind has this very pivotal cannon of being open in empathizing and understanding different beliefs through attribution of mental state as in beliefs, intentions, knowledge and

Introduction: Cognitive dysfunction related to opioid use disorder (OUD) requires investigation of the interconnected network of cognitive domains through behavioral experiments and graph data modeling.

Methods: We conducted n-back, selective and divided attention, and Wisconsin card sorting tests and reconstructed the interactive cognitive network of subscales or domains for individuals who use opioids and controls to identify the most central cognitive functions and their connections using graph model analysis. Each two subscales with significant correlations were connected by an edge that incorporated in formation of interactive networks. Each network was analyzed topologically based on the betweenness and closeness centrality measures.

Results: Results from the network reconstructed for individuals who use opioids show that in the divided attention module, reaction time and number of commission errors were the most central subscales of cognitive function. Whereas in controls, the number of correct responses and commission errors were the most central cognitive measure. We found that the subscale measures of divided attention module are significantly correlated with those of other tests. These findings corroborate that persons who use opioids show impaired divided attention as higher reaction time and errors in performing tasks. Divided attention is the most central cognitive function in both OUD subjects and controls, although differences were observed between the two groups in various subscales.

Discussion: Although equal proportions of males and females may be used in future studies, divided attention and its subscales may be the most promising target for cognitive therapies, treatments and rehabilitation as their improvement can enhance overall cognitive domain performance.

As a complex neurodevelopmental disorder, autism affects children in three major cognitive domains including social interactions, language learning and repetitive stereotyped behaviors. Abnormal regulation of cell proliferation in the brain during the embryonic period via the TGF-β signaling pathway and TRIM33 gene that encodes a protein with a corepressor and regulatory role in this pathway has been considered as an etiology for autism. Here, we investigated the association of a variation of TRIM33 with autism symptoms at levels of mRNA and protein expression. We used Autism Diagnostic Interview-Revised (ADI-R) and Childhood Autism Rating Scale (CARS) as behavioral diagnostic tools. Normal and autistic children were genotyped for a TRIM33 polymorphism (rs11102807), and then expression was assessed at transcriptional and translational levels. Results demonstrated that the frequency of the homozygous A allele (AA genotype of rs11102807) was significantly higher in children with autism (P < 0.001), whereas carriers of the G allele were mostly among healthy individuals. Children homozygous for the rs11102807 A allele were associated with an increase in CARS and ADI-R scores, indicating a significant correlation with autism symptoms. TRIM33 gene expression at both mRNA (P < 0.01) and protein (P < 0.001) levels was significantly higher in controls compared to autistic children. A remarkable association between higher TRIM33 gene expression at the transcriptional level and lower scores for both CARS and ADI-R was observed in non-autistic children. It seems that rs11102807 modulates the function and expression of the TRIM33 gene, implying that the A allele may increase the risk of autism in children by reducing gene expression and altering the TGF-β signaling pathway.

Basso et al. Chronic Exercise, Mood and Cognition motivation as well as decreased stress and disordered eating. Our findings are some of the first to indicate that in middle-aged moderately-fit adults, continuing to increase exercise levels in an already ongoing fitness regimen is associated with additional benefits for both psychological and cognitive health.

Ovarian cancer remains a deadly disease and its recurrence disease is due in part to the presence of disseminating ovarian cancer aggregates not removed by debulking surgery. During dissemination in a dynamic ascitic environment, the spheroid cells’ metabolism is characterized by low respiration and fragmented mitochondria, a metabolic phenotype that may not support secondary outgrowth after adhesion. Here, we investigated how adhesion affects cellular respiration and substrate utilization of spheroids mimicking early stages of secondary metastasis. Using different glucose and oxygen levels, we investigated cellular metabolism at early time points of adherence (24 h and less) comparing slow and fast-developing disease models. We found that adhesion over time showed changes in cellular energy metabolism and substrate utilization, with a switch in the utilization of mostly glutamine to glucose but no changes in fatty acid oxidation. Interestingly, low glucose levels had less of an imp...

Increased difficulty with speech, language, and communication in the case of sex chromosome trisomies may be associated with an extra gene on the X and Y chromosomes. KS individuals show restricted material processing speed, verbal fluency, and verbal material memory, which are linked to difficulties in word comprehension. The neurexin-neurologin hypothesis shows that over-expression of neuroligin could impair synaptic regulation when in conjunction with a CNTNAP2 risk variant, thus stunting language development. KS was also noted with impaired cognitive functioning and theorized that the X chromosome may be associated in hemispheric lateralization for language. Due to its limited diagnosis, there remains to be limited knowledge of phenotypic expression and health management in KS. Studying sex chromosome trisomies can shed light to genetic mechanisms underlying language and communication difficulties that extend beyond KS. With increased awareness of the nuances to Klinefelter features in the literature, families and pediatricians can show that the challenges that initially come with Klinefelter can be overcome so that individuals with 47,XXY can live a healthy life.