- Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. [Journal Article]
- JNJ Nutr Biochem 2018 Feb 02; 56:16-25
- Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. How...
Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0.25mg/kg) for 9 days. It was found that LYC inhibited LPS-induced memory loss by behavior tests including Y-maze test and Morris water test. Meanwhile, LYC prevented LPS-induced accumulation of Aβ, levels of amyloid precursor protein (APP), and suppressed neuronal β-secretase BACE1 and elevated the expressions of α-secretase ADAM10. Furthermore, LYC down-regulated the expression of IBA-1 (a marker of microglia activation), reduced the levels of inflammatory mediators and inhibited oxidative stress in LPS-treated mice. Moreover, LYC suppressed the phosphorylation of MAPKs, NFκB, and activated Nrf2 signaling pathways in LPS-treated BV2 microglial cells. Therefore, our study indicated that LYC could ameliorate LPS-induced neuroinflammation, oxidative stress, amyloidogenesis and cognitive impairments possibly through mediating MAPKs, NFκB and Nrf2 signaling pathways, indicating that LYC might be a nutritional preventive strategy in neuroinflammation-related diseases such as AD.
- Working Memory And Brain Tissue Microstructure: White Matter Tract Integrity Based On Multi-Shell Diffusion MRI. [Journal Article]
- SRSci Rep 2018 Feb 16; 8(1):3175
- Working memory is a complex cognitive process at the intersection of sensory processing, learning, and short-term memory and also has a general executive attention component. Impaired working memory ...
Working memory is a complex cognitive process at the intersection of sensory processing, learning, and short-term memory and also has a general executive attention component. Impaired working memory is associated with a range of neurological and psychiatric disorders, but very little is known about how working memory relates to underlying white matter (WM) microstructure. In this study, we investigate the association between WM microstructure and performance on working memory tasks in healthy adults (right-handed, native English speakers). We combine compartment specific WM tract integrity (WMTI) metrics derived from multi-shell diffusion MRI as well as diffusion tensor/kurtosis imaging (DTI/DKI) metrics with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests tapping auditory working memory. WMTI is a novel tool that helps us describe the microstructural characteristics in both the intra- and extra-axonal environments of WM such as axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities, allowing a more biophysical interpretation of WM changes. We demonstrate significant positive correlations between AWF and letter-number sequencing (LNS), suggesting that higher AWF with better performance on complex, more demanding auditory working memory tasks goes along with greater axonal volume and greater myelination in specific regions, causing efficient and faster information process.
- A role for tau in learning, memory and synaptic plasticity. [Journal Article]
- SRSci Rep 2018 Feb 16; 8(1):3184
- Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggreg...
Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. Accordingly, tau is a favored therapeutic target for the treatment of these diseases. Given the criticality of tau to dementia's pathogenesis and therapy, it is important to understand the physiological function of tau in the central nervous system. Analysis of Mapt knock out (Mapt-/-) mice has yielded inconsistent results. Some studies have shown that tau deletion does not alter memory while others have described synaptic plasticity and memory alterations in Mapt-/-mice. To help clarifying these contrasting results, we analyzed a distinct Mapt-/-model on a B6129PF3/J genetic background. We found that tau deletion leads to aging-dependent short-term memory deficits, hyperactivity and synaptic plasticity defects. In contrast, Mapt+/-mice only showed a mild short memory deficit in the novel object recognition task. Thus, while tau is important for normal neuronal functions underlying learning and memory, partial reduction of tau expression may have fractional deleterious effects.
- Orchiectomy and letrozole differentially regulate synaptic plasticity and spatial memory in a manner that is mediated by SRC-1 in the hippocampus of male mice. [Journal Article]
- JSJ Steroid Biochem Mol Biol 2018 Feb 13
- Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) con...
Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity. Next, we examined the changes in steroid receptors and steroid receptor coactivator-1 (SRC-1) under these treatments. Finally, we constructed an SRC-1 RNA interference lentivirus and an AROM overexpression lentivirus to explore the roles of SRC-1 under T replacement and AROM overexpression. The results revealed spatial memory impairment only after LET. LET induced more actin depolymerization and greater losses of spines, synapses, and postsynaptic proteins compared with ORX. Moreover, although ERα and ERβ were affected by LET and ORX at similar levels, AR, GPR30, and SRC-1 were dramatically decreased by LET compared with ORX. Finally, the T and AROM overexpression-induced changes in synaptic proteins and actin polymerization were blocked by SRC-1 inhibition. These results demonstrate that testicular androgens play a limited role, whereas local E2 is more important for cognition, which may explain why castrated men such as eunuchs usually do not have cognitive disorders. These results also suggest a pivotal role of SRC-1 in the action of steroids; thus, SRC-1 may serve as a novel therapeutic target for cognitive disorders.
- Neuroprotective effects of valproic acid on brain ischemia are related to its HDAC and GSK3 inhibitions. [Journal Article]
- PBPharmacol Biochem Behav 2018 Feb 13
- Valproic acid (VA) is an antiepileptic that is also used for the treatment of bipolar disorders. The objective was to evaluate the neuroprotective effects of VA on a brain ischemia model. The groups ...
Valproic acid (VA) is an antiepileptic that is also used for the treatment of bipolar disorders. The objective was to evaluate the neuroprotective effects of VA on a brain ischemia model. The groups of male Wistar rats were: SO (sham-operated), ischemic and ischemic treated with VA (25, 50 and 100 mg/kg, p.o.). After anesthesia with ketamine and xilazine, the animals were subjected to clamping of carotid arteries (30 min) and reperfusion. Except for the carotid clamping, the SO group was submitted to the same procedure. On the 7th day, the animals were behaviorally evaluated, euthanized and had their brain dissected for neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and Tukey as the post hoc test. The results showed that VA reversed partly or completely the behavioral (locomotor activity and memory deficits), neurochemical (striatal DA and DOPAC levels, brain nitrite and lipid peroxidation) and immunohistochemical alterations (iNOS, COX-2, HDAC and GSK3) observed in the untreated ischemic group. VA neuroprotective effects are probably related to its anti-inflammatory and antioxidant properties, as well as to HDAC and GSK3 inhibitory effects. These findings stimulate translational studies focusing on VA as a neuroprotective drug to be potentially used in the clinic for several neurological conditions.
- A spatial memory signal shows that the parietal cortex has access to a craniotopic representation of space. [Journal Article]
- EElife 2018 Feb 16; 7
- Humans effortlessly establish a gist-like memory of their environment whenever they enter a new place, a memory that can guide action even in the absence of vision. Neurons in the lateral intrapariet...
Humans effortlessly establish a gist-like memory of their environment whenever they enter a new place, a memory that can guide action even in the absence of vision. Neurons in the lateral intraparietal area (LIP) of the monkey exhibit a form of this environmental memory. These neurons respond when a monkey makes a saccade that brings the spatial location of a stimulus that appeared on a number of prior trials, but not on the present trial, into their receptive fields (RFs). The stimulus need never have appeared in the neuron's RF. This memory response is usually weaker, with a longer latency than the neuron's visual response. We suggest that these results demonstrate that LIP has access to a supraretinal memory of space, which is activated when the spatial location of the vanished stimulus can be described by a retinotopic vector from the center of gaze to the remembered spatial location.
- Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity and Autism Spectrum Disorder without Intellectual Disability. [Journal Article]
- JAJ Abnorm Child Psychol 2018 Feb 15
- Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are commonly comorbid, share genetic liability, and often exhibit overlapping cognitive impairments. Clarification o...
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are commonly comorbid, share genetic liability, and often exhibit overlapping cognitive impairments. Clarification of shared and distinct cognitive effects while considering comorbid symptoms across disorders has been lacking. In the current study, children ages 7-15 years assigned to three diagnostic groups:ADHD (n = 509), ASD (n = 97), and controls (n = 301) completed measures spanning the cognitive domains of attention/arousal, working memory, set-shifting, inhibition, and response variability. Specific processes contributing to response variability were examined using a drift diffusion model, which separately quantified drift rate (i.e., efficiency of information processing), boundary separation (i.e., speed-accuracy trade-offs), and non-decision time. Children with ADHD and ASD were impaired on attention/arousal, processing speed, working memory, and response inhibition, but did not differ from controls on measures of delayed reward discounting, set-shifting, or interference control. Overall, impairments in the ASD group were not attributable to ADHD symptoms using either continuous symptom measures or latent categorical grouping approaches. Similarly, impairments in the ADHD group were not attributable to ASD symptoms. When specific RT parameters were considered, children with ADHD and ASD shared impairments in drift rate. However, children with ASD were uniquely characterized by a wider boundary separation. Findings suggest a combination of overlapping and unique patterns of cognitive impairment for children with ASD as compared to those with ADHD, particularly when the processes underlying reaction time measures are considered separately.
- Memory Rehabilitation in Patients with Epilepsy: a Systematic Review. [Review]
- NRNeuropsychol Rev 2018 Feb 15
- Memory failure is a common clinical concern of patients with epilepsy and is associated with significant functional impairments. Thus, memory rehabilitation is of critical clinical importance. In thi...
Memory failure is a common clinical concern of patients with epilepsy and is associated with significant functional impairments. Thus, memory rehabilitation is of critical clinical importance. In this article, we aimed to systematically evaluate the efficacy of memory rehabilitation in patients with epilepsy. The Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to guide searches, extraction and reporting of data in this review. PsycINFO, Medline and PsychBITE searches yielded 95 studies. Twelve papers met inclusion criteria, reporting outcomes of cognitive or behavioural interventions that specifically targeted the rehabilitation of memory in patients with epilepsy. Methodological rigour was rated using the Single-Case Experimental Design (SCED) scale for single-case studies and a modified version of the Downs and Black checklist for group studies. Twelve prospective studies, nine group (six pre-post design, one waitlist crossover, two randomised controlled trials) and three single-case studies were identified. Eleven of the studies included adults, eight of which involved adults with temporal lobe epilepsy (TLE). One paediatric study was identified. The quality of group studies ranged from 36% (poor) to 72% (good), using the modified Downs and Black checklist. Single-case studies were assessed using the SCED scale and assessed to range in quality from four to seven out to 11. Overall, memory rehabilitation was associated with improved memory function in all studies. Verbal memory outcomes were most commonly examined and associated with improvements. This review found that the level of evidence available to support rehabilitation of memory in patients with epilepsy was generally weak and inconsistent. Nevertheless, studies conducted to date, albeit of limited methodological quality, offer preliminary evidence that memory rehabilitation is associated with improvements in verbal memory in patients with temporal lobe epilepsy. Little is known about the efficacy of memory rehabilitation in patients with non-TLE, children, and other aspects of memory difficulties. Guidelines for future research are proposed.
- The Impact of Age, Background Noise, Semantic Ambiguity, and Hearing Loss on Recognition Memory for Spoken Sentences. [Journal Article]
- JSJ Speech Lang Hear Res 2018 Feb 15; :1-12
- CONCLUSIONS: Our results demonstrate listeners' reliance on domain-general cognitive processes when listening to acoustically challenging speech, even when speech is highly intelligible. Acoustic challenge and semantic ambiguity both reduce the accuracy of listeners' recognition memory for spoken sentences.
New Search Next
- Binge Alcohol Exposure Causes Neurobehavioral Deficits and GSK3β Activation in the Hippocampus of Adolescent Rats. [Journal Article]
- SRSci Rep 2018 Feb 15; 8(1):3088
- Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain incon...
Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris water maze. However, alcohol did not alter the spontaneous locomotor activity which was determined by the open field test. GSK3β is a multi-function serine/threonine protein kinase regulating both neuronal survival and neurogenesis and plays an important role in various neurodegenerative disorders. We have previously shown that GSK3β is a key mediator of alcohol-induced neuron apoptosis in the developing brain. We showed here binge alcohol exposure caused GSK3β activation by inducing dephosphorylation at Ser9 without affecting the phosphorylation of Tyr216 in the hippocampus. Thus, GSK3β may be involved in binge alcohol exposure-induced neuronal damage to the adolescent hippocampus.