The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing. However, little is known about odor representation within its dorsal (DTT) and ventral (VTT) components. To address this need, spontaneous and odor-evoked activity of DTT and VTT neurons was recorded from urethane anesthetized mice and compared to activity recorded from adjacent areas within adjacent caudomedial aspects of the anterior olfactory nucleus (AON). Neurons recorded from DTT, VTT, and AON exhibited odor-selective alterations in firing rate in response to a diverse set of monomolecular odorants. While DTT and AON neurons exhibited similar tuning breadth, selectivity, and response topography, the proportion of odor-selective neurons was substantially higher in the DTT. These findings provide evidence that the tenia tecta may contribute to the encoding of specific stimulus attributes. Further work is needed to fully characterize functional organization of the tenia tecta and its contribution to sensory representation and utilization.
Investigation of human neurodegeneration-related aggregates of beta-amyloid 1-42 (Aβ42) on bdelloid rotifers is a novel interdisciplinary approach in life sciences. We reapplied an organ size-based in vivo monitoring system, exploring the autocatabolism-related alterations evoked by Aβ42, in a glucose-supplemented starvation model. The experientially easy-to-follow size reduction of the bilateral reproductive organ (germovitellaria) in fasted rotifers was rescued by Aβ42, serving as a nutrient source- and peptide sequence-specific attenuator of the organ shrinkage phase and enhancer of the regenerative one including egg reproduction. Recovery of the germovitellaria was significant in comparison with the greatly shrunken form. In contrast to the well-known neurotoxic Aβ42 (except the bdelloids) with specific regulatory roles, the artificially designed scrambled version (random order of amino acids) was inefficient in autocatabolism attenuation, behaving as negative control. This native Aβ42-related modulation of the 'functionally reversible organ shrinkage' can be a potential experiential and supramolecular marker of autocatabolism in vivo.
BACKGROUND:The number of patients with cognitive impairment increases as the population becomes older. This perspective may persist a burden on health care systems unless considered new options of prevention and treatment. The aim of this meta-synthesis is to analyze different systematic reviews on the effectiveness of dual-task training (DTT) on cognition and motor function of different people.METHODS:A systematic search of systematic reviews published until October 2019 was conducted in PubMed/Medline, Scopus and Cochrane databases addressing studies which investigated the effect of DTT compared to control or other intervention on cognitive functions of healthy or unhealthy individuals. Three steps were followed to retrieve studies: reading title, abstract and full text. Checklist Assessing the Methodological Quality of Systematic Reviews (AMSTAR) was used to assess the quality of selected articles.RESULTS:In terms of quality of evidence, according to AMSTAR, 62.5 % of the reviews were rated as being "low" and 37.5 % were graded as "moderate" quality. Two main themes were identified among the studies' outcomes: Improvement on mobility performance or postural stability; and beneficial effect on cognitive function. In terms of effect size, there were reported an important variation, having more significant results for findings involving mobility and modest effect for findings regarding cognitive function.CONCLUSION:People with different clinical conditions could benefit from dual-task training. The benefits may encompass general cognitive functions, memory, physical performance, gait and balance, to name a few aspects.
Sirtuins (SIRTs) are a protein family with high preservation degree among evolutionary scale. SIRTs are histone deacetylases regulatory enzymes of genetic material deeply involved in numerous physiological tasks including metabolism, brain function and aging. Mammals sirtuins comprise seven enzymatic components (SIRT1–SIRT7). The highest studied sirtuin is SIRT1, which plays an essential position in the prevention and evolution of neuro-disorders. Resveratrol (3,5,4-trihydroxystylbene) (RSV) is a polyphenol, which belongs to a family compounds identified as stilbenes, predominantly concentrated in grapes and red wine. RSV is the must studied Sirtuin activator and is used as food supplementary compound. Resveratrol exhibits strong antioxidant activity, reducing free radicals, diminishing quinone-reductase-2 activity and exerting positive regulation of several endogenous enzymes. Resveratrol is also able to inhibit pro-inflammatory factors, reducing the stimulation of the nuclear factor kB (NF-kB) and the release of endogenous cytokines. Resveratrol treatment can modulate multiple signaling pathway effectors related to programmed cell death, cell survival, and synaptic plasticity. In this context, the present review looks over news and the role of Sirtuins activation and resveratrol effects on modulating target genes, cognition and neurodegenerative disorders.
Coordination between the urinary bladder (BL) and external urethral sphincter (EUS) is necessary for storage and elimination of urine. In rats interneuronal circuits at two levels of the spinal cord (i.e., L6-S1 and L3-L4) play an important role in this coordination. In the present experiments retrograde trans-synaptic transport of pseudorabies virus (PRV) encoding fluorescent markers (GFP and RFP) was used to trace these circuits. To examine the relative localization of EUS-related and BL-related interneuronal populations we injected PRV-GFP into the EUS and PRV-RFP into the BL wall. The PRV infected populations of spinal interneurons were localized primarily in the dorsal commissure (DCM) of L6/S1 and in a hypothesized lumbar spinal coordinating center (LSCC) in L3/L4 above and lateral to central canal (CC). At both sites colocalization of markers occurred in a substantial number of labeled interneurons indicating concomitant involvement of these double-labelled neurons in the EUS- and BL-circuits and suggesting their role in EUS-BL coordination. Intense GFP or RFP fluorescent was detected in a subpopulation of cells at both sites suggesting that they were infected earlier and therefore likely to represent first order, primary interneurons that directly synapse with output neurons. Larger numbers of weakly fluorescent neurons that likely represent second order interneurons were also identified. Within the population of EUS-related first order interneurons only 3–8 % exhibited positive immunoreaction for an early transcription factor Pax2 specific to GABAergic and glycinergic inhibitory neurons suggesting that the majority of interneurons in DCM and LSCC projecting directly to the EUS motoneurons are excitatory.
Intracerebral hemorrhage (ICH) may be caused by trauma, aneurysm and arteriovenous malformation, as can any bleeding within the intracranial vault, including brain parenchyma and adjacent meningeal spaces (aneurism and atreovenous malformation). ICH is the cerebral stroke with the least treatable form. Over time, intraventricular hemorrhage (IVH) is associated with ICH, which contributes to hydrocephalus, and the major cause of most hemorrhagic death (Due to the cerebral hemorrhage and post hemorrhagic surgeries). Most patients suffer from memory impairment, grip strength, posture, and cognitive dysfunctions attributable to cerebral hemorrhage or post-brain hemorrhagic surgery. Nevertheless, a combined model of ICH based IVH is not present pre-clinically. Autologous blood (ALB) injection (20 μl/5 min) in the rat brain triggers hemorrhage, such as factors that further interfere with the normal functioning of neuroinflammatory cytokines, oxidative stress, and neurotransmitter dysfunction, such as CoQ10 insufficiency and dysregulation of mitochondrial ETC-complexes. For the prevention of post-brain hemorrhagic behavioral and neurochemical dysfunctions, there is no specific drug treatment available, only available therapy used to provide symptomatic relief. The current study reveals that long-term administration of Solanesol (SNL) 40 and 60 mg/kg alone and in combination with available drug therapy Donepezil (DNP) 3 mg/kg, Memantine (MEM) 20 mg/kg, Celecoxib (CLB) 20 mg/kg, Pregabalin (PGB) 30 mg/kg, may provide the neuroprotective effect by improving behavioral and neurochemical deficits, and gross pathological changes in ALB induced combined experimental model of ICH-IVH in post brain hemorrhagic conditions in rats. Thus, SNL can be a potential therapeutic approach to improve neuronal mitochondrial dysfunction associated with post brain hemorrhagic behavioral and neurochemical alterations.
Correlated spontaneous activity propagating over a wide region of the central nervous system is expressed during a specific period of embryonic development. We previously demonstrated using an optical imaging technique with a voltage-sensitive dye that this wave-like activity, which we referred to as the depolarization wave, is fundamentally involved in the early process of synaptic network formation. We found that the in ovo application of bicuculline/strychnine or d-tubocurarine, which blocked the neurotransmitters mediating the wave, significantly reduced functional synaptic expression in the brainstem sensory nucleus. This result, particularly for d-tubocurarine, an antagonist of nicotinic acetylcholine receptors, suggested that prenatal nicotine exposure associated with maternal smoking affects the development of neural circuit formation by interfering with the correlated wave. In the present study, we tested this hypothesis by examining the effects of nicotine on the correlated activity and assessing the chronic action of nicotine in ovo on functional synaptic expression along the vagal sensory pathway. In ovo observations of chick embryo behavior and electrical recording using in vitro preparations showed that the application of nicotine transiently increased embryonic movements and electrical bursts associated with the wave, but subsequently inhibited these activities, suggesting that the dominant action of the drug was to inhibit the wave. Optical imaging with the voltage-sensitive dye showed that the chronic exposure to nicotine in ovo markedly reduced functional synaptic expression in the higher-order sensory nucleus of the vagus nerve, the parabrachial nucleus. The results suggest that prenatal nicotine exposure disrupts the initial formation of the neural circuitry by inhibiting correlated spontaneous wave activity.
Various mutations in the SLC25A46 gene have been reported in mitochondrial diseases that are sometimes classified as type 2 Charcot-Marie-Tooth disease, optic atrophy, and Leigh syndrome. Although human SLC25A46 is a well-known transporter that acts through the mitochondrial outer membrane, the relationship between neurodegeneration in these diseases and the loss-of-function of SLC25A46 remains unclear. Two Drosophila genes, CG8931 (dSLC25A46a) and CG5755 (dSLC25A46b) have been identified as candidate homologs of human SLC25A46. We previously characterized the phenotypes of pan-neuron-specific dSLC25A46b knockdown flies. In the present study, we developed pan-neuron-specific dSLC25A46a knockdown flies and examined their phenotypes. Neuron-specific dSLC25A46a knockdown resulted in reduced mobility in larvae as well as adults. An aberrant morphology for neuromuscular junctions (NMJs), such as a reduced synaptic branch length and decreased number and size of boutons, was observed in dSLC25A46a knockdown flies. Learning ability was also reduced in the larvae of knockdown flies. In dSLC25A46a knockdown flies, mitochondrial hyperfusion was detected in NMJ synapses together with the accumulation of reactive oxygen species and reductions in ATP. These phenotypes were very similar to those of dSLC25A46b knockdown flies, suggesting that dSLC25A46a and dSLC25A46b do not have redundant roles in neurons. Collectively, these results show that the depletion of SLC25A46a leads to mitochondrial defects followed by an aberrant synaptic morphology, resulting in locomotive defects and learning disability. Thus, the dSLC25A46a knockdown fly summarizes most of the phenotypes in patients with mitochondrial diseases, offering a useful tool for studying these diseases.
This study investigated the impact of a brief meditation workshop on a sample of 223 novice meditators. Participants attended a three-day workshop comprising daily guided seated meditation sessions using music without vocals that focused on various emotional states and intentions (open focus). Based on the theory of integrative consciousness, it was hypothesized that altered states of consciousness would be experienced by participants during the meditation intervention as assessed using electroencephalogram (EEG). Brainwave power bands patterns were measured throughout the meditation training workshop, producing a total of 5616 EEG scans. Changes in conscious states were analysed using pre-meditation and post-meditation session measures of delta through to gamma oscillations. Results suggested the meditation intervention had large varying effects on EEG spectra (up to 50 % increase and 24 % decrease), and the speed of change from pre-meditation to post-meditation state of the EEG co-spectra was significant (with 0.76 probability of entering end-meditation state within the first minute). There was a main 5 % decrease in delta power (95 % HDI = [-0.07, -0.03]); a global increase in theta power of 29 % (95 % HDI = [0.27, 0.33]); a global increase of 16 % (95 % HDI = [0.13, 0.19]) in alpha power; a main effect of condition, with global beta power increasing by 17 % (95 % HDI = [0.15, 0.19]); and an 11 % increase (95 % HDI = [0.08, 0.14]) in gamma power from pre-meditation to end-meditation. Findings provided preliminary support for brief meditation in altering states of consciousness in novice meditators. Future clinical examination of meditation was recommended as an intervention for mental health conditions particularly associated with hippocampal impairments.
To evaluate the acute effects of ingestion of 500 mg of caffeine in addition to aerobic exercise on the optimization of cognitive attention tasks and simple reaction time. Twenty men were randomly divided into two groups, caffeine (CAF) and placebo (PLA), and underwent cardiopulmonary exercise testing and cognitive testing (D2SLK, D2GZ, D2F% and TRS). Then, both ingested 500 mg of caffeine or placebo (double blind), and after 60 min performed a 30-minute continuous exercise session at 70 % VO2Max. Cognitive tests were repeated immediately after exercise, and after 30 min. D2SLK, D2GZ, D2F% and TRS scores were compared by repeated measures ANOVA. The magnitude of the effect was established, and it was considered meaningful p = 0.05. CAF is able to alter D2SLK and also reduce D2F% (0.001 - moderate effect, 0.82) and improve the task after 30 min of exercise (p = 0.014 - moderate effect 0.95). The TRS showed significant gains for the CAF group compared to PLA (0.000 - high effect 1.76). Caffeine induces significant effects in attention and reaction time domains independent of the effect of aerobic exercise.
The experience of pain involves the activation of multiple brain areas. Pain-specific activity patterns within and between these local networks remain, however, largely unknown. We measured neuronal network oscillations in different relevant regions of the mouse brain during acute pain, induced by subcutaneous injection of capsaicin into the left hind paw. Field potentials were recorded from primary somatosensory cortex, anterior cingulate cortex (ACC), posterior insula, ventral posterolateral thalamic nucleus, parietal cortex, central nucleus of the amygdala and olfactory bulb. Analysis included power spectra of local signals as well as interregional coherences and cross-frequency coupling (CFC). Capsaicin injection caused hypersensitivity to mechanical stimuli for at least one hour. At the same time, CFC between low (1−12 Hz) and fast frequencies (80−120 Hz) was increased in the ACC, as well as interregional coherence of low frequency oscillations (< 30 Hz) between several networks. However, these changes were not significant anymore after multiple comparison corrections. Using a variable selection method (elastic net) and a logistic regression classifier, however, the pain state was reliably predicted by combining parameters of power and coherence from various regions. Distinction between capsaicin and saline injection was also possible when data were restricted to frequencies <30 Hz, as used in clinical electroencephalography (EEG). Our findings indicate that changes of distributed brain oscillations may provide a functional signature of acute pain or pain-related alterations in activity.
Early in the postnatal period, motoneuron axon stimulation can excite motor networks in the spinal cord. Here we tested if these excitatory effects changed across early postnatal development up to postnatal day (P) 24 by when mice are capable of weight-bearing locomotion and locomotor networks are considered functionally mature. This was accomplished in the isolated spinal cord preparation using ventral root evoked entrainment of disinhibited bursts. Ventral root evoked entrainment was defined and characterized over the first 2 weeks of postnatal development, and was found to decline over this period, but entrainment could still be detected in mice as old as P24. Disinhibited bursting could be elicited, and dorsal root evoked entrainment could be recorded as late as P39 and remained unchanged in effectiveness, suggesting that poor tissue viability may not be the cause of the decline in ventral root evoked entrainment. Pharmacological experiments performed on younger animals established that dopamine D2 receptor antagonists and mGluR1 agonists both enhanced ventral root evoked entrainment. In conclusion, the motoneuronal inputs to spinal motor networks via the excitatory pathway is modulated by dopamine and metabotropic glutamate receptors and may be under powerful inhibitory control, which may explain why there is a developmental decline in entrainment.
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Background: Diabetes mellitus (DM) is a public health problem, which requires enhanced self-care in order to avoid complications. However, cognitive impairment can reduce these abilities and may affect health literacy (HL) of patients in terms to understand and apply information. Therefore, this study evaluated the correlation between cognitive condition and HL related to medication adherence, physical activity and nutritional status among people living with DM. Methods: A cross-sectional study was carried out among elderly people (>= 60 years old) with DM. The cognitive condition was evaluated using the Mini-Mental State Examination (MMSE) and the HL using the following questionnaires: Literacy Assessment for Diabetes (LAD-60), Nutritional Literacy among People with Diabetes (NLD), Health Literacy on the Practice of Physical Activities among Diabetics (HLPPA - D), and Health Literacy regarding Drug Adherence among Diabetics (HLDA-D). Sociodemographic and biochemical profile was also evaluated. Spearman correlation was used (p < 0.05). Results: 187 individuals with DM were included. Regarding laboratory analyses, insulin dosage had a mean value of 12.3 microUI/mL (SD:+/- 15.7), mean blood glucose was 148.1 mg/dl (SD:+/- 59.7) and mean HbA1c was 7.54 % (SD:+/- 1.8). In the correlation analysis, higher age and lower income were weakly correlated with lower cognitive level. No correlation was identified for biochemical variables and cognitive condition. A positive and weak correlation between cognition and HL was observed in the studied population. Conclusions: In older people living with DM the cognitive condition is correlated to specific topics of HL (nutritional status, physical activity and medication adherence).
BACKGROUND:Mental disorders increase the risk factor for developing physical comorbidity conditions, such as cardiometabolic diseases. There is a high prevalence of multimorbidity and polypharmacy in the elderly population which hampers clinical response. Studies have shown that this positive correlation between the aging process and enhancement of physical comorbidities is especially high among older adults who live in low or middle income countries.OBJECTIVE:To investigate the association between physical disease comorbidities and polypharmacy in older adults with a clinical diagnosis of Alzheimer's disease (AD), mild cognitive impairment (MCI) or major depressive disorder (MDD), living in a middle income country.METHODS:Cross-sectional study of community-dwelling elderly individuals who are cognitively healthy and those with AD, MCI, or MDD. The severity scale of the Charlson Comorbidity Index (CCI) was calculated to classify the severity of comorbidity condition. Logistic regression model (unadjusted and adjusted for age) were used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for cardiometabolic comorbidity (hypertension, diabetes, dyslipidemia and overweight), and polypharmacy.RESULTS:Although there was not an increased risk of hypertension, diabetes, and obesity among the groups, elderly people with mental disorders presented higher odds for polypharmacy condition. Polypharmacy was significantly higher for all groups in comparison with cognitively healthy participants: AD (OR 22.00, 95 % CI 6.11-79.11), MDD (OR 14.73, 95 % CI 3.69-58.75) and MCI (OR 10.31, 95 % CI 2.44-43.59). Elderly patients with AD presented more severe comorbidities and higher risks for dyslipidemia.CONCLUSION:Elderly patients with depression, dementia and mild cognitive impairment have considerably higher odds for polypharmacy. People with dementia also have greater comorbidity severity than those who are cognitively healthy. In middle income countries, there is an urgent need to focus on promoting age-appropriate health approaches for the elderly with mental illness to prevent the development of aggravated cardiometabolic conditions and polypharmacy.
Hypoxic-ischaemic brain injury is a major cause of morbidity and mortality internationally. Using an in vitro isolated cortex model, this study investigated the optimal cerebrospinal fluid oxygenation parameters for rescuing metabolically challenged cortical tissue. In particular, we asked whether maximizing oxygen content with oxygen nanobubbles could support improved tissue recovery. Mouse cortical slices were metabolically starved, followed by recovery in artificial cerebrospinal fluid (aCSF) containing different levels of dissolved oxygen ranging from mean(SD) 2(0.5) to 39(1.0) mg/L; with and without oxygen nanobubbles. Tissue recovery was assessed by quantifying and comparing the amplitude, length, high frequency content and event frequency of seizure-like events generated in no-magnesium aCSF at the beginning and end of the protocol. In general, there was improved recovery with increasing oxygen content up to 25-34 mg/L. The outcome of slices recovered in nanobubbled aCSF was no different to conventionally oxygenated slices with similar dissolved oxygen content. Dissolved oxygen content above 34 mg/L afforded no additional benefit. In conclusion, aCSF dissolved oxygen content of approximately 30 mg/L is optimal for cortical tissue recovery from metabolic starvation, which is easily achievable using conventional oxygenation methods. Oxygen in the form of nanobubbles does not appear to be readily available for tissue oxidative processes in this model.
BACKGROUND:Instrumental activities of daily living (IADLs) ability impairments are clearly related to cognitive and motor decline, as well as to the progression of Dementia. However, more low-cost assessments are necessary to better understand the process of IADL in patients with Dementia. OBJECTIVE:To compare cognitive, motor and cognitive-motor performance at different stages of dependence on IADL in patients with Dementia. METHODS:Dementia patients (n = 53, age range: 63-94) and healthy older adults (n = 39, age range: 62-97) were included, and those with Dementia were separated into IADL 1 (n = 18), IADL 2 (n = 17), IADL 3 (n = 18). All groups performed cognitive (Trail making test A, semantic verbal fluency, and Stroop test), motor (sit to stand, aerobic steps, and 8-foot up-and-go), and cognitive-motor tests (dual-task, and spatial navigation). One-way ANOVA, Kruskal-Wallis, and Bonferroni post-hoc tests were used to compare groups. Also, an effect size (ES) has been applied to evaluate differences among the dementia groups while the healthy older adults were used as a reference group. RESULTS:Only cognitive-motor and cognitive tests showed significant differences among groups (IADL 1 x IADL 2 x IADL 3). Compared with the healthy group, the ES analysis exposed that patients in different stages of IADL showed the worst performance on tests combining motor and cognitive demand, but not for motor and cognitive function separately. CONCLUSION:Poor dual-task and spatial navigation abilities are present in partial dependence in IADL, and these tasks should be considered as a functionality screening tool in patients with Dementia.
Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma.
Calorie restriction (CR) has been considered the most effective non-pharmacological intervention to counteract aging-related diseases and improve longevity. This intervention has shown beneficial effects in the prevention and treatment of several chronic diseases and functional declines related to aging, such as Parkinson's, Alzheimer's, and neuroendocrine disorders. However, the effects of CR on cognition show controversial results since its effects vary according to intensity, duration, and the period of CR. This review focuses on the main studies published in the last ten years regarding the consequences of CR on cognition in different neurological diseases and conditions of experimental animals. Also, possible CR mimetics are discussed. These findings highlight the potential beneficial effects of CR of up to 40 % on cognition when started early in life in non human animals.
PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins, a large family of proteins that act as axonal guidance cues during nervous system development. However, there are limited studies on PlxnA1 function in neurobehavior. The present study examined if PlxnA1 deficiency leads to behavioral abnormalities in BALB/cAJ mice. PlxnA1 knockout (KO) mice were generated by homologous recombination and compared to wild type (WT) littermates on a comprehensive battery of behavioral tests, including open field assessment of spontaneous ambulation, state anxiety, and grooming, home cage grooming, the wire hang test of muscle strength, motor coordination on the rotarod task, working memory on the Y maze alternation task, cued and contextual fear conditioning, anxiety on the elevated plus maze, sociability to intruders, and sensory processing as measured by prepulse inhibition (PPI). Measures of motor performance, working memory, fear memory, and sociability did not differ significantly between genotypes, while PlxnA1 KO mice displayed excessive self-grooming, impaired PPI, and slightly lower anxiety. These results suggest a crucial role for PlxnA1 in the development and function of brain regions controlling self-grooming and sensory gating. PlxnA1 KO mice may be a valuable model to investigate the repetitive behaviors and information processing deficits characteristic of many neurodevelopmental and psychiatric disorders.
