Neural Plasticity最新文献

Hippocampal cell death and cognitive dysfunction are common following global cerebral ischemia across all ages, including children. Most research has focused on preventing neuronal death. Restoration of neuronal function after cell death is an alternative approach (neurorestoration). We previously identified transient receptor potential M2 (TRPM2) ion channels as a potential target for acute neuroprotection and delayed neurorestoration in an adult CA/CPR mouse model. Cardiac arrest/cardiopulmonary resuscitation (CA/CPR) in juvenile (p20-25) mice was used to investigate the role of ion TRPM2 channels in neuroprotection and ischemia-induced synaptic dysfunction in the developing brain. Our novel TRPM2 inhibitor, tatM2NX, did not confer protection against CA1 pyramidal cell death but attenuated synaptic plasticity (long-term plasticity (LTP)) deficits in both sexes. Further, in vivo administration of tatM2NX two weeks after CA/CPR reduced LTP impairments and restored memory function. These data provide evidence that pharmacological synaptic restoration of the surviving hippocampal network can occur independent of neuroprotection via inhibition of TRPM2 channels, providing a novel strategy to improve cognitive recovery in children following cerebral ischemia. Importantly, these data underscore the importance of age-appropriate models in disease research.

Lipotoxicity of palmitic acid (PA) or high-fat diets has been reported to increase endoplasmic reticulum (ER) stress and autophagy in peripheral tissue as well as apoptotic cell death. It also can lead to an AD-like pathological pattern. However, it has been unknown that PA-induced ER stress and autophagy are involved in the regulation of neuroplastic abnormalities. Here, we investigated the roles of ER stress and autophagy in apoptosis and neuroplasticity-related protein expression in PA-treated prefrontal cells. Prefrontal cells dissected from newborn Sprague-Dawley rats were treated with PA compound with ER stress inhibitor 4-phenylbutyric acid (4-PBA) and autophagy inhibitor 3-methyladenine (3-MA) or PA alone. PA promoted ER stress and autophagy and also cause apoptosis as well as a decline in the expression of neuroplasticity-related proteins. Inhibition of ER stress decreased the expressions of neuroplasticity-related proteins and reduced autophagy activation and apoptosis in PA-treated prefrontal cells. Inhibition of autophagy exacerbated apoptosis and enhanced ER stress in PA-treated prefrontal cells. The present study illustrated that both ER stress and autophagy could be involved in apoptosis and decreased neuroplasticity-related proteins, and the interaction between ER stress and autophagy may play a critical role in apoptosis in PA-treated prefrontal cells. Our results provide new insights into the molecular mechanisms in vitro of lipotoxicity in obesity-related cognitive dysfunction.

Working memory (WM) is one of the most investigated cognitive functions albeit the extent to which individual characteristics impact on performance is still unclear, especially when older adults are involved. The present study considers repeated practice of a visual N-Back task with three difficulty levels (1-, 2-, and 3-Back) in healthy young and older individuals. Our results reveal that, for both age groups, the expected mental fatigue was countered by a learning effect, in terms of accuracies and reaction times, which turned out to benefit females more than males, for all three N-Back levels. We conclude that future WM studies, in particular when relying on repeated N-Back sessions, should account for learning effects in relation to mental fatigue and gender, in both young and older adults.

Background: In recent years, a growing number of researchers showed significant interest in psychological and social interventions to manage chronic musculoskeletal (MSK) pain. Cognitive and emotional empathy is an attractive and valuable sociopsychological factor that may provide protection and resilience against chronic MSK pain. However, its effect on outpatients remains underexplored.

Objective: To compare the empathy ability between chronic MSK pain outpatients and healthy controls and explore the relationship between cognitive/emotional empathy and chronic pain.

Methods: Patients with chronic MSK pain (n = 22) and healthy controls (n = 26) completed the pain assessment and empathy ability task, utilizing a multidimensional empathy assessment tool with satisfactory reliability and validity (i.e., the Chinese version of the Multifaceted Empathy Test (MET-C)).

Results: The data indicated that the chronic MSK pain outpatients had impaired cognitive empathy (i.e., lower squared cognitive empathy accuracy: Student's t = -2.119, P = 0.040, and longer task completion time: Student's t = 3.382, P = 0.002) compared to healthy controls, and cognitive empathy was negatively correlated with pain intensity (r = -0.614, P = 0.002). Further, the impaired cognitive empathy was present in identifying positive, but not negative emotions.

Conclusion: These results indicate that chronic MSK pain is associated with impaired empathy ability. Our studies contribute to offering a potential direction for developing psychosocial interventions to treat chronic MSK pain.

Synaptic activity mediates information storage and memory consolidation in the brain and requires a fast de novo synthesis of mRNAs in the nucleus and proteins in synapses. Intracellular localization of a protein can be achieved by mRNA trafficking and localized translation. Activity-regulated cytoskeleton-associated protein (Arc) is a master regulator of synaptic plasticity and plays an important role in controlling large signaling networks implicated in learning, memory consolidation, and behavior. Transcription of the Arc gene may be induced by a short behavioral event, resulting in synaptic activation. Arc mRNA is exported into the cytoplasm and can be trafficked into the dendrite of an activated synapse where it is docked and translated. The structure of Arc is similar to the viral GAG (group-specific antigen) protein, and phylogenic analysis suggests that Arc may originate from the family of Ty3/Gypsy retrotransposons. Therefore, Arc might evolve through "domestication" of retroviruses. Arc can form a capsid-like structure that encapsulates a retrovirus-like sentence in the 3'-UTR (untranslated region) of Arc mRNA. Such complex can be loaded into extracellular vesicles and transported to other neurons or muscle cells carrying not only genetic information but also regulatory signals within neuronal networks. Therefore, Arc mRNA inter- and intramolecular trafficking is essential for the modulation of synaptic activity required for memory consolidation and cognitive functions. Recent studies with single-molecule imaging in live neurons confirmed and extended the role of Arc mRNA trafficking in synaptic plasticity.

The ratio between slower and faster frequencies of brain activity may change after stroke. However, few studies have used quantitative electroencephalography (qEEG) index of ratios between slower and faster frequencies such as the delta/alpha ratio (DAR) and the power ratio index (PRI; delta + theta/alpha + beta) for investigating the difference between the affected and unaffected hemisphere poststroke. Here, we proposed a new perspective for analyzing DAR and PRI within each hemisphere and investigated the motor impairment-related interhemispheric frequency oscillations. Forty-seven poststroke subjects and twelve healthy controls were included in the study. Severity of upper limb motor impairment was classified according to the Fugl-Meyer assessment in mild/moderate (n = 25) and severe (n = 22). The qEEG indexes (PRI and DAR) were computed for each hemisphere (intrahemispheric index) and for both hemispheres (cerebral index). Considering the cerebral index (DAR and PRI), our results showed a slowing in brain activity in poststroke patients when compared to healthy controls. Only the intrahemispheric PRI index was able to find significant interhemispheric differences of frequency oscillations. Despite being unable to detect interhemispheric differences, the DAR index seems to be more sensitive to detect motor impairment-related frequency oscillations. The intrahemispheric PRI index may provide insights into therapeutic approaches for interhemispheric asymmetry after stroke.

Objectives: The present study is aimed at investigating the frequency and associated factors of asymmetrical prominent veins (APV) in patients with acute ischemic stroke (AIS).

Methods: Consecutive patients with AIS admitted to the Comprehensive Stroke Center of Shanghai Fourth People's Hospital between January 2013 and December 2017 were enrolled. MRI including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and susceptibility-weighted imaging (SWI) was performed within 12 hours of symptom onset. The volume of asymmetrical prominent veins (APV) was evaluated using the Signal Processing In nuclear magnetic resonance software (SPIN, Detroit, Michigan, USA). Multivariate analysis was used to assess relationships between APV findings and medical history, clinical variables as well as cardio-metabolic indices.

Results: Seventy-six patients met the inclusion criteria. The frequency of APV ≥ 10 mL was 46.05% (35/76). Multivariate analyses showed that proximal artery stenosis or occlusion (≥50%) (P < 0.001, adjusted odds ratio (OR) = 660.0, 95%CI = 57.28-7604.88) and history of atrial fibrillation (P < 0.001, adjusted OR = 10.48, 95%CI = 1.78-61.68) were independent factors associated with high APV (≥10 mL).

Conclusion: Our findings suggest that the frequency of APV ≥ 10 mL is high in patients with AIS within 12 hours of symptom onset. History of atrial fibrillation and severe proximal artery stenosis or occlusion are strong predictors of high APV as calculated by SPIN on the SWI map.

Recent clinical practice has found that the spike-wave discharge (SWD) scopes of absence seizures change from small cortical region to large thalamocortical networks, which has also been proved by theoretical simulation. The best biophysics explanation is that there are interactions between coupled cortico-thalamic and thalamocortical circuits. To agree with experiment results and describe the phenomena better, we constructed a coupled thalamocortical model with bidirectional channel (CTMBC) to account for the causes of absence seizures which are connected by the principle of two-way communication of neural pathways. By adjusting the coupling strength of bidirectional pathways, the spike-wave discharges are reproduced. Regulatory mechanism for absence seizures is further applied to CTMBC via four different targeted therapy schemes, such as deep brain stimulation (DBS), charge-balanced biphasic pulse (CBBP), coordinated reset stimulation (CRS) 1 : 0, and (CRS) 3 : 2. The new CTMBC model shows that neurodiversity in bidirectional interactive channel could supply theory reference for the bidirectional communication mode of thalamocortical networks and the hypothesis validation of pathogenesis.

As a classical growth promoter and metabolic regulator, growth hormone (GH) is involved in development of the central nervous system (CNS). This hormone might also act as a neurotrophin, since GH is able to induce neuroprotection, neurite growth, and synaptogenesis during the repair process that occurs in response to neural injury. After an ischemic insult, the neural tissue activates endogenous neuroprotective mechanisms regulated by local neurotrophins that promote tissue recovery. In this work, we investigated the neuroprotective effects of GH in cultured hippocampal neurons exposed to hypoxia-ischemia injury and further reoxygenation. Hippocampal cell cultures obtained from chick embryos were incubated under oxygen-glucose deprivation (OGD, <5% O₂, 1 g/L glucose) conditions for 24 h and simultaneously treated with GH. Then, cells were either collected for analysis or submitted to reoxygenation and normal glucose incubation conditions (OGD/R) for another 24 h, in the presence of GH. Results showed that OGD injury significantly reduced cell survival, the number of cells, dendritic length, and number of neurites, whereas OGD/R stage restored most of those adverse effects. Also, OGD/R increased the mRNA expression of several synaptogenic markers (i.e., NRXN1, NRXN3, NLG1, and GAP43), as well as the growth hormone receptor (GHR). The expression of BDNF, IGF-1, and BMP4 mRNAs was augmented in response to OGD injury, and exposure to OGD/R returned it to normoxic control levels, while the expression of NT-3 increased in both conditions. The addition of GH (10 nM) to hippocampal cultures during OGD reduced apoptosis and induced a significant increase in cell survival, number of cells, and doublecortin immunoreactivity (DCX-IR), above that observed in the OGD/R stage. GH treatment also protected dendrites and neurites during OGD, inducing plastic changes reflected in an increase and complexity of their outgrowths during OGD/R. Furthermore, GH increased the expression of NRXN1, NRXN3, NLG1, and GAP43 after OGD injury. GH also increased the BDNF expression after OGD, but reduced it after OGD/R. Conversely, BMP4 was upregulated by GH after OGD/R. Overall, these results indicate that GH protective actions in the neural tissue may be explained by a synergic combination between its own effect and that of other local neurotrophins regulated by autocrine/paracrine mechanisms, which together accelerate the recovery of tissue damaged by hypoxia-ischemia.

Background: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear.

Methods: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier.

Results: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%.

Conclusion: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.