Journal of Neuroscience Research最新文献

Human induced pluripotent stem cells (hiPSCs), similar to embryonic stem cells, are a class of pluripotent stem cells with the potential to differentiate into various kinds of cells. Because the application of hiPSCs obtained by reprogramming patients' somatic cells in the treatment of brain diseases bypasses the ethical constraints on the use of embryonic stem cells and mitigates immune rejection, hiPSCs have profound clinical application prospects. In this review, we first summarized the differentiation methods of hiPSCs into different kinds of neurons, and secondly discussed the application of hiPSCs in several brain disease models, so as to provide a reference for the future application of hiPSCs in the studies and treatment of brain diseases.

Chronic stress is a common trigger of multiple neuropsychiatric illnesses. Animal models are widely used to study stress-induced brain disorders and their interplay with neuroinflammation and other neuroimmune processes. Here, we apply the prolonged 12-week chronic unpredictable stress (PCUS) model to examine rat behavioral and hippocampal transcriptomic responses to stress and to chronic 4-week treatment with a classical antidepressant fluoxetine, an anti-inflammatory agent eicosapentaenoic acid (EPA), a pro-inflammatory agent lipopolysaccharide and their combinations. Overall, PCUS evoked anxiety-like behavioral phenotype in rats, corrected by chronic fluoxetine (alone or combined with other drugs), and EPA. PCUS also evoked pronounced transcriptomic responses in rat hippocampi, involving > 200 differentially expressed genes. While pharmacological manipulations did not affect hippocampal gene expression markedly, Gpr6, Drd2 and Adora2a were downregulated in stressed rats treated with fluoxetine, EPA and fluoxetine + EPA, suggesting their respective protein products (G protein-coupled receptor 6, dopamine D2 receptor and adenosine A2A receptor) as potential evolutionarily conserved targets under chronic stress. Overall, these findings support the validity of rat PCUS paradigm as a useful model to study stress-related anxiety pathogenesis, and call for further research probing how various conventional and novel drugs may (co)modulate behavioral and neurotranscriptomic biomarkers of chronic stress.

Parkinson's disease (PD)-related depression is associated with aberrant neuronal oscillations and 5-hydroxytryptamine (5-HT) neurotransmission in the medial prefrontal cortex (mPFC). Intermittent theta-burst stimulation (iTBS), an updated pattern of high-frequency repetitive transcranial magnetic stimulation, has possible efficacy in PD-related depression. However, whether iTBS alleviates PD-related depression through modulating neuronal oscillations and 5-HT levels in the mPFC has not been determined. In this study, male Sprague–Dawley rats were used to establish a unilateral 6-hydroxydopamine-induced PD model. Then, acute iTBS was applied to the parkinsonian rats, and behavioral, neurochemical, and electrophysiological experiments were performed. We found that the parkinsonian rats exhibited increased immobility time and decreased sucrose preference accompanied by an increase of δ power and a decrease of θ power in the mPFC compared to sham-operated rats. One block of iTBS (1 block-iTBS, 300 stimuli) alleviated depressive-like behaviors in parkinsonian rats and elevated 5-HT levels in the mPFC compared to sham-iTBS. Additionally, it altered neuronal oscillations in the mPFC in the opposite fashion by suppressing the δ rhythm and enhancing the θ and β rhythms compared to sham-iTBS, suggesting that acute iTBS induces hyperactivity in the mPFC. With this iTBS paradigm, we also observed decreased parvalbumin expression in the mPFC, reflecting reduced cortical inhibition. Finally, correlation analyses showed strong correlation between immobility time and θ power after 1 block-iTBS. These findings suggest that the application of acute iTBS in parkinsonian rats produces antidepressant-like effects, which may be associated with elevated 5-HT levels and normalized neuronal oscillations in the mPFC.

In studying the neural correlates of working memory (WM) ability via functional magnetic resonance imaging (fMRI) in health and disease, it is relatively uncommon for investigators to report associations between brain activation and measures of task performance. Additionally, how the choice of WM task impacts observed activation–performance relationships is poorly understood. We sought to illustrate the impact of WM task on brain–behavior correlations using two large, publicly available datasets. We conducted between-participants analyses of task-based fMRI data from two publicly available datasets: The Human Connectome Project (HCP; n = 866) and the Queensland Twin Imaging (QTIM) Study (n = 459). Participants performed two distinct variations of the n-back WM task with different stimuli, timings, and response paradigms. Associations between brain activation ([2-back − 0-back] contrast) and task performance (2-back % correct) were investigated separately in each dataset, as well as across datasets, within the dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex, and whole cortex. Global patterns of activation to task were similar in both datasets. However, opposite associations between activation and task performance were observed in bilateral pre-supplementary motor area and left middle frontal gyrus. Within the dlPFC, HCP participants exhibited a significantly greater activation–performance relationship in bilateral middle frontal gyrus relative to QTIM Study participants. The observation of diverging activation–performance relationships between two large datasets performing variations of the n-back task serves as a critical reminder for investigators to exercise caution when selecting WM tasks and interpreting neural activation in response to a WM task.

The primary objective of this study was to examine neurological disorders and cognitive impairments in patients with secondary hypothyroidism and epilepsy undergoing treatment with antiepileptic medications. The study included 184 patients divided into three groups: Group 1 (subclinical hypothyroidism, n = 60), Group 2 (manifest hypothyroidism, n = 64), and Group 3 (control, n = 60). Patients in Group 2 received levothyroxine therapy (initial dose of 25 μg/day, titrated to 50–100 μg/day), while Groups 1 and 2 were treated with anti-seizure medications (valproic acid, 40 mg/kg/day). Neurological symptoms, including Babinski's reflex abnormalities (χ² = 8.15, p = 0.017) and sensory disturbances (χ² = 12.44, p = 0.005), were significantly more frequent in Group 2 than in Group 1. Cognitive test scores were significantly lower in Group 2 compared to Group 3 across all domains (F(2, 181) = 6.55, p = 0.002 for MMSE; F(2, 181) = 4.70, p = 0.010 for FAB; and F(2, 181) = 5.75, p = 0.006 for CDT), with Group 1 showing intermediate results. Regression analysis identified neurodegenerative disease risk (β = 0.34, CI: 0.20–0.48, p < 0.001), anemia (β = 0.32, CI: 0.15–0.49, p = 0.001), and prolonged stress (β = 0.26, CI: 0.12–0.40, p = 0.002) as significant predictors of cognitive decline, while higher education was protective (β = −0.28, CI: −0.42 to −0.14, p = 0.003). An inverse relationship was observed between TSH levels and cognitive scores (r = −0.55, p < 0.001).

Despite significant advancements in achieving high recanalization rates (80%–90%) for large vessel occlusions through mechanical thrombectomy, the issue of “futile recanalization” remains a major clinical challenge. Futile recanalization occurs when over half of patients fail to experience expected symptom improvement after vessel recanalization, often resulting in severe functional impairment or death. Traditionally, this phenomenon has been attributed to inadequate blood flow and reperfusion injury. More recently, ongoing neuronal death after reperfusion, which leads to the progression of the ischemic penumbra into the core infarct, has been termed “futile reperfusion.” This review explores the complex role of autophagy mechanisms in futile reperfusion following ischemic stroke, with a focus on its relationship to neuronal survival. We also examine the regulation of autophagic activity by epigenetic mechanisms. By investigating autophagy's role in ischemic stroke, we aim to identify novel pathways for precision treatment.

Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight the gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB axis forms a dynamic network facilitating bidirectional communication between the gastrointestinal tract, liver, and central nervous system. Dysregulation within this axis, encompassing gut dysbiosis and microbial metabolites, is emerging as a critical factor influencing PD progression. Our understanding of PD was traditionally centered on neurodegenerative processes within the brain. However, examining PD through the lens of the GLB axis provides new insights. This review provides a comprehensive analysis of microbial metabolites, such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), kynurenine, serotonin, bile acids, indoles, and dopamine, which are integral to PD pathogenesis by modulation of the GLB axis. Our extensive research included a comprehensive literature review and database searches utilizing resources such as gutMGene and gutMDisorder. These databases have been instrumental in identifying specific microbes and their metabolites, shedding light on the intricate relationship between the GLB axis and PD. This review consolidates existing knowledge and underscores the potential for targeted therapeutic interventions based on the GLB axis and its components, which offer new avenues for future PD research and treatment strategies. While the GLB axis is not a novel concept, this review is the first to focus specifically on its role in PD, highlighting the importance of integrating the liver and microbial metabolites as central players in the PD puzzle.