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2024, Volume 55 Issue 4
06 August 2024 Previous Issue   
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Review
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Technology and Methodology


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Review

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Myelin dynamics and its role in cognitive dysfunction in Alzheimer’s disease CHEN Jing-fei XIAO Lan 2024, 55 (4):  379-385.  doi: 10.16098/j.issn.0529-1356.2024.04.001 Abstract ( )   PDF (9757KB) ( )   Oligodendrocytes are myelin-forming cells of the central nervous system (CNS). The processes extending from each oligodendrocyte are capable of wrapping axon to form multiple myelin sheaths to ensure efficient and rapid conduction of action potentials along the axon. Recent studies have shown that myelin changes are quite active although most of the myelin sheaths in the adult brain are in a stable state. On the one hand, oligodendrocyte precursor cells continue to differentiate to form new myelin sheaths; on the other hand, a small portion of the formed myelin sheaths degenerate over time. Dynamic changes in myelin sheaths are thought to be a form of neural plasticity in the adult brain, which aims to regulate the function of neural circuits for adapting of new environments or acquiring new skills. In the brains with Alzheimer's disease (AD), myelin degeneration can lead to a compensatory increase in myelin regeneration, but it is still insufficient to compensate for the loss of myelin, and the promotion of new myelin formation is expected to be a new strategy to improve AD-related cognitive dysfunction. References | Related Articles | Metrics

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Research progress of the tertiary lymphoid structure in multiple sclerosis LIU Shuang MA Jian-mei 2024, 55 (4):  386-392.  doi: 10.16098/j.issn.0529-1356.2024.04.002 Abstract ( )   PDF (1741KB) ( )   Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system(CNS), which is characterized by infiltration of immune cells, glia activation, demyelination and neurodegeneration. With the progression of MS, the peripheric infiltrated immune cells promote lymphocytes to locate in parenchyma or meninges adjacent to active lesions by secreting cytokines, such as C-X-C motif chemokine ligand (CXCL)13, CXCL12 and tumor necrosis factor-α(TNF-α), contributing to the formation of tertiary lymphoid structure (TLS). TLS formation in the CNS can directly trigger immune reaction independent from peripheral immune system, leading to the differentiation of pathogenic lymphocytes, the activation of microglia and astrocyte, and the recruitment of additional peripheral immune cells into the CNS by secreting proinflammatory cytokines and chemokines. The immune reaction in CNS caused by TLS leads to aggravated neuroinflammation and pathological changes, even irreversible neuron damage, which is thought to be responsible the progression of MS. The formation, distribution, tissue structure, and the mechanism of formation and distribution of the TLS in MS are reviewed in this article, which may contribute to potential therapeutic approaches for chronic progressive MS.  References | Related Articles | Metrics

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Meningeal lymphatics: a gateway connecting the central nervous system to peripheral immune system FAN Rong LUO Yu-xiang GAO Zhi-hua 2024, 55 (4):  393-398.  doi: 10.16098/j.issn.0529-1356.2024.04.003 Abstract ( )   PDF (2847KB) ( )   Traditionally, the brain was considered as an immune-privileged organ. However, the re-discoveries of meningeal lymphatic vessels have revolutionized our understanding, revealing direct physical and functional connections between the central nervous system and the peripheral immunity. Meningeal lymphatic vessels play a crucial role in draining cerebro-spinal fluid, clearing metabolic waste from the brain, eliciting immune surveillance and maintaining immune homeostasis within the brain. They are implicated in the pathogenesis and progression of multiple central nervous system diseases. This review mainly focuses on the anatomical structure and physiological functions of meningeal lymphatic vessels, with brief introduction to their role in neurological diseases. We summarize recent research advances in meningeal lymphatic vessels, and provide insights for further research and clinical applications. References | Related Articles | Metrics

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Current progress on the role of central nervous system boarder-associated macrophages in brain homeostasis and diseases SHAO Chen-shuo WEI Li-hang TAN Guo-he 2024, 55 (4):  399-406.  doi: 10.16098/j.issn.0529-1356.2024.04.004 Abstract ( )   PDF (6069KB) ( )   An increasing number of studies have been focused on the field of immune system in the central nervous system（CNS），as the viewpoint of CNS immune privilege being challenged. Among them, CNS boarder-associated macrophages（BAMs）play a prominent role in the regulation of brain homeostasis and related diseases. Unlike microglia located in the brain parenchyma, BAMs are a type of specialized macrophages located in the meninges (including dura, arachnoid, and leptomeninges) ,perivascular spaces, and choroid plexus. They are crucial for immune surveillance, cerebrospinal fluid drainage, antigen clearance, material exchange, and etc. Here, we reviewed a series of relevant studies on the origin and roles of BAMs in CNS, so as to broaden the understanding of the mechanisms of by which BAMs maintain the brain homeostasis, as well as provide novel insights into the treatment of CNS diseases including Alzheimer 's disease. References | Related Articles | Metrics

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Correlation between inflammatory response in the neurovascular unit and autophagy after cerebral infarction TANG Li-na LU Zhi-cheng MO Sheng-long YANG Cheng-min JIAN Chong-dong SHANG Jing-wei 2024, 55 (4):  407-413.  doi: 10.16098/j.issn.0529-1356.2024.04.005 Abstract ( )   PDF (3063KB) ( )   With the improvement of China’s socioeconomic status, the issue of aging has become increasingly prominent, making cerebral infarction a common disease among the elderly. In recent years, research on cerebral infarction has gradually deepened, shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit, covering various aspects such as the blood-brain barrier, astrocytes, microglia, and autophagy. This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction, offering strong support for innovative future treatment strategies. In this review, we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction, emphasized the intricate interactions among these biological components, which might lay the groundwork for more effective managements and treatments of cerebral infarction. By comprehensively reviewing existing literatures, we proposed future research directions, aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.  References | Related Articles | Metrics

Research Articles

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Morphological features of the neural projection pathway from the dorsal raphe nucleus to the claustrum in mice GONG Tao CAI Zhi-ping SHI Juan LI Yun-qing 2024, 55 (4):  414-421.  doi: 10.16098/j.issn.0529-1356.2024.04.006 Abstract ( )   PDF (18403KB) ( )    Objective To explore the morphological features of the neural projection pathway from the dorsal raphe nucleus (DRN) to the claustrum (CLA) in mice.  Methods After injection of the retrograde tracer 594 retrobeads into the right CLA (n=3) or the anterograde tracer biotinylated dextran amine(BDA) into the DRN (n=3),  the distribution and the neurochemical feature of the retrogradely labeled neurons in the DRN, as well as the locations of nerve fibers and terminals throughout the brain and within the CLA, were observed by a combined immunofluorescent staining for 5-hydrozytryptamine(5-HT). The downstream target of the DRN-CLA projection was studied by injection of rabies retrograde monosynaptic virus (RV) into calcium ion/calmodulin dependent protein kinaeⅡ(CaMKⅡ)-Cre or glutamate decarboxylase 67(GAD67)-Cre mice. Results Retrograde labeled neurons were observed in the rostral, middle, and caudal segments of the DRN, with those in the middle segment and in the ventral part of the nucleus (DRV) the densest. Over 90% of the retrograde labeled neurons were 5-HT positive. After injection of BDA into the DRN, dense fiber projections were observed in the ventral tegmental area, parafascicular nucleus, ventral pallidum, and central amygdala nucleus. In comparison, DRN derived fibers and terminals in the CLA were relatively sparse. After injection of RV trans-synaptic virus into the CLA of CaMKⅡ-Cre and GAD67-Cre mice, respectively, dense RV-labeled presynaptic neurons were observed in the DRN of CaMKⅡ-Cre mice, while those in the DRN of GAD67-Cre mice were rather sparse.Conclusion The DRN-CLA projection pathway is characterized by the dense 5-HTergic neurons in the DRV, the relatively sparse fibers or terminals in the CLA, and a primary synaptic connection with CaMKⅡ positive neurons in the CLA.  References | Related Articles | Metrics

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Function and distribution of growth hormone receptor positive neurons in neonatal mouse brain XIA Yu REN Shu-yu LI Tao MEI Feng 2024, 55 (4):  422-429.  doi: 10.16098/j.issn.0529-1356.2024.04.007 Abstract ( )   PDF (21332KB) ( )   Objective To study the distribution and effect of growth hormone receptor (GHR) positive neurons in neonatal mouse brain Methods Six GHR-CreERT;mTOMATO/mGFP fluorescent reporter gene mice were selected. All of them were induced with tamoxifen on the 3rd day after birth. On the 10th and 17th days, 3 mice were sampled respectively at each time point. The distribution of GHR-positive neurons in the developing brain was observed at different stages. GHR floxed mice were generated. By crossing them with neuron-specific Thy1-CreERT;YFP mice, GHR was induced to be knocked out in neurons. Control mice (GHR fl/fl, 4 mice) and conditional knockout mice (Thy1-CreERT;YFP;GHR fl/fl, 4 mice) were induced on the 3rd day after birth. Samples were collected on the 10th day for observing the effect of neuronal GHR signaling on brain development. Results The GHR fluorescent reporter gene mice showed that GHR-positive cells are widely expressed in the developing mouse brain. GHR-positive neurons are concentrated in the paraventricular hypothalamic nucleus (PVN). After specifically knocking out GHR in neurons of the developing mouse brain, no significant differences were observed in the areal densities of neurons and various types of glial cells. Conclusion GHR-positive neurons are mainly concentrated in the PVN. Knocking out GHR in neurons of the developing brain cannot significantly change the morphology and density of various neural cell types. References | Related Articles | Metrics

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Effect of modulating the pathway from the medial prefrontal cortex to the thalamic paraventricular nucleus on pain transmission in mice ZHU Ke-hua WU Feng-ling SUN Han-xue HONG Jie CHEN Si-hai SHI Juan LI Yun-qing 2024, 55 (4):  430-436.  doi: 10.16098/j.issn.0529-1356.2024.04.008 Abstract ( )   PDF (5305KB) ( )   Objective  To explore the neuronal properties of the pathway from the medial prefrontal cortex (mPFC) to the paraventricular thalamic nucleus of (PVT) and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice. Methods  CTb was injected into the PVT of GAD67-GFP transgenic mice, and the properties of mPFC neurons projected to PVT were observed. The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain, such as mechanical pain, thermal pain, cold pain, and on capsaicin induced inflammatory pain. Results  CTB-labeled neurons in the mPFC were mainly distributed in layer V and layer VI, and were not double-labeled with GAD67-GFP. Chemogenetic activation of the mPFC-PVT pathway significantly decreased the mechanical pain threshold (p < 0.0001) and shortened the thermal pain latency (p < 0.001), but had no obvious effects on cold pain. Inhibition of this pathway significantly increased the mechanical pain threshold (p < 0.05). Activation of the pathway increased the paw licking time (p < 0.05) in acute inflammatory pain induced by intraplantar injection of capsaicin. Conclusion  mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain, thermal pain, and acute inflammatory pain in mice. References | Related Articles | Metrics

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Analysis of Human Brain Bank samples from Hebei Medical University DU Juan MI Shi-xiong JIN Yu-chuan YANG Qian MA Min ZHAO Xue-ru LIU Feng-cang ZHAO Chang-yi ZHANG Zhan-chi FAN Ping CUI Hui-xian 2024, 55 (4):  437-444.  doi: 10.16098/j.issn.0529-1356.2024.04.009 Abstract ( )   PDF (3786KB) ( )   Objective  To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research. Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed (from December 2019 to February 2024), including gender, age, cause of death, as well as quality control data such as postmortem delay time, pH value of cerebrospinal fluid and and RNA integrity number and result  of neuropathological diagnosis. Results  Until February 2024, 30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University, with a male to female ratio of 9∶1. Donors over 80 years old accounted for 53%. Cardiovascular and cerebrovascular diseases (36.67%) and nervous system diseases (23.33%) accounted for a high proportion of the death causes. The location of brain tissue donors in Shijiazhuang accounted for 90% donations, and the others were from outside the city. The postmortem delay time was relatively short, 90% within 12 hours and 10 % more than 12 hours. 69.23% of the brain samples had RNA integrity values greater than 6. Cerebrospinal fluid pH values ranged from 5.8 to 7.5, with an average value of 6.60 ± 0.45. Brain weights ranged from 906-1496g, with an average value of（1210.78 ± 197.84）g. Three apolipoprotein E (APOE) alleles were detected including five genotypes (ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4). Eleven staining methods related to neuropathological diagnosis had been established and used. A total of 12 cases were diagnosed as neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, corticobasal degeneration and progressive supranuclear palsy，etc.), accounting for 40% donated brains. The comorbidity rate of samples over 80 years old was 100%.  Conclusion  The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province, and it can also be more targeted to understand and identify potential donors. Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.  References | Related Articles | Metrics

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Effects of simulated extreme plateau environment on hippocampal transcriptome in rats FANG Xuan WAGN Tao CHENG Quan-cheng LIU Huai-cun ZHANG Yan NAN Yan CHEN Chun-hua ZHANG Wei-guang 2024, 55 (4):  445-451.  doi: 10.16098/j.issn.0529-1356.2024.04.010 Abstract ( )   PDF (2040KB) ( )   Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats.  Methods Healthy male SD rats aged 6-weeks, 200-250 g, were selected and divided into control group and plateau group. The control group was treated with normal pressure and oxygen (19 rats), and the plateau group was placed in a hypobaric hypoxia chamber (19 rats) at a simulated altitude of 8000 meters and treated for 72 hours. Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze (8 rats each). Three hippocampal tissues were extracted from each group for transcriptomic sequencing, and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG) and gene set enrichment analysis(GSEA) enrichment.  Results The behavioral result  showed that compared with the control group, the fear memory and spatial learning memory abilities of rats in plateau group were decreased. GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission, while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix.  Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus, destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment.    References | Related Articles | Metrics

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Effects of leptin on hypothalamic neuronal activity and adipose tissue metabolism in obese mice LIU Xiao-xuan ZHANG Han-si HAN Xiao-jing SHANG Xiao-di KANG Jing LIN Jun-tang YAN Xin QIAO Liang 2024, 55 (4):  452-459.  doi: 10.16098/j.issn.0529-1356.2024.04.011 Abstract ( )   PDF (5167KB) ( )   Objective  To investigate the effects of leptin on hypothalamic neuron activity and lipid metabolism in adipose tissue of obese mice. Methods 10 leptin-deficient obese (ob/ob) mice with homozygous mutation of leptin gene and 10 wild-type（WT）mice born in the same litter were randomly divided into control group and leptin treatment group. The activity of pro-opiomelanocortin(POMC) neurons and tyrosine hydroxylase(TH+) neurons, the morphological changes of adipose tissue and the expression of lipid-related genes were analyzed by immunofluorescent staining, HE staining and Real-time PCR. Results  Compared with the WT mice, the ob/ob mice showed decreased activity of POMC neurons and TH+ neurons and larger cell diameter in adipose tissue and liver tissue. In addition, the expressions of heat-related genes uncoupling protein 1(UCP1), cytochrome c oxidase subunit 8B(Cox8b) and cell death-inducing DNA fragmentation factor, alpha subunit-like effector A(Cidea) in subcutaneous white fat in ob/ob mice decreased significantly, and the expressions of lipid synthesis-related genes sterol regulatory element binding transcription factor 1(Srebp1) and fatty acid synthase(Fas) increased significantly. After treated with leptin, the activities of POMC and TH+ neurons were increased, and the cellular diameter and the degree of vacuolar degeneration were reduced in the adipose tissue and liver. Further analyses showed that the expressions of thermogenesis-related genes and lipolysis-related genes were increased, but expressions of lipid synthesis-related genes were reduced in brown adipose tissue. Conclusion  Leptin treatment could prevent the increasing of obesity in ob/ob mice, which is associated with increased lipolysis and reduced lipid synthesis through activation of hypothalamic POMC neurons and peripheral adipose tissue sympathetic nervous system References | Related Articles | Metrics

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MicroRNA-199a-5p reducing blood-brain barrier disruption following ischemic stroke in rats NI Guang-xiao DUAN Chun-qiao KOU Lu-lu MENG Ran WANG Xiao-qing WANG Pu 2024, 55 (4):  460-467.  doi: 10.16098/j.issn.0529-1356.2024.04.012 Abstract ( )   PDF (8149KB) ( )   Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB) integrity through PI3K/Akt pathway after cerebral ischemia. Methods  A permanent middle cerebral artery occlusion (MCAO) model was established in SPF adult male SD rats. Totally 48 rats were randomly divided into sham group (n=12), model group(n=12), MCAO+miR-199a-5p group(n=12), and MCAO+miR-199a-5p negative control group(n=12). The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats; The integrity of the BBB after ischemia stroke was detected through Evans blue staining; Immunofluorescent staining was used to determine apoptosis after cerebral ischemia; Western blotting technology was used to detect the protein expression of claudin-5, phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2), p-Akt, Akt, and vascular endothelial growth factor (VEGF)-A; Real-time PCR was used to investigate the expression levels of miR-199a-5p, claudin-5, and VEGF-A in the ischemic penumbra and infarcted area of the brain.  Results The result  showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats. MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke, activated the Akt signaling pathway, and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra. In addition, miR-199a-5p alleviated inflammation after cerebral ischemia. MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia. Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke, activate the Akt signaling pathway, reduce the expression of inflammatory cytokines, and alleviate the damage to the blood-brain barrier.  References | Related Articles | Metrics

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Hydroxylsafflor yellow A alleviating cerebral ischemia-reperfusion injury in rats by regulating cyclooxygenase-2/ prostaglandin E2 signaling pathway  YANG Ying-chun YANG Ying ZHANG Xiao-liang GAO Sai-hong JIANG Qing-liang LI Yu-feng JIA Shu-yu 2024, 55 (4):  468-474.  doi: 10.16098/j.issn.0529-1356.2024.04.013 Abstract ( )   PDF (9291KB) ( )   Objective To observe the effect of hyolroxylsafflor(HSYA) on cyclooxygenase-2(COX-2)/ prostaglandin E2(PGE2) signaling pathway, and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury（CIRI）. Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group), operation group(CIRI group), HSYA group and celecoxib group(C group), HSYA group subdivided into HSYA low dose group(HSYA-L group), HSYA medium dose group (HSYA-M group)and HSYA high dose group(HSYA-H group), 15 rats in each group. CIRI model was prepared by thread embolism method. The rats in each group were given intraperitoneal injection 30 minutes before operation. HSYA groups were given HSYA 10 mg/kg, 15 mg/kg, 25 mg/kg respectirely; C group was given celecoxib 40 mg/kg; S group and CIRI group were given the same amount of normal saline. Neurofunctional scores of each group of rats were performed immediately after recovery from modeling, cerebral infarction volume was measured 24 hours after reperfusion; At the same time, neuronal injury was observed by Nissl staining, the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting, and the changes of PGE2, tumor necrosis factor α(TNF-α) and interleukin(IL)-1β were detected by ELISA.   Results  Compared with the S group, in the CIRI group, neurofunctional scores increased dramatically (P<0.05), the volume of cerebral infarction increased dramatically (P<0.05), the damage of neurons increased and the number of neurons decreased dramatically (P<0.05), the expressions of COX-2 mRNA and protein increased dramatically (P<0.05), meanwhile the expressions of PGE2, TNF-α and IL-1β were also found dramatically increased (P<0.05); Compared with the CIRI group, in the HSYA group and C group, neurofunctional scores decreased dramatically (P<0.05), the volume of cerebral infarction was reduced dramatically (P<0.05), the damage of neurons decreased and the number of neurons increased dramatically (P<0.05), the expressions of COX-2 mRNA and protein, PGE2, TNF-α and IL-1β decreased dramatically(P<0.05). The differences between HSYA groups and both HSYA-L group and HSYA-M group compared with the C group were obvious(P<0.05), while no obvious differences were found in HSYA-H group compared with the C group(P>0.05). Conclusion  HSYA alleviates reperfusion injury in ischemic stroke may be related to the inhibition of COX-2/PGE2 signaling pathway.  References | Related Articles | Metrics

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Effects of conditional knockout ceruloplasmin in astrocytes on brain iron metabolism of mice LI Hai-yan LI Zhong-da HE Li-juan 2024, 55 (4):  475-481.  doi: 10.16098/j.issn.0529-1356.2024.04.014 Abstract ( )   PDF (5883KB) ( )   Objective To explore the mechanism of ceruloplasmin(CP) in brain iron metabolism. Methods  We obtained glial fibrillary acidic protein(GFAP)-cre-mediated ceruloplasmin knockout mice (CPGFAP cKO mice) by crossing CPflox/flox mice with transgenic GFAP-cre mice. Eighty-eight male mice aged 6 months were divided into four groups, WT, GFAP-cre, CPflox/flox and CPGFAP cKO. To observe whether astrocytic CP gene knockout specifically through genotype identification and immunofluorescent staining, and Western blotting method. The learning and memory function was detected by Morris water maze, brain iron levels in the cortex and hippocampus of mice were measured by inductively coupled plas mamass spectrometry(ICP-MS) and μ-probe X-ray fluorescence(μ-XRF), and iron contents in serum and liver were detected by iron kit. Results The mice of conditional knockout ceruloplasmin in astrocytes were obtained successfully by genotype identification, immunofluorescent staining and Western blotting method. The learning and memory ability was reduced in the water maze experiment, and iron contents decreased in the cortex and hippocampal regions of 6-month-old CPGFAP cKO group. While the level of serum iron and liver iron in the four groups did not change significantly. Conclusion The decline of learning and memory ability of mice with astrocytic CP gene knockout specifically is closely related to the decrease in brain iron. The main function of CP may be to help brain cells to absorb iron. References | Related Articles | Metrics

Technology and Methodology

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Differential expression analysis of the transcriptome for human basal ganglia from normal donors and Parkinson’s disease patients ZU Gao-yu LI Feng-jiao XIAN Wei-wei GUO Yang-yang ZHAO Bai-cheng LI Wen-sheng YOU Lin-ya 2024, 55 (4):  482-492.  doi: 10.16098/j.issn.0529-1356.2024.04.015 Abstract ( )   PDF (4993KB) ( )   Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes (DEGs) among different nuclei, gender, and Parkinson’s disease (PD), followed by the biological function annotations of the DEGs. Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups, and the control group was further categorized into female and male groups. RNA from each sample was extracted for high-throughput transcriptome sequencing. Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group, nuclei-specific, gender-specific, and PD-specific DEGs, followed by gene enrichment analysis and functional annotation. Results Sequencing analysis revealed top DEGs such as DRD1, FOXG1, and FAM183A in the caudate; SLC6A3, EN1, SLC18A2, and TH in the substantia nigra; MEPE and FGF10 in the globus pallidus; and SLC17A6, PMCH, and SHOX2 in the subthalamic nucleus. In them, putamen showed some overlapping DEGs with caudate, such as DRD1 and FOXG1. A significant number of DEGs were identified among different nuclei in the control group, with the highest number between caudate and globus pallidus (9321), followed by putamen and globus pallidus (6341), caudate and substantia nigra (6054), and substantia nigra and subthalamic nucleus (44). Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration. Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential, while downregulated DEGs were enriched in myelination and cell adhesion. Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction, while downregulated DEGs were enriched in myelination of neurons. Totally 468, 548, 1402, 333, and 341 gender-specific upregulated DEGs and 756, 988, 2532, 444, and 1372 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission. At last, 709, 852, 276, 507, and 416 PD-specific upregulated DEGs and 830, 2014, 1218, 836, and 1730 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation. Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei, as well as DEGs among different nuclei, different gender, and between control and PD. References | Related Articles | Metrics

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Analysis of cerebral blood flow perfusion in newly diagnosed early-onset depression using 3D pseudo-continuous arterial spin labeling MRI SUN Chen-xi LIU Tian-ci YIN Chang-qing LIU Shu-wei 2024, 55 (4):  493-500.  doi: 10.16098/j.issn.0529-1356.2024.04.016 Abstract ( )   PDF (7083KB) ( )   Objective To analyze the cerebral blood flow changes in patients with newly diagnosed untreated early-onset depression (EOD), using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL), and to explore its relationship with clinical phenotypes. Methods The Hamilton Depression Scale (HAMD), Childhood Trauma Questionnaire (CTQ) scores, 3D T1WI, and 3D-pCASL brain images of 65 untreated EOD patients and 55 healthy volunteers(HC group) were collected. SPM 12 and DPABI_V7.0 software were used to preprocess and analyze the whole brain images in two groups. Xjview software was used to analyze the value of cerebral blood flow (CBF) at the whole brain level of the two groups, and SPSS 25.0 software was used to evaluate the correlation of CBF values with HAMD scores and CTQ scores. Results Compared with the HC group, the CBF of the EOD group was reduced significantly［P<0.05,  cluster size>50, false discovery rate(FDR) correction］ in the right opercular inferior frontal gyrus (t=5.89), right temporo-parieto-occipital (TPO) region (t=6.49), and blood perfusion increased significantly (P<0.05, cluster size>50, FDR correction) in the left superior frontal gyrus (t=5.31) and left insular lobe (t=4.70). Conclusion The proportion of EOD patients with childhood trauma experience is relatively large. EOD patients have both reduced areas and increased areas in cerebral perfusion. The CBF value of the right TPO area is negatively correlated with HAMD scores; The CBF value of the left superior frontal gyrus is positively correlated with the total score of CTQ and the index of physical neglect score in CTQ, which is different from the result  of studies that do not distinguish between early-onset and late-onset depression.    References | Related Articles | Metrics

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Changes in diffusion tensor image analysis along the perivascular space index during aging HUANG Chen-ye LI Xiang-jun XIE Dao-jun 2024, 55 (4):  501-507.  doi: 10.16098/j.issn.0529-1356.2024.04.017 Abstract ( )   PDF (2808KB) ( )   Objective To calculate the diffusion tensor image analysis along the perivascular space(DTI-ALPS) index, evaluate the function of the glymphatic system, observe the changes in the DTI-ALPS index during the aging process, and find the relationship between the DTI-ALPS index and correlates of certain executive functions that reflect mental flexibility, based on DTI-ALPS. Methods The FSL toolbox was used to extract the DTI-ALPS index of the dominant hemisphere of the brain of adult subjects in the NKI Rockland Sample data set, and the correlations between the DTI-ALPS index and age and design fluency practical accuracy were analyzed, respectively. Differences in DTI-ALPS index among different age groups and the mediating effect of DTI-ALPS index between age and design fluency practical accuracy were analyzed. Results The DTI-ALPS index was negatively correlated with age (r=-0.288, P<0.001), but there was a local peak of recovery in the 60-69 age group (P<0.01).The DTI-ALPS index was positively correlated with the design fluency practical accuracy (r=0.258, P=0.001).The mediating effect of DTI-ALPS index between age and design fluency practical accuracy was statistically significant (P<0.05), and the mediating effect accounted for 22.1% of the total effect. Conclusion  The DTI-ALPS index showed an overall downward trend during the aging process, but there is a local peak of recovery in the 60-69 age group. At the same time, the DTI-ALPS index might be related to certain executive functions that could reflect thinking flexibility.  References | Related Articles | Metrics

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Differences in robustness of brain structure covariance networks among individuals with different circadian rhythm preferences HUANG Chen-ye, LI Xiang-jun, XIE Dao-jun 2024, 55 (4):  508-514.  doi: 10.16098/j.issn.0529-1356.2024.04.018 Abstract ( )   PDF (5538KB) ( )   Objective  To explore the differences in the robustness of structural covariance networks among populations with different circadian rhythm preferences, and to constructing brain structural covariance networks based on gray matter volume and cortical thickness. Methods  Morphological metrics of gray matter from early chronotype and late chronotype volunteers was extracted by using the CAT12 toolbox. Structural covariance networks based on gray matter volume and cortical thickness were constructed according to the LPBA40 atlas and Desikan-Killiany atlas. Graph theoretical parameters were calculated and the resilience of structural covariance networks against deliberate attacks were assessed by utilizing the GAT toolbox to observe the network’s robustness. Results  In the structural covariance network constructed based on gray matter volume, when using betweenness centrality as the target of deliberate attacks and network size as the measure of network robustness, the structural covariance network of early chronotype volunteers exhibits greater robustness than that of late chronotype volunteers (P<0.05).When using node degree as the target of deliberate attacks and network size as the evaluation metric for network robustness, the structural covariance network robustness of early chronotype volunteers showed no statistically significant difference compared with the late chronotype volunteers (P>0.05).In the structural covariance network constructed based on cortical thickness, when using betweenness centrality or node degree as the targets of deliberate attacks, and network size as the evaluation metric for network robustness, the structural covariance network robustness of early chronotype volunteers was weaker than that of late chronotype volunteers (P<0.05). Conclusion  The covariance relationships among brain gray matter morphology vary among populations with different circadian rhythm preferences, and the differences in structural covariance network robustness may be one of the manifestations, which provides a new understanding of the neuroanatomical features related to circadian rhythm. References | Related Articles | Metrics