Translational Neuroscience最新文献

Background: Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoe^shl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoe^shl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoe^shl mice.

Results: Apoe^shl mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoe^shl mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test.

Conclusion: Our findings suggest the utility of Apoe^shl mice in investigating the function of ApoE in the central nervous system.

Objectives: Studies have shown that arterial spin labeling (ASL) effectively replaces traditional MRI perfusion imaging for detecting cerebral blood flow (CBF) in patients with Moyamoya angiopathy (MMA). However, there are few reports on the relationship between neovascularization and cerebral perfusion in patients with MMA. The aim of this study is to investigate the effects of neovascularization on cerebral perfusion with MMA after bypass surgery.

Methods: We selected patients with MMA in the Department of Neurosurgery between September 2019 and August 2021 and enrolled them based on the inclusion and exclusion criteria. ASL imaging was used to monitor the baseline CBF level before surgery and determine the changes in cerebral vessels at postoperative 1 week and 6 months, respectively. The Alberta stroke grade, modified Rankin Scale (mRS), and digital subtraction angiography images were used to evaluate the effect of postoperative CBF status and prognosis. Ninety hemispheres from 51 patients were included in this study. There were no significant differences in the baseline data of the enrolled patients. At 1 week and 6 months post-surgery, the CBF state in the operation area was significantly changed compared with that at baseline (P < 0.05). The preoperative Alberta score (t = 2.714, P = 0.013) and preoperative mRS score (t = 6.678, P < 0.001) correlated with postoperative neovascularization.

Conclusion: ASL is an effective method for detecting CBF and plays an important role in the long-term follow-up of patients with MMA. Combined cerebral revascularization significantly improves CBF in the operation area both in the short and long terms. Patients with lower preoperative Alberta scores and higher mRS scores were more likely to benefit from combined cerebral revascularization surgery. However, regardless of the type of patient, CBF reconstruction can effectively improve prognosis.

Background: Cohen syndrome (OMIM No. # 216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. Clinical manifestations include hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, and neutropenia. To date, more than 200 mutations of VPS13B have been reported in over 1,000 Cohen syndrome patients. This article reviews the clinical data of two cases of Cohen syndrome diagnosed by whole exome sequencing.

Results: Both children visited for psychomotor retardation. Gene detection showed a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and heterozygotic deletion of exon 3-19 of the VPS13B gene (Case 1), and a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and 8q22, NM_017890.4 Exon56 c10334_10335del in the VPS13B gene (Case 2). The variation was predicted to be pathogenic by related software, and they have not been reported.

Conclusion: Cohen syndrome should be considered in the differential diagnosis of any child with developmental retardation and neutropenia. The present study increases the mutation spectrum of the VPS13B gene and could be helpful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

Background: Baicalin has been shown to promote spatial learning and neural regeneration, which might increase the differentiation of neural stem cells in Alzheimer's disease (AD) rat models. We aimed to study the role of baicalin on neuronal pentraxin-1 (NPTX-1), neuronal pentraxin-2 (NPTX-2), and C-reactive protein (CRP) in AD model rats.

Methods: The 30 male Sprague Dawley rats were divided into three groups: the control group, the AD model group, and the AD + baicalin group. Then, the Morris water maze was used to verify the effect of baicalin on the memory and spatial learning of rats. Immunohistochemistry and immunofluorescence were used to observe the expression of NPTX-1, NPTX-2, and CRP in brain tissue.

Results: Compared with the AD model group, the AD rats treated with baicalin spent significantly less time finding escape latencies (P = 0.008) and had longer cross-platform times in the target quadrant (P = 0.015). In addition, the AD + baicalin group had significantly higher numbers of hippocampal neurons compared with the AD model group (P < 0.05). Baicalin also obviously decreased the apoptosis of neurons. Moreover, compared with the AD model group, the NPTX-1 and CRP expression in the AD + baicalin group was significantly reduced (P = 0.000) while the expression of NPTX-2 in the brain tissue of AD rats was significantly increased (P = 0.000).

Conclusions: Baicalin can play a therapeutic role by downregulating NPTX-1, upregulating NPTX-2, and downregulating CPR in AD model rats.

Approximately 6.8 million people die annually because of problems related to the central nervous system (CNS), and out of them, approximately 1 million people are affected by neurodegenerative diseases that include Alzheimer's disease, multiple sclerosis, epilepsy, and Parkinson's disease. CNS problems are a primary concern because of the complexity of the brain. There are various drugs available to treat CNS disorders and overcome problems with toxicity, specificity, and delivery. Barriers like the blood-brain barrier (BBB) are a challenge, as they do not allow therapeutic drugs to cross and reach their target. Researchers have been searching for ways to allow drugs to pass through the BBB and reach the target sites. These problems highlight the need of nanotechnology to alter or manipulate various processes at the cellular level to achieve the desired attributes. Due to their nanosize, nanoparticles are able to pass through the BBB and are an effective alternative to drug administration and other approaches. Nanotechnology has the potential to improve treatment and diagnostic techniques for CNS disorders and facilitate effective drug transfer. With the aid of nanoengineering, drugs could be modified to perform functions like transference across the BBB, altering signaling pathways, targeting specific cells, effective gene transfer, and promoting regeneration and preservation of nerve cells. The involvement of a nanocarrier framework inside the delivery of several neurotherapeutic agents used in the treatment of neurological diseases is reviewed in this study.

Many diseases affect the autonomous nervous system and the central nervous system simultaneously, for example Parkinson's disease or irritable bowel syndrome. To study neurophysiologic interactions between the intestinal electrical activity and the electroencephalography (EEG) pattern of the brain, we combined intestinal electrical stimulation (IES) and non-invasive telemetric full-band DC EEG recordings in an acute pig-model. Intestinal motility was monitored with accelerometers. Brain activity was analyzed with regard to network driven phenomena like phase amplitude coupling (PAC) within two time-windows: 1 min after IES (early response) and 3 min after stimulation (late response). Here we present the results for two stimulation sites (small intestine, colon) and two parietal scalp-EEG channels (right and left somatosensory cortex region). Electrical stimulation consisted of a 30 or 130 Hz pulse. In summary, the PAC modulation index at a parietal EEG recording position is decreased after IES. This effect is in line with an inhibitory effect of our IES protocol regarding peristalsis. The surprisingly strong effects of IES on network driven EEG patterns may be translated into new therapeutic techniques and/or diagnostic tools in the future. Furthermore, analytic tools, operating on sparse datasets, may be ideally suited for the integration in implantable intestinal pacemakers as feedback system.

[This retracts the article DOI: 10.1515/tnsci-2020-0109.].

Background a purpose: The collateral capacity of the circle of Willis (CoW) may play an important role in the development of ischemic strokes. The occurrence of classical polygon shows wide geographical variations and morphological data on diameters of the Willisian collaterals are scarce. We aimed to assess CoW variations and vessel diameters in a Central European cohort.

Subjects and methods: CoWs were removed during routine autopsy. The morphological pattern of the circles was recorded. The prepared circles were then put between two glass plates and tightly compressed. The length of the vessels and half of the circumference were measured under a light microscope enabling measurement with an approximation of 0.1 mm. Vessel diameters were calculated from vessel circumference.

Results: A total of 110 circles were analysed. Incomplete circles (missing one or two segments of CoW) were found in 25 cases (22.7%). Any forms of anatomical variations were detected in 14 cases (12.7%). When applying the <1 mm diameter threshold for analysis, 36 anterior communicating arteries (32.7%), 53 right posterior communicating arteries (48.2%), 73 left posterior communicating arteries (66.4%) and 18 posterior communicating arteries (16.3%) on both the sides were considered hypoplastic.

Conclusions: In patients without stroke in their history, complete CoW may be present in >60% of the cases. Our diameter data may serve as reference values for the Central-European population.

Background: Acacetin (5,7-dihydroxy-4'-methoxyflavone), one of the main extractions from Saussurea involucrata, has anti-inflammatory effects. Our previous study found that acacetin inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) signaling pathway after cerebral ischemia-reperfusion injury. NLRP3 inflammasome plays a role in Alzheimer's disease (AD) process. However, few studies have examined the effects of acacetin in AD.

Methods: We randomly divided APP swe/PS1dE9 double transgenic mice into acacetin group (intraperitoneal injection of 25 mg/kg acacetin) and AD model group (intraperitoneal injection of same volume of saline). C57BL/6 mice were selected as control group (same treatment with AD model group). After treating for 30 days, a Morris water maze test was conducted to evaluate spatial learning and memory of the mice. Senile plaque (SP) formation was evaluated by immunohistochemistry. NLRP3 inflammasome-related inflammatory factors and amyloid-β-42 were detected by Western blot or enzyme-linked immunosorbent assay.

Results: Acacetin improved spatial learning and memory of AD mice and reduced APP/β expression, thereby decreasing SP formation in the brain. Acacetin also reduced the expression of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), and interleukin-1β (IL-1β) and the release of inflammatory factors, tumor necrosis factor-α (TNF-α) and IL-1β.

Conclusions: Acacetin improved the learning and memory abilities of AD mice and exerted a protective effect on AD by inhibiting the NLRP3 signaling pathway and reducing SP formation.

N-Methyl-d-aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.