An overview of systematic reviews of acupuncture for neurodegenerative disease.

BACKGROUND: Acupuncture has been widely used in the treatment of neurodegenerative diseases and a large number of systematic reviews (SRs) have been published, but the results are controversial. Therefore, it is necessary to comprehensively summarize and objectively evaluate the clinical evidence of acupuncture for neurodegenerative diseases. OBJECTIVE: To evaluate the SRs that assess the efficacy and safety of acupuncture for neurodegenerative diseases. This overview is intended to provide evidence for clinical decision making by healthcare providers and policymakers and to provide evidence for clinical decision making by healthcare providers and policymakers and to provide recommendations for researchers to conduct high quality SRs and clinical studies. METHODS: We searched four Chinese databases (SinoMed, CNKI, Wanfang and VIP) and four international databases (Cochrane Library, Embase, PubMed and Web of Science) for SRs of acupuncture for neurodegenerative diseases. The search period ran from the beginning of the database to March 5, 2023. Literature screening and data extraction were performed independently by two individuals. Methodological quality, risk of bias and associated evidence levels were assessed for all SRs using AMSTER 2, ROBIS and GRADE tools. In addition, the RCT overlap between SRs was calculated by corrected coverage area (CCA). We also conducted quantitative synthesis or descriptive analysis of the relevant data. RESULTS: Finally, we identified 53 SRs (three were qualitative descriptions and fifty were meta-analyses). Under AMSTAR 2, only one SR was rated as moderate quality, six SRs as low quality and 46 SRs as very low quality. According to ROBIS, 33 SRs were rated as a high risk of bias and 20 as a low risk of bias. Cognitive functions in neurodegenerative diseases, activities of daily living and the motor and non-motor outcomes associated with PD were included to summary description. The pooled results show that acupuncture combined with conventional treatment may have an overall advantage over conventional treatment, but the quality of evidence is low. Specific adverse reactions/events were reported in 20 SRs. Common needle-related adverse events included pain, dizziness, bleeding, or subcutaneous hematoma. No severe adverse events were reported in any SRs. CONCLUSION: Evidence suggests that acupuncture is generally effective and relatively safe for cognitive function and activities of daily living in neurodegenerative diseases. In addition, acupuncture may have some benefits in improving motor and non-motor symptoms in patients with PD. However, high-quality RCTs and SRs are still needed to further clarify the efficacy and safety of acupuncture in treating neurodegenerative diseases.

Comprehensive review on gene mutations contributing to dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the most common primary myocardial diseases. However, to this day, it remains an enigmatic cardiovascular disease (CVD) characterized by ventricular dilatation, which leads to myocardial contractile dysfunction. It is the most common cause of chronic congestive heart failure and the most frequent indication for heart transplantation in young individuals. Genetics and various other factors play significant roles in the progression of dilated cardiomyopathy, and variants in more than 50 genes have been associated with the disease. However, the etiology of a large number of cases remains elusive. Numerous studies have been conducted on the genetic causes of dilated cardiomyopathy. These genetic studies suggest that mutations in genes for fibronectin, cytoskeletal proteins, and myosin in cardiomyocytes play a key role in the development of DCM. In this review, we provide a comprehensive description of the genetic basis, mechanisms, and research advances in genes that have been strongly associated with DCM based on evidence-based medicine. We also emphasize the important role of gene sequencing in therapy for potential early diagnosis and improved clinical management of DCM.

Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.

Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SKCA/IKCA expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.

Integrated SOAs enable energy-efficient intra-data center coherent links.

Coherent optical links are becoming increasingly attractive for intra-data center applications as data rates scale. Realizing the era of high-volume short-reach coherent links will require substantial improvements in transceiver cost and power efficiency, necessitating a reassessment of conventional architectures best-suited for longer-reach links and a review of assumptions for shorter-reach implementations. In this work, we analyze the impact of integrated semiconductor optical amplifiers (SOAs) on link performance and power consumption, and describe the optimal design spaces for low-cost and energy-efficient coherent links. Placing SOAs after the modulator provide the most energy-efficient link budget improvement, up to 6 pJ/bit for large link budgets, despite any penalties from nonlinear impairments. Increased robustness to SOA nonlinearities makes QPSK-based coherent links especially attractive, and larger supported link budgets enable the inclusion of optical switches, which could revolutionize data center networks and improve overall energy efficiency.

Acupuncture and moxibustion in patients with cancer-related insomnia: A systematic review and network meta-analysis.

Objectives: Cancer-related insomnia (CRI) is one of the most common and serious symptoms in patients with cancer. Acupuncture and moxibustion have been widely applied in the treatment of CRI. Nevertheless, the comparative efficacy and safety of different acupuncture and moxibustion techniques remain unclear. This study aimed to evaluate and compare the efficacy and safety of different acupuncture and moxibustion techniques in the treatment of CRI. Methods: Eight medical databases were comprehensively searched for relevant randomized controlled trials (RCTs) as of June 2022. Two independent reviewers assessed the risk of bias and conducted the research selection, data extraction, and quality assessment of the included RCTs. A network meta-analysis (NMA) was performed using frequency models, combining all available direct and indirect evidence from RCTs. The Pittsburgh Sleep Quality Index (PSQI) was set as the primary outcome, and adverse events and effective rates were set as the secondary outcomes. The efficacy rate was calculated as the ratio of patients with insomnia symptom relief to the total number of patients. Results: Thirty-one RCTs with 3,046 participants were included, including 16 acupuncture- and moxibustion-related therapies. Transcutaneous electrical acupoint stimulation [surface under the cumulative ranking curve (SUCRA) 85.7%] and acupuncture and moxibustion (SUCRA 79.1%) were more effective than Western medicine, routine care, and placebo-sham acupuncture. Furthermore, Western medicine showed significantly better effects than placebo-sham acupuncture. In the NMA, the acupuncture and moxibustion treatments with the best therapeutic effects for CRI were transcutaneous electrical acupoint stimulation (SUCRA 85.7%), acupuncture and moxibustion (SUCRA 79.1%), auricular acupuncture (SUCRA 62.9%), routine care combined with intradermal needling (SUCRA 55.0%), and intradermal needling alone (SUCRA 53.3%). No serious acupuncture- or moxibustion-related adverse events were reported in the included studies. Conclusion: Acupuncture and moxibustion are effective and relatively safe in treating CRI. The relatively conservative recommended order of acupuncture- and moxibustion-related therapies for CRI is as follows: transcutaneous electrical acupoint stimulation, acupuncture and moxibustion, and auricular acupuncture. However, the methodological quality of the included studies was generally poor, and further high-quality RCTs are needed to strengthen the evidence base.

Dose-effect relationship of different acupuncture courses on chronic insomnia disorder: study protocol for a randomized controlled trial.

Background: Chronic insomnia disorder (CID) is increasing in prevalence year by year, is long lasting, and potentially risky. Acupuncture has been widely used in the clinical management of this condition. However, there is still a lack of direct evidence on the dose-effect relationship between different acupuncture courses and clinical efficacy. To identify this relationship, we will design a randomized controlled trial to clarify the difference in efficacy of different acupuncture courses for CID. Methods and design: This is a prospective, parallel, single center randomized controlled trial. Two hundred and one participants with CID will be randomly divided into three groups (Group A, Group B, and Group C). The three groups will be given acupuncture therapy for 4, 6, and 8 weeks, three sessions per week, with at least 1 day between sessions. Follow-up will continue until the third month after the end of treatment. The primary outcome is the Insomnia Severity Index (ISI), and secondary outcomes include percentage of ISI < 8 points, the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Fatigue Severity Scale (FSS), medication use, and safety. Discussion: This study is expected to provide direct evidence for the optimal treatment cycle of acupuncture for CID, as well as to facilitate health economic evaluation. Clinical trial registration: https://clinicaltrials.gov/, identifier [ChiCTR2300073711].

A case report and review of literature: Tuberculous pericarditis with pericardial effusion as the only clinical manifestation.

Tuberculosis is a main cause of pericardial disease in developing countries. However, in patients with atypical clinical presentation, it can lead to misdiagnosis, missed diagnosis, and delayed treatment. In this study, we report a case of a 61-year-old woman admitted to the cardiac intensive care unit with "weakness and loss of appetite" and a large pericardial effusion shown by echocardiography. After hospitalization, a pericardiocentesis was performed, and the pericardial fluid was hemorrhagic. However, the Xpert MTB/RIF and T-SPOT tests were negative, and repeated phlegm antacid smears and culture of pericardial fluid did not reveal antacid bacilli. The patient eventually underwent thoracoscopic pericardial biopsy, which revealed extensive inflammatory cells and significant granulomas. Combined with the fact that the patient's pericardial effusion was exudate, the patient was considered to be suspected of tuberculous pericarditis (TBP) and given empirical anti-tuberculosis treatment the patient's symptoms improved and the final diagnosis was TBP. In this case report, it is further shown that a negative laboratory test cannot exclude tuberculosis infection. In recurrent unexplained pericardial effusions, the pericardial biopsy is feasible. In countries with a high burden of tuberculosis, empirical antituberculosis therapy may be used to treat the pericardial effusion that excludes other possible factors.

The Clinical Effect of Blue Light Therapy on Patients with Delayed Sleep-Wake Phase Disorder.

OBJECTIVE: To investigate the feasibility and patient acceptance of applying blue light glasses to treat delayed sleep-wake phase disorder (DSWPD). METHODS: Fifteen patients with DSWPD were collected as the observation group and 15 healthy people as the control group. The patients wore blue light glasses with a continuous radiation wavelength of about 470 nm for 1h to 2h during the period from 06:30 to 09:00 in the morning after waking up, respectively. Assessment of Hamilton Anxiety Scale 14 items (HAMA14), Hamilton Depression Rating Scale 24 items (HAMD24), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Morningness-Eveningness Questionnaire (MEQ), and Insomnia Severity Index (ISI) scores before and after 1 week of treatment. Pearson correlation was used to analyze the correlation between the efficacy of patients with sleep-wake phase delay disorder and HAMA14, HAMD24, PSQI, ISI, ESS, MEQ, SL (sleep time), TST (total sleep time), TTiB (total time in bed), SQ (sleep quality), TOA (total arousal time), WASO (wake after sleep onset), AAT (average arousal time), and SE (sleep efficiency percent). Multi-factor logistic regression analysis of factors influencing the efficacy of patients with sleep-wake phase delay disorder. RESULTS: After treatment, PSQI-G scores, number of nighttime awakenings and time of awakening recorded in the sleep diary decreased significantly in the observation group (P < 0.05), and subjective sleep quality and MEQ scores increased (P < 0.05). MEQ score shifted from "moderate night type" to "intermediate type", sleep-wake phase tended to shift forward. The total PSQI score and Pittsburgh Sleep Quality Index Global (PSQI-G) score were significantly lower in the control group after treatment (P < 0.05). By Pearson correlation analysis, the efficacy of patients with sleep-wake phase delay disorder was significantly correlated with HAMA14, HAMD24, PSQI, ISI, ESS, MEQ, SL, TST, TTiB, SQ, TOA, WASO, AAT, and SE. Multifactorial logistic regression analysis revealed that the factors influencing the efficacy of patients with sleep-wake phase delay disorder were PSQI, ISI, ESS, MEQ, SL, TST, TTiB, SQ, TOA, WASO, AAT, and SE. CONCLUSION: Blue light therapy has a positive effect on improving subjective sleep quality, reducing the number of nocturnal awakenings and the duration of nocturnal awakenings, improving daytime function, and shifting the sleep phase forward in patients with DSWPD. Blue light therapy improves subjective sleep quality and daytime function the following day in normal individuals.

A Review of Prognosis Model Associated With Cardiogenic Shock After Acute Myocardial Infarction.

Objective: Cardiogenic shock seriously affects the survival rate of patients. However, few prognostic models are concerned with the score of cardiogenic shock, and few clinical studies have validated it. In order to optimize the diagnosis and treatment of myocardial infarction complicated with cardiogenic shock and facilitate the classification of clinical trials, the prognosis score model is urgently needed. Methods: Cardiogenic shock, severe case, prognosis score, myocardial infarction and external verification were used as the search terms to search PubMed, Embase, Web of Science, Cochrane, EBSCO (Medline), Scopus, BMC, NCBI, Oxford Academy, Science Direct, and other databases for pertinent studies published up until 1 August 2021. There are no restrictions on publication status and start date. Filter headlines and abstracts to find articles that may be relevant. The list of references for major studies was reviewed to obtain more references. Results and Conclusions: The existing related models are in urgent need of more external clinical verifications. In the meanwhile, with the development of molecular omics and the clinical need for optimal treatment of CS, it is urgent to establish a prognosis model with higher differentiation and coincidence rates.

Hemophagocytic Lymphohistiocytosis Associated to Klebsiella pneumoniae Infection: A Case Report.

This is a case analysis of a 73-year-old Chinese man admitted to the cardiac intensive care unit (ICU) with fever and general pain. Based on the patient's initial condition of multi-organ function impairment and increased serum ferritin, and after a series of examinations, the patient was diagnosed with Klebsiella pneumonia-induced hemophagocytic lymphohistiocytosis (HLH). Meropenem and dexamethasone were used in combination to treat the patient, and the results were very successful. In this case report, it is further suggested that Klebsiella pneumoniae is a possible trigger of HLH, and a combination of antibiotics and corticosteroids can be effective in treating HLH. It is also recommended that doctors in the ICU of each department should pay attention to the role of hyperferritinemia in the diagnosis of HLH, and ICU admission teams should include ferritin in their monitoring.

Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model.

OBJECTIVE: Astragalus polysaccharides (APS) are active constituents of Astragalus membranaceus. In this study, we aimed to investigate the effects of APS on memory impairment in a diabetic rat model and their mechanisms. METHODS: A diabetic model was established in 50 male Wistar rats with streptozotocin intra-peritoneal injection. A blood glucose level higher than 16.7 mmol/L obtained 72 hours after the injection was regarded as a successful diabetic model. The modeled rats were divided into model group, high, medium, and low doses of APS, and piracetam groups (positive control). A group of ten rats without streptozotocin-induced diabetes were used as a normal control. After respective consecutive 8-week treatments, the levels of blood fasting plasma glucose, insulin, hemoglobin A1c, memory performance, hippocampal malondialdehyde, and superoxide dismutase were determined. RESULTS: After the 8-week APS treatment, serum fasting plasma glucose, hemoglobin A1c, and insulin levels were decreased compared with those of the model group (P<0.05). Importantly, memory impairment in the diabetic model was reversed by APS treatments. In addition, hippocampal malondialdehyde concentration was lowered, whereas that of superoxide dismutase was higher after APS treatments. CONCLUSION: APS are important active components responsible for memory improvement in rats with streptozotocin-induced diabetes. The potential mechanism of action is associated with the effects of APS on glucose and lipid metabolism, and antioxidative and insulin resistance. APS are constituents of A. membranaceus that are potential candidate therapeutic agents for the treatment of memory deficit in diabetes.

Early postnatal repeated maternal deprivation causes a transient increase in OMpg and BDNF in rat cerebellum suggesting precocious myelination.

Repetitive maternal deprivation (MD) of neonatal rats during early life is known as one of the strongest stressors to pre-weaned animals. There is increasing evidence that the cerebellum is involved in cognition and emotion. In the present study, we examined how neurotrophic factors and myelin-associated molecules and their receptors (NGF, BDNF, OMgp, TrkA, TrkB, p75 NTR, and NgR) in the cerebellum are affected by early postnatal maternal separation. Rat pups were separated from their mothers for 3h/day during postnatal days (PND) 10-15. At PND 16 and 30, the levels of mRNA and protein in the cerebellum were determined using real-time PCR and Western blot analysis. Cerebellar mRNA and protein levels of BDNF, TrkB, and OMgp were significantly increased in MD rats at PND 16. However, by PND 30 these variables normalized to control levels. In contrast, the levels of mRNA and protein for NGF, TrkA, p75 NTR, and NgR were unchanged at both ages examined. Transient enhancement of neurotrophic system and myelin-associated molecule expression may cause interference of normal development of the cerebellum such as precocious myelination, which may lead to functional and cognitive deficits later in life.

Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.

Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.

Prolonged maternal separation disturbs the serotonergic system during early brain development.

Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5-hydroxyindoleacetic acid and using real-time RT-PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5-hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real-time RT-PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life.

Early postnatal maternal separation causes alterations in the expression of ß3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity.

The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague-Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3h each day during the 10-15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), ß3-adrenergic receptor (ß3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through ß3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the ß3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

Secretion-related structures of hypothalamo-hypophysial terminals in the rat posterior pituitary.

Hypothalamic terminals were investigated in the rat posterior pituitary (PP). Injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) and co-injection of WGA-HRP with Rab3A-siRNA were made into the hypothalamus, respectively. Additional injection of WGA-HRP was made into the hypothalamus in the animals exposed to ethanol. These injections resulted in heavy labeling of fibers exclusively confined to the PP. Ultrastructural observations showed terminals, fibers, pituicytes, capillaries and vascular spaces in the PP. Although the majority of terminals were observed to contain large dense core vesicles (LDCVs) and HRP-reaction products (HRP-RPs), exocytosis of LDCVs in close proximity to cell membrane was not found. Interestingly, a few terminals showed alteration of cell membrane called "apocrine-like structure" containing LDCV and RP. The narrow neck portion of the structure gave the appearance that it may have been in some stage of separating from terminals. Other remarkable feature was that terminals occasionally reveal the structure of "leakage" of RP discharged into vascular spaces crossing cell membrane. Such hormone-releasing mechanism might be involved in one of "diacrine-like secretion". In the present study secretion-related structures of hypothalamic terminals in the PP are quite different from normal vesicular exocytosis.

Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex.

This study was conducted in order to examine the effects of early postnatal maternal separation stress on the age-dependent fluctuations in the expression levels of neurotrophic factor ligands and receptors in the developing cerebellum. Wistar rats were separated from their mothers for 3 h each day during postnatal days (PND) 10 to 15. The expression level of mRNA for brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), insulin-like growth factor-1 (IGF-1), and type-1 IGF receptor (IGF-1R) were evaluated in the cerebellum on PND16, 20, 30, and 60 with real-time RT-PCR. The mRNA levels of cerebellar BDNF in maternally separated rats were increased on PND16, while the other variables showed no significant alterations at any of the time points examined. However, the effects of an identical maternal separation on the cerebral cortex were previously reported to be completely different. These results indicate regional differences in the responses of neurotrophic factor ligands/receptors between the cerebellum and cerebral cortex. Given that neurotrophic factors play important roles in brain development, alterations in these factors may interrupt normal brain development and ultimately, lead to functional disruptions.

Morphological evidence of an altered process of synaptic transcytosis in adult rats exposed to ethanol.

AIMS: The effects of ethanol exposure on synaptic structure were investigated in the nucleus of solitary tract (NST) in rats, using the horse-radish peroxidase (HRP) method. METHODS: Eight-week-old experimental rats were allowed free access to a liquid diet containing ethanol for 3 weeks, while controls were given an isocaloric diet. Some of the control and experimental animals were given an injection of wheat germ agglutinin conjugated with HRP (WGA-HRP) into the vagus nerve toward the end of the treatment period. After the treatment, the neuropil region of the NST was examined under an electron microscope. RESULTS: We observed that a few terminals were characterized by deep indentation of axodendritic membranes into the post-synaptic neurons. This appeared to be similar to that commonly seen in exocrine glands. Interestingly, the indented portion often contained various sizes of vacuoles and flattened cisternae. HRP-reaction product (RP) transported to terminals was recognized easily as an electron-dense lysosomal substance when lead citrate staining was omitted. Terminals containing HRP-RP also revealed quite a similar structure with indentation of axodendritic membranes as described earlier. The results are considered to confirm that terminals forming 'apocrine-like structures' observed in the ethanol-fed animals with no injection of WGA-HRP originate from afferent fibers of the vagus nerve. CONCLUSION: The present study suggests the possibility that the alteration of the synaptic structure induced by ethanol exposure can lead to the neuronal transcytosis of materials including proteins which is different from the normal vesicular exocytosis involved in chemical synaptic transmission.

Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats.

AIMS: This study was carried out to examine the effects of early postnatal maternal separation stress on the development of the cerebral cortex with respect to time-dependent fluctuations of neurotrophic factor ligand and receptor expression. MAIN METHODS: Wistar rats were separated from their mothers for 3h per day during postnatal days (PND) 10 to 15. The cerebral cortex was analyzed by real-time RT-PCR for the evaluation of the expression of mRNA for brain-derived neurotrophic factor (BDNF), TrkB, insulin-like growth factor-1 (IGF-1), and type 1 IGF receptor (IGF-1R) on PND16, 20, 30, and 60. KEY FINDINGS: The expression of these neurotrophic factor ligands and receptors in the cerebral cortex was enhanced on PND16 and PND20, and then it returned to baseline levels on PND30. By PND60, however, the expression levels were attenuated. SIGNIFICANCE: The important implication of this study is the persistent abnormal fluctuation of neurotrophic factor expression for a prolonged period, triggered even after the brain growth spurt. Given that neurotrophic factors play important roles in brain development, it can be speculated that the altered expression of these factors induced by maternal separation may interrupt normal brain development and ultimately lead to functional disruption. However, the possibility of such changes leading to various functional disruptions and the underlying mechanisms involved require further study.