Auditory training remodels hippocampus-related memory in adult rats.

Consequences of perceptual training, such as improvements in discriminative ability, are highly stimulus and task specific. Therefore, most studies on auditory training-induced plasticity in adult brain have focused on the sensory aspects, particularly on functional and structural effects in the auditory cortex. Auditory training often involves, other than auditory demands, significant cognitive components. Yet, how auditory training affects cognition-related brain regions, such as the hippocampus, remains unclear. Here, we found in female rats that auditory cue-based go/no-go training significantly improved the memory-guided behaviors associated with hippocampus. The long-term potentiations of the trained rats recorded in vivo in the hippocampus were also enhanced compared with the naïve rats. In parallel, the phosphorylation level of calcium/calmodulin-dependent protein kinase II and the expression of parvalbumin-positive interneurons in the hippocampus were both upregulated. These findings demonstrate that auditory training substantially remodels the processing and function of brain regions beyond the auditory system, which are associated with task demands.

Pairing with Enriched Sound Exposure Restores Auditory Processing Degraded by an Antidepressant.

Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.

Environmental noise degrades hippocampus-related learning and memory.

The neural mechanisms underlying the impacts of noise on nonauditory function, particularly learning and memory, remain largely unknown. Here, we demonstrate that rats exposed postnatally (between postnatal days 9 and 56) to structured noise delivered at a sound pressure level of ∼65 dB displayed significantly degraded hippocampus-related learning and memory abilities. Noise exposure also suppressed the induction of hippocampal long-term potentiation (LTP). In parallel, the total or phosphorylated levels of certain LTP-related key signaling molecules in the synapses of the hippocampus were down-regulated. However, no significant changes in stress-related processes were found for the noise-exposed rats. These results in a rodent model indicate that even moderate-level noise with little effect on stress status can substantially impair hippocampus-related learning and memory by altering the plasticity of synaptic transmission. They support the importance of more thoroughly defining the unappreciated hazards of moderately loud noise in modern human environments.

Particulate organic nitrates at Mount Tai in winter and spring: Variation characteristics and effects of mountain-valley breezes and elevated emission sources.

Particulate organic nitrates, among the major components of secondary organic aerosols and fine particles, play important roles in regional nitrogen cycle, ozone budget, and cloud condensation nuclei formation. However, the pollution characteristics of particulate organic nitrates at mountain areas and the effects of anthropogenic pollutant transport remain poorly understood. In this study, field sampling and measurements were conducted at a high-elevation mountain site over North China Plain in winter and spring. Total five kinds of particulate organic nitrates in fine particles were determined by ultra-high performance liquid chromatography-electrospray mass spectrometry. The average total concentrations of particulate organic nitrates were 330 ± 121 ng m-3 and 247 ± 63 ng m-3 in winter and spring. The monoterpene-derived organic nitrates were the dominant components in both seasons with their contribution higher than 70%, accounting for 1.2 ± 0.8% and 2.0 ± 1.0% in organic aerosols in winter and spring, respectively. The significantly higher levels of particulate organic nitrates in winter than spring was ascribed to the strong effects of mountain-valley breezes and coal combustion plumes. The increasing concentrations of NOx and particulate matters brought by the valley breeze at daytime facilitated the formation of MHN215, OAKN359, and OAHN361, while the rising SO2 abundance and the sulfate aerosols transported by elevated emission sources affected the formation of MDCN247 at nighttime.

Validation of a Chinese version of the dementia knowledge assessment scale in healthcare providers in China.

AIMS: To translate 25-item Dementia Knowledge Assessment Scale into Chinese and evaluate its psychometric properties amongst Chinese healthcare providers. BACKGROUND: The prevalence of dementia is increasing in China, but development of relevant training for healthcare providers is still in its infancy stage. A comprehensive, valid and reliable Chinese knowledge-of-dementia measure is needed to identify training needs and evaluate the effect of educational interventions. DESIGN: A cross-sectional survey. METHODS: The Dementia Knowledge Assessment Scale was translated into Chinese following the modified Brislin's translation model. Content and face validity were established by an expert panel in dementia care and healthcare providers. A convenience sample of 290 healthcare providers in care homes and hospitals was recruited. Construct validity was evaluated through confirmatory factor analysis, concurrent validity and known groups' comparisons method. Reliability was evaluated through internal consistency reliability and 2-week test-retest reliability. This study used the STROBE checklist for reporting. RESULTS: The content validity index was 0.98. The confirmatory factor analysis model revealed that the four-factor model was partly supported in the present study. The moderate correlation between Chinese version of Dementia Knowledge Assessment Scale and Alzheimer's Disease Knowledge Scale indicated acceptable concurrent validity. The mean score of the scale and subscale scores showed significant differences between health professionals and care assistants, except for the subscale of "Care Considerations." The reliability was demonstrated with Cronbach's alpha of .77 and intra-class correlation coefficients of each subscale between .74 and .92 among 56 respondents. CONCLUSIONS: The Chinese version of Dementia Knowledge Assessment Scale demonstrated acceptable concurrent validity but marginal factorial validity and satisfactory reliability amongst Chinese healthcare providers. Therefore, applying the four-factor structure of Chinese version scale should be considered. RELEVANCE TO CLINICAL PRACTICE: Chinese version of Dementia Knowledge Assessment Scale can be used to understand the training needs of healthcare providers in dementia.

Translation and validation of Chinese version of sense of competence in dementia care staff scale in healthcare providers: a cross-sectional study.

BACKGROUND: Healthcare providers' dementia-care competence is crucial for quality dementia care. A reliable and valid instrument is needed to assess the gaps in their dementia-care competence, and thereby identifying their educational needs. Therefore, this study aims to translate the 17-item Sense of Competence in Dementia Care Staff (SCIDS) scale into Chinese (SCIDS-C) and to validate the SCIDS-C among Chinese healthcare providers. METHODS: The translation procedure followed the modified Brislin's translation model. A cross-sectional survey was conducted using the translated version. The validity, including content validity, confirmatory factor analysis, concurrent validity and known-groups validity, was tested. Reliability in terms of internal consistency and test-retest reliability with a 2-week interval was evaluated. RESULTS: A total of 290 healthcare providers in 12 nursing homes and a hospital completed the survey. The scale-level content validity index was .99. The confirmatory factor analysis model marginally supported the original 4-factor structure. Positive but weak correlations were noted between the total score of the SCIDS-C and that of the Dementia Knowledge Assessment Scale (r = .17, p = .005) and Approaches to Dementia Questionnaire (r = .22, p < .001), suggesting acceptable concurrent validity. Differences between health professionals and care assistants were significant in two subscales scores. The internal consistency of the scale was high, with Cronbach's α of .87. Test-retest reliability was demonstrated with intra-class correlation coefficient of 0.88. CONCLUSIONS: The SCIDS-C demonstrated acceptable reliability and validity although the known-groups validity between health professionals and care assistants was not fully established. It can be used to measure the level of sense of competence and as an outcome measure in educational intervention aiming at improving dementia care among Chinese healthcare providers.

Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training.

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

Novel Simultaneous Removal Technology of NO and SO2 Using a Semi-Dry Microwave Activation Persulfate System.

As it has a simple system and a small floor area, flue gas simultaneous desulfurization and denitrification technology has a good development prospect, and related research has become a hot topic in the field of flue gas purification. In this work, a novel simultaneous removal technology of NO and SO2 from flue gas using a semi-dry microwave activation persulfate system was developed for the first time. A series of experiments and characterization analyses had been implemented to research the feasibility of this new flue gas purification technology. The oxidation products, free radicals, and mechanism of NO and SO2 simultaneous removal were revealed. The effect of the main technological parameters on NO and SO2 simultaneous removal was also studied. Relevant results demonstrated that an increase in the microwave radiation power, persulfate concentration, and O2 concentration enhanced NO and SO2 simultaneous removal. The increase of NO and SO2 concentrations weakened NO and SO2 simultaneous removal. The reagent dosage, pH value of the solution, and reaction temperature showed a dual influence on NO and SO2 simultaneous removal. Free-radical capture experiments revealed that both SO4-• and •OH that were produced by microwave activation of persulfate were the major active species and played very key roles in NO and SO2 simultaneous removal. The main products (sulfate and nitrate) and byproducts (NO2) in the tail gas were found. The process application and product post-treatment routes were also proposed. The result may provide the necessary inspiration and guidance for the development and application of microwave-activated advanced oxidation technology in the flue gas treatment area.

Auditory Training Reverses Lead (Pb)-Toxicity-Induced Changes in Sound-Azimuth Selectivity of Cortical Neurons.

Lead (Pb) causes significant adverse effects on the developing brain, resulting in cognitive and learning disabilities in children. The process by which lead produces these negative changes is largely unknown. The fact that children with these syndromes also show deficits in central auditory processing, however, indicates a speculative but disturbing relationship between lead-exposure, impaired auditory processing, and behavioral dysfunction. Here we studied in rats the changes in cortical spatial tuning impacted by early lead-exposure and their potential restoration to normal by auditory training. We found animals that were exposed to lead early in life displayed significant behavioral impairments compared with naïve controls while conducting the sound-azimuth discrimination task. Lead-exposure also degraded the sound-azimuth selectivity of neurons in the primary auditory cortex. Subsequent sound-azimuth discrimination training, however, restored to nearly normal the lead-degraded cortical azimuth selectivity. This reversal of cortical spatial fidelity was paralleled by changes in cortical expression of certain excitatory and inhibitory neurotransmitter receptor subunits. These results in a rodent model demonstrate the persisting neurotoxic effects of early lead-exposure on behavioral and cortical neuronal processing of spatial information of sound. They also indicate that attention-demanding auditory training may remediate lead-induced cortical neurological deficits even after these deficits have occurred.

Positive impacts of early auditory training on cortical processing at an older age.

Progressive negative behavioral changes in normal aging are paralleled by a complex series of physical and functional declines expressed in the cerebral cortex. In studies conducted in the auditory domain, these degrading physical and functional cortical changes have been shown to be broadly reversed by intensive progressive training that improves the spectral and temporal resolution of acoustic inputs and suppresses behavioral distractors. Here we found older rats that were intensively trained on an attentionally demanding modulation-rate recognition task in young adulthood substantially retained training-driven improvements in temporal rate discrimination abilities over a subsequent 18-mo epoch-that is, forward into their older age. In parallel, this young-adult auditory training enduringly enhanced temporal and spectral information processing in their primary auditory cortices (A1). Substantially greater numbers of parvalbumin- and somatostatin-labeled inhibitory neurons (closer to the numbers recorded in young vigorous adults) were recorded in the A1 and hippocampus in old trained versus untrained age-matched rats. These results show that a simple form of training in young adulthood in this rat model enduringly delays the otherwise expected deterioration of the physical status and functional operations of the auditory nervous system, with evident training impacts generalized to the hippocampus.

[Effect of vitamin A as an adjuvant therapy for pneumonia in children: a Meta analysis].

OBJECTIVE: To investigate the effect and safety of vitamin A supplementation in children with pneumonia through a systematic review. METHODS: Cochrane Library, EMbase, PubMed, China Biology Medicine disc, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) on vitamin A as an adjuvant therapy for pneumonia in children. Two reviewers independently screened the studies and evaluated their quality according to the inclusion and exclusion criteria. RevMan5.3 was used for the Meta analysis. RESULTS: A total of 15 RCTs with 3 021 patients were included. The Meta analysis showed that vitamin A supplementation did not reduce the mortality of children with pneumonia (P>0.05), but it increased the overall clinical response rate (P<0.05) and shortened the duration of pyrexia and cough, clearance time of signs and abnormal chest X-ray results, and length of hospital stay (P<0.05). As an adjuvant therapy, vitamin A did not increase the incidence rates of adverse reactions such as nausea, vomiting, diarrhea, allergy, and bregma bulging. CONCLUSIONS: Current evidence shows that in the treatment of pneumonia in children, vitamin A supplementation helps to relieve clinical symptoms and signs and shorten the length of hospital stay.The adjuvant therapy does not increase the incidence rates of adverse reactions.

Understanding the Selective Detection of Fe3+ Based on Graphene Quantum Dots as Fluorescent Probes: The Ksp of a Metal Hydroxide-Assisted Mechanism.

Graphene quantum dots (GQDs) have been widely used as fluorescence probes to detect metal ions with satisfactory selectivity. However, the diverse chemical structures of GQDs lead to selectivity for multiple metal ions, and this can lead to trouble in the interpretation of selectivity due to the lack of an in depth and systematic analysis. Herein, bare GQDs were synthesized by oxidizing carbon black with nitric acid and used as fluorescent probes to detect metal ions. We found that the specific ability of GQDs to recognize ferric ions relates to the acidity of the medium. Specifically, we demonstrated that the coordination between GQDs and Fe3+ is regulated by the pH of the aqueous GQDs solution. Dissociative Fe3+ can coordinate with the hydroxyl groups on the surface of the GQDs to form aggregates (such as iron hydroxide), which induces fluorescence quenching. A satisfactory selectivity for Fe3+ ions was achieved under relatively acidic conditions; this is because of the extremely small Ksp of ferric hydroxide compared to those of other common metal hydroxides. To directly survey the key parameter for Fe3+ ion specificity, we performed the detection experiment in an environment free of interference from the buffer solution, noninherent groups, and other complex factors. This study will help researchers understand the selectivity mechanisms of GQDs as fluorescence probes for metal ions, which could guide the design of other GQD-based sensor platforms.

The prognostic role of MAC30 in advanced gastric cancer patients receiving platinum-based chemotherapy.

AIM: We aimed to investigate a practical profile of MAC30 on chemotherapeutic response in gastric cancer (GC). PATIENTS & METHODS: We elected 87 GC patients receiving platinum-based chemotherapy in this study. MAC30 levels in tumor and adjuvant nontumor tissues were confirmed via reverse transcription-PCR to identify the clinical profile in GC and the correlation with therapeutic response. RESULTS: We found elevated MAC30 in GC compared with the matched adjacent nontumor tissues. GC with enhanced MAC30 exhibited poorer survival by Kaplan-Meier analysis and poor response to adjuvant platinum-based chemotherapy. A multivariate analysis showed that MAC30 was an independent prognostic factor of overall survival in GC receiving platinum-based chemotherapy. CONCLUSION: MAC30 could play as a potential biomarker for prognosis of GC with platinum-based chemotherapy.

Genetically encoded bioorthogonal tryptophan decaging in living cells.

Tryptophan (Trp) plays a critical role in the regulation of protein structure, interactions and functions through its π system and indole N-H group. A generalizable method for blocking and rescuing Trp interactions would enable the gain-of-function manipulation of various Trp-containing proteins in vivo, but generating such a platform remains challenging. Here we develop a genetically encoded N1-vinyl-caged Trp capable of rapid and bioorthogonal decaging through an optimized inverse electron-demand Diels-Alder reaction, allowing site-specific activation of Trp on a protein of interest in living cells. This chemical activation of a genetically encoded caged-tryptophan (Trp-CAGE) strategy enables precise activation of the Trp of interest underlying diverse important molecular interactions. We demonstrate the utility of Trp-CAGE across various protein families, such as catalase-peroxidases and kinases, as translation initiators and posttranslational modification readers, allowing the modulation of epigenetic signalling in a temporally controlled manner. Coupled with computer-aided prediction, our strategy paves the way for bioorthogonal Trp activation on more than 28,000 candidate proteins within their native cellular settings.

Effects of puerarin on cholinergic enzymes in the brain of ovariectomized guinea pigs.

Estrogen has beneficial effects on neurodegenerative disorders and cognitive function of postmenopausal women. Puerarin, isolated from Pueraria lobota, has been classified as a phytoestrogen, which can be highly effective against cerebrovascular diseases. In this study, the effects of puerarin on neural cholinergic system in the brain of ovariectomized guinea pigs were studied. The puerarin at the doses used (15 mg/kg body weight (bw)/day and 30 mg/kg bw/day) for 10 days had the estrogenic activity indicated by the attenuation of the reduction of uterine weight induced by ovariectomy. In brain, puerarin treatment increased choline acetyltransferase (ChAT) activity and expression in hippocampus, and increased ChAT immnuopositive signals in septal diagonal region. Puerarin treatment could suppress the increase of acetylcholinesterase expression and activity to the levels of the intact group, although they were not significantly different from those of the ovariectomized animals. Moreover, puerarin decreased the ß-amyloid immunopositive staining in hippocampus. In brief, the present study suggests that puerarin prevents the dysfunction of the neuronal cholinergic system and ameliorates the increase of ß-amyloid caused by estrogen deficiency.

[Potential involvement of abnormal increased SUMO-1 in modulation of the formation of Alzheimer's disease senile plaques and neuritic dystrophy in APP/PS1 transgenic mice].

Small ubiquitin-related modifiers (SUMOs) belong to an important class of ubiquitin like proteins. SUMOylation is a post-translational modification process that regulates the functional properties of many proteins, among which are several proteins implicated in neurodegenerative diseases. This study was aimed to investigate the changes of SUMO-1 expression and modification, and the relationship between SUMO-1 and Alzheimer's disease (AD) pathology in APP/PS1 transgenic AD mice. Using Western blot, co-immunoprecipitation and immunofluorescent staining methods, the SUMO-1 expression and modification and its relation to tau, amyloid precursor protein (APP) and ß-amyloid protein (Aß) in the 12-month-old APP/PS1 transgenic AD mice were analyzed. The results showed that: (1) Compared with the normal wild-type mice, the expression and modification of SUMO-1 increased in brain of AD mice, which was accompanied by an increase of ubiquitination; (2) In RIPA soluble protein fraction of cerebral cortex, co-immunoprecipitation analysis showed tau SUMOylated by SUMO-1 increased in AD mice, however, AT8 antibody labeled phosphorylated tau was less SUMOylated whereas PS422 antibody labeled phosphorylated tau was similar to control mice; (3) Double immunofluorescent staining showed that SUMO-1 could distributed in amyloid plaques, appearing that some of SUMO-1 diffused in centre of some plaques and some of SUMO-1 co-localized with AT8 labeled phosphorylated tau forming punctate aggregates around amyloid plaques which was concerned as dystrophic neurites, however, less Aß, APP and PS422 labeled phosphorylated tau were found co-localized with SUMO-1. These results suggest that SUMO-1 expression and modification increase abnormally in transgenic AD mice, which may participate in modulation of the formation of senile plaques and dystrophic neurites.

[Hand and wrist bone maturation in children with central precocious puberty and idiopathic short stature].

OBJECTIVE: To investigate the maturation of individual bones on the hand and wrist in children with central precocious puberty (CPP) and idiopathic short stature (ISS). METHODS: Hand and wrist films of 25 children with CPP, 29 children with ISS and 21 normal controls were evaluated by conventional Greulich-Pyle (GP) atlas method and individual bone assessment method, in which all twenty bones of the hand and wrist were evaluated based on GP atlas, including 2 radius and ulna, 7 carpal bones, 11 metacarpal and phalangeal bones, the average bone age (BA) was calculated. The differences in groups were analyzed by independent samples t test. The differences between the two methods were analyzed by paired sample t test. The differences between BA and chronological age (CA) were analyzed by ROC with SPSS 17.0. RESULTS: Compared with the normal control group, the advance of BA in the CPP group was 0.70-2.26 y (1.48 ±0.78) by the GP atlas method, while that was 0.28-2.00 y(1.14 ±0.86) by the individual bone evaluation method. In all twenty bones, the advance of metacarpal and phalangeal BA was the greatest [0.34-2.06 y(1.2±0.86)]. In the ISS group,the delay of BA was 0.47-2.91 y(-1.69±1.22) by the GP atlas method, while that was 0.48-2.50 y (-1.49±1.01) by individual bone evaluation method.The delay of carpal BA was the greatest [0.59-2.73 y(-1.66±1.07)] in all twenty bones. In the ISS group and the normal control group, there were no statistic differences between the two methods. In the CPP group, statistic difference was found between two methods. There were no statistic differences for the areas under ROC curves between two methods. CONCLUSION: The advance of metacarpal and phalangeal BA is the greatest in CPP group and the delay of carpal BA is the greatest in ISS group.Both methods provide diagnostic information for bone age in CPP and ISS children.

Reduced atmospheric sulfate enhances fine particulate nitrate formation in eastern China.

Nitrate (NO3-) is a major component of atmospheric fine particles. Recent studies in eastern China have shown the increasing trend of NO3- in contrast to the ongoing control of nitrogen oxide (NOx). Here, we elucidate the effects of reduced sulfur dioxide (SO2) on the enhancement of NO3- formation based on field measurements at the summit of Mt. Tai (1534 m a.s.l.) and present detailed modelling analyses. From 2007 to 2018, the measured springtime concentrations of various primary pollutants and fine sulfate (SO42-) decreased sharply (-16.4 % to -89.7 %), whereas fine NO3- concentration increased by 22.8 %. The elevated NO3- levels cannot be explained by the changes in meteorological conditions or other related parameters but were primarily attributed to the considerable reduction in SO42- concentrations (-73.4 %). Results from a multi-phase chemical box model indicated that the reduced SO42- levels decreased the aerosol acidity and prompted the partitioning of HNO3 into the aerosol phase. WRF-Chem model analyses suggest that such a negative effect is a regional phenomenon throughout the planetary boundary layer over eastern China in spring. This study provides new insights into the worsening situation of NO3- aerosol pollution and has important implications for controlling haze pollution in China.

TRPC1 is essential for in vivo angiogenesis in zebrafish.

RATIONALE: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development. OBJECTIVE: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development. METHODS AND RESULTS: Knockdown of zebrafish trpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide-resistant form of zebrafish trpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell-autonomous. In vivo time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV tip cells. Furthermore, Trpc1 acted synergistically with vascular endothelial growth factor A (Vegf-a) in controlling ISV growth, and appeared to be downstream to Vegf-a in controlling angiogenesis, as evidence by the findings that Trpc1 was required for Vegf-a-induced ectopic angiogenesis of subintestinal veins and phosphorylation of extracellular signal-regulated kinase. CONCLUSIONS: These results provide the first in vivo evidence that TRPC1 is essential for angiogenesis, reminiscent of the role of TRPCs in axon guidance. It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis.

Developmental Exposure to Bisphenol a Degrades Auditory Cortical Processing in Rats.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.