[Artificial intelligence technology enables ultrasonography in precision diagnosisand treatment of liver diseases].

Liver disease is one of the major problems affecting human health. Ultrasound plays an important role in diagnosis and treatment of diffuse and focal liver diseases. However, conventional ultrasound evaluation is subjective and provides limited information. Artificial intelligence (AI) technology may supplement the disadvantages of conventional ultrasound and has been widely used in the field of ultrasound in liver diseases. To date, remarkable progress has been achieved for the use of AI technology in the diagnosis, assessment of therapeutic efficacy and prognosis prediction of liver diseases. This paper reviews the research progress of ultrasound image-based AI technology in the diagnosis and treatment of diffuse and focal liver diseases.

Preliminary dosimetric analysis of DOTA-folate radiopharmaceutical radiolabelled with 47Sc produced through natV(p,x)47Sc cyclotron irradiation.

47Sc is one of the most promising theranostic radionuclides, thanks to its low energy γ-ray emission (159 keV), suitable for single photon emission computed tomography imaging and its intense ß - emission, useful for tumour treatment. Despite promising preclinical results, the translation of 47Sc-therapeutic agents to the clinic is hampered by its limited availability. Among different 47Sc-production routes currently being investigated, the natV(p,x)47Sc reaction has proved to be of particular interest, thanks to the low-cost and easy availability on the market of natV material and the diffusion of medium energy proton cyclotrons. However, the cross section of this specific nuclear reaction is quite low and small amounts of Sc-contaminants are co-produced at energies E P ≤ 45 MeV, namely 48Sc and 46Sc. The main concern with these Sc-contaminants is their contribution to the patient absorbed dose. For such a reason, the absorbed dose contributions to healthy organs and the effective dose contributions by the three radioisotopes, 48Sc, 47Sc and 46Sc, were evaluated using DOTA-folate conjugate (cm10) as an example of radiopharmaceutical product. Considering as acceptable the limits of 99% for the radionuclidic purity and 10% for the contribution of radioactive Sc-contaminants to the total effective dose after 47Sc-cm10 injection, it was obtained that proton beam energies below 35 MeV must be used to produce 47Sc through irradiation of a natV target.

[Special histopathological variants and potential diagnostic traps of classical follicular dendritic cell sarcoma].

Objective: To investigate the clinicopathological features, special morphologic variants and potential diagnostic traps of classical follicular dendritic cell sarcoma (FDCS). Methods: A total of 25 cases of classical FDCS diagnosed in the First Hospital Affiliated to Army Medical University from 2006 to 2018 were examined by hematoxylin-eosin staining, immunohistochemistry and in situ hybridization for Epstein-Barr virus-encoded mRNA (EBER). Meanwhile, the types and characteristics of the special variants of FDCS were summarized along with those reported in the literature. Results: The age of patients ranged from 23 to 77 years (mean 52 years), the male to female ratio was 1.5, and the maximum diameter of tumor was 1.5 to 20 cm (mean 7.4 cm). Twelve cases (48%) were misdiagnosed at the initial evaluation. Follow-up information was available for 17 patients, and the follow-up time was 5 to 96 months. The propotion of patients having recurrence, metastasis and mortality was 3/17, 5/17 and 2/17, respectively. Microscopically, besides the typical morphology, 10 cases of FDCS showed special histomorphologies and/or structures, including those mimicking lymphoepithelioma-like carcinoma, desmoplastic infiltrating carcinoma, classical Hodgkin's lymphoma (CHL), anaplastic large cell lymphoma (ALCL) and hemangiopericytoma. These morphologic variants were potential diagnostic pitfalls and warranted attention. Immunohistochemistry showed that more than two markers of follicular dendritic cells (such as CD21, CD23, CD35, etc.) were expressed in cases showing typical morphology and the special variants. All 25 cases were all negative for EBER by in situ hybridization. Conclusions: Classical FDCS is rare, besides the typical morphologic features, there are many special variants. In particular, these may be confused with lymphoepithelioma-like carcinoma in the nasopharynx, CHL or ALCL in the mediastinum/lymph node. Awareness of these variants is essential for accurate diagnosis.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Diagnostic value of joint detection of homocysteine and RDW CV on acute myocardial infarction.

The article "Diagnostic value of joint detection of homocysteine and RDW CV on acute myocardial infarction" by G.-X. Hu, J. Zhang, Y.-G. Tian, Y.-H. Li, L. Mou, L.-J. Qiao, published in Eur Rev Med Pharmacol Sci 2016; 20 (19): 4124-4128 has been withdrawn.

Clinical analysis of hyperkalemic renal tubular acidosis caused by calcineurin inhibitors in solid organ transplant recipients.

WHAT IS KNOWN AND OBJECTIVE: Calcineurin inhibitor (CNI)-based immunosuppressive regimen is widely used for preventing rejection in solid organ transplantation. Hyperkalemic renal tubular acidosis (RTA) caused by CNI is uncommon and potentially underappreciated. We reported four such cases to increase awareness of this risk and to provide recommendations for its management based on our experience. CASE SUMMARY: Four middle-aged males underwent solid organ transplant (two kidneys, one liver, one heart) and were treated with CNI-based immunosuppressive regimen (one cyclosporine A, three tacrolimus). On post-operative day 13-35, hyperkalemic hyperchloremic non-gap metabolic acidosis developed. All patients had relatively preserved renal function, normal urine output and plasma aldosterone level. Reduction in CNI dosage was partly effective; the patient on cyclosporine A was treated with fludrocortisone, and two others temporarily switched to sirolimus (SRL). WHAT IS NEW AND CONCLUSION: We should alert for CNI-induced hyperkalemic RTA in transplant recipients. By CNI dosage reduction or adding low dose fludrocortisone, or temporarily switching to SRL, the prognosis of CNI-induced hyperkalemic RTA is favourable.

Diagnostic value of joint detection of homocysteine and RDW CV on acute myocardial infarction. Retracted.

OBJECTIVE: We discussed the diagnostic value of joint detection of homocysteine (HCY) and red blood cell volume distribution width variable coefficient on acute myocardial infarction (AMI). PATIENTS AND METHODS: We collected 300 coronary heart disease cases, among which there were 121 cases of stenocardia, 65 cases of ischemic heart failure, and 114 cases of AMI at the Department of Cardiology of our hospital during the period from January 2012 to June 2013. At the same time, we took 100 normal physical examinees as the control group, used the full-automatic cell-analyzer and the immunization to measure HCY and red blood cell distribution width (RDW) CV respectively and analyze their value in diagnosing AMI. RESULTS: The differences among the four groups of HCY and RDW CV were statistically significant (p < 0.05). The HCY and RDW CV level in the AMI group were significantly higher than those of the other three groups (p < 0.05); the differences between the positive diagnosis rate of HCY, the RDW CV and their joint diagnosis in the AMI group were statistically significant (p < 0.05) while the differences between the positive diagnosis rate of HCY, the RDW CV and their joint diagnosis in the control group were not statistically significant (p > 0.05). The detection sensitivity and specificity of HCY alone were respectively 68.42% and 86.00% with those of the RDW CV alone being 64.91% and 84.00%. The joint detection sensitivity and specificity were 83.33% and 93.00%, statistically different (p < 0.05). The concordance rate, the positive predictive value and the negative predictive value were 87.85%, 93.14% and 83.04%, respectively. CONCLUSIONS: The HCY and RDW CV joint diagnosis of AMI had relatively high sensitivity, specificity, concordance rate, positive predictive value and negative predictive value.

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression.

OBJECTIVE: Although 5-fluorouracil (5-FU) is widely used in the treatment of various cancers, drug resistance remains a limitation for its anti-cancer activity. Mammalian target of rapamycin (mTOR) is deregulated in diverse human cancers, including gallbladder carcinoma and mTOR inhibitors show promising anti-cancer activities with proliferation inhibitory effects. This study aims to clarify the benefit of the combination of 5-FU and the mTOR inhibitor, OSI-027, on gallbladder carcinoma cell proliferation. MATERIALS AND METHODS: Two gallbladder carcinoma cell lines and two agents (5-FU and OSI-027) were used in the present study. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. The expression of MDR1 protein was determined by western blot analysis. RESULTS: The combination of OSI-027 with 5-FU showed a synergistic anti-proliferative effect on the gallbladder cancer cells, RBE and GBC-SD cells. Upon 5-FU treatment, MDR1 expression was upregulated and OSI-027 could reverse 5-FU-induced MDR1 upregulation. Moreover, MDR1 depletion sensitized gallbladder carcinoma cells to 5-FU stimulation and attenuated the synergistic effect of OSI-027 and 5-FU. Finally, we determined that OSI-027 downregulated MDR1 expression by suppressing its synthesis rather than by promoting its degradation. CONCLUSIONS: Dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer.

Does live music benefits patients with brain and spinal injury?

OBJECTIVE: The purpose of this study is to examine the feasibility and prospective success associated with implementing and evaluating a six-week live music intervention on an inpatient neurorehabilitation ward. PATIENTS AND METHODS: In total 26 patients were included in this study. Out of which, 15 were patients and 11 were staff members. Staff participants completed wellbeing measures at before and after music. Patients completed an assortment of validated measures at five consecutive time points from baseline to follow-up. Staff participants experienced a minor decrease in wellbeing over time. RESULTS: The majority of the data collected from patients illustrated positive trends, with improvements in wellbeing, pain, cognition functioning, independent functioning, and mobility. The feasibility indicates that with modifications that this project is a viable venture. CONCLUSIONS: We found that live music appears to be promising new addition to neurorehabilitation.

Clinical evaluation of the efficacy of the combination of aneurysm embolization and cerebrospinal fluid replacement in the treatment of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To explore the clinical efficacy of aneurysm embolization and cerebrospinal fluid (CSF) replacement in the treatment of aneurysmal subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: Seventy-nine patients with grade III-IV aneurysmal subarachnoid hemorrhage, who were treated in the hospital from Jan. 2012 to Jan. 2014, were included in this study. These patients were treated with different methods based on the cause of disease and the treatment chosen by their families. In the treatment group, 42 patients received aneurysm embolization and cerebrospinal fluid replacement, while 37 patients in the control group received simple aneurysm embolization. The treatment efficacy and the occurrence of complications in both groups were compared. RESULTS: The occurrence of cerebral vasospasm and hydrocephalus in the treatment group was significantly lower than the control group, and the difference was statistically significant. However, the mortality rate was decreased in both groups. CONCLUSIONS: Both methods had the advantage of minimal invasiveness and rapid post-operative recovery. But using combination of these two methods is clinically rational and could decrease the rate of disability and mortality.

Laparoscopic kidney transplant by extra peritoneal approach: the safe transition from laboratory to the clinic.

The aim of this study is to develop a novel laparoscopic surgery by extra-peritoneal approach for kidney transplant and pave the way of safe transition from laboratory to the clinic. The study was established to explore the feasibility and safety of human laparoscopic kidney transplant. The experiment was first conducted on the deceased animals, then live animals and human cavader before human kidney transplant was approved. The study patient was a 49-year-old male who received the kidney for laparoscopic kidney transplant by extra-peritoneal approach. The control patient received the contralateral kidney for open kidney transplant. The estimated blood loss was minimal during surgery. Both kidneys experienced delayed graft function but the kidneys started function on Day 6 postoperation. The analgesia consumption was significantly less in the study patient. There is no surgical complication during 6-month follow-up. This study has developed a new technique for laparoscopic kidney transplant by extra-peritoneal approach. It has retained the advantages of open kidney transplant, which allows the graft located in the extra-peritoneal space without violating peritoneum. This study has also paved the way of safe transition for a novel laparoscopic surgery from laboratory to the clinic.

Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex.

Immature neurons expressing doublecortin (DCX+) are present around cortical layer II in various mammals including guinea pigs and humans, especially enriched in the paleocortex. However, little is known whether and how functional experience affects the development of this population of neurons. We attempted to explore a modulation by experience to layer II DCX+ cells in the primary olfactory cortex in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were subjected to unilateral naris-occlusion, followed 1 and 2months later by morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were reduced in the deprived relative to the non-deprived piriform cortex in both age groups at the two surviving time points. The number of DCX+ cells was decreased in the deprived side relative to internal control at 1 and 2months in the youths and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells showed a trend of decrease in the deprived side relative to the internal control in the youths. In addition, DCX+ cells in the deprived side exhibited a lower frequency of colocalization with the neuron-specific nuclear antigen (NeuN) relative to counterparts. These results suggest that normal olfactory experience is required for the maintenance and development of DCX+ immature neurons in postnatal and adult guinea pig piriform cortex.

Gephyrin plays a key role in BDNF-dependent regulation of amygdala surface GABAARs.

Brain-derived neurotrophic factor (BDNF) is critically involved in synaptic plasticity and neurotransmission. Our lab has previously found that BDNF activation of neurotrophic tyrosine kinase, receptor, type 2 (TrkB) is required for fear memory formation and that GABAA receptor (GABAAR) subunits and the GABAA clustering protein gephyrin are dynamically regulated during fear memory consolidation. We hypothesize that TrkB-dependent internalization of GABAARs may partially underlie a transient period of amygdala hyperactivation during fear memory consolidation. We have previously reported that BDNF modulates GABAAR α1 subunit sequestration in cultured hippocampal and amygdala neurons by differential phosphorylation pathways. At present, no studies have investigated the regulation of gephyrin and GABAAR α1 subunits following BDNF activation in the amygdala. In this study, we confirm the association of GABAAR α1 and γ2 subunits with gephyrin on mouse amygdala neurons by coimmunoprecipitation and immunocytochemistry. We then demonstrate that rapid BDNF treatment, as well as suppression of gephyrin protein levels on amygdala neurons, induced sequestration of surface α1 subunits. Further, we find that rapid exposure of BDNF to primary amygdala cultures produced decreases in gephyrin levels, whereas longer exposure resulted in an eventual increase. While total α1 subunit levels remained unchanged, gephyrin was downregulated in whole cell homogenates, but enhanced in complexes with GABAARs. Our data with anisomycin suggest that BDNF may rapidly induce gephyrin protein degradation, with subsequent gephyrin synthesis occurring. Together, these findings suggest that gephyrin may be a key factor in BDNF-dependent GABAAR regulation in the amygdala. This work may inform future studies aimed at elucidating the pathways connecting BDNF, GABAA systems, gephyrin, and their role in underlying amygdala-dependent learning.

Meticulous use of techniques for reconstruction of multiple renal arteries in live donor kidney transplantation.

BACKGROUND: The aims of this study were to provide an overview of techniques for renal artery reconstruction and to introduce a novel technique using the gonadal vein as a "Carrel patch." MATERIALS AND METHODS: From January 2005 to December 2011, we performed 128 live donor kidney transplantations. All donor nephrectomies used laparoscopic surgery, yielding 23 grafts with 2 and 3 with 3 renal arteries. The reconstruction technique was based on the length and caliber of the arteries. For 3 renal arteries, we used the gonadal vein as a "Carrel patch". The gonadal vein was harvested with the ureter as a bundle during nephrectomy. The recipients were 1.5 to 71 years old (average, 43.9). RESULTS: All laparoscopic donor nephrectomies were performed successfully with preservation of the multiple arteries. The reconstructions were satisfactory; all grafts functioned immediately. There was no arterial infarction on postoperative Doppler ultrasound and renal nuclear scan. Renal artery stenosis occurred in 2 cases, in which the interventional balloon dilatation was first used; 1 case required subsequent stent insertion. CONCLUSION: In cases of multiple renal arteries, the live donor kidney can be recovered safely by laparoscopic surgery. Our technique to reconstruct multiple renal arteries uses the gonadal vein as a "Carrel patch." The gonadal vein is readily available during laparoscopic donor nephrectomy.

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

BACKGROUND: Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. MATERIALS AND METHODS: The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. RESULTS: All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 µmol/L on day 3; 224.5 µmol/L at week 1; 127 µmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. CONCLUSION: Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant.

First characterisation of natural radioactivity in building materials manufactured in Albania.

This study focuses on the radiological characterisation of building materials manufactured in Albania by using a high-resolution gamma-ray spectrometer. The average activity concentrations of (40)K, (226)Ra and (232)Th were, respectively, 644.1±64.2, 33.4 ± 6.4 and 42.2 ± 7.6 Bq kg(-1) in the clay brick samples and 179.7 ± 48.9, 55.0 ± 5.8 and 17.0 ± 3.3 Bq kg(-1) in the cement samples. The calculated activity concentration index (ACI), varied from 0.48±0.02 to 0.63±0.04 in the clay brick samples and from 0.29±0.03 to 0.37±0.02 in the cement samples. Based on the ACI, all of the clay brick and cement samples were categorised as A1 materials. The authors can exclude (at 3σ level) any restriction of their use as bulk materials.

In vivo knockdown of GAD67 in the amygdala disrupts fear extinction and the anxiolytic-like effect of diazepam in mice.

In mammals, γ-aminobutyric acid (GABA) transmission in the amygdala is particularly important for controlling levels of fear and anxiety. Most GABA synthesis in the brain is catalyzed in inhibitory neurons from L-glutamic acid by the enzyme glutamic acid decarboxylase 67 (GAD67). In the current study, we sought to examine the acquisition and extinction of conditioned fear in mice with knocked down expression of the GABA synthesizing enzyme GAD67 in the amygdala using a lentiviral-based (LV) RNA interference strategy to locally induce loss-of-function. In vitro experiments revealed that our LV-siRNA-GAD67 construct diminished the expression of GAD67 as determined with western blot and fluorescent immunocytochemical analyses. In vivo experiments, in which male C57BL/6J mice received bilateral amygdala microinjections, revealed that LV-siRNA-GAD67 injections produce significant inhibition of endogenous GAD67 when compared with control injections. In contrast, no significant changes in GAD65 expression were detected in the amygdala, validating the specificity of LV knockdown. Behavioral experiments showed that LV knockdown of GAD67 results in a deficit in the extinction, but not the acquisition or retention, of fear as measured by conditioned freezing. GAD67 knockdown did not affect baseline locomotion or basal measures of anxiety as measured in open field apparatus. However, diminished GAD67 in the amygdala blunted the anxiolytic-like effect of diazepam (1.5 mg kg(-1)) as measured in the elevated plus maze. Together, these studies suggest that of GABAergic transmission in amygdala mediates the inhibition of conditioned fear and the anxiolytic-like effect of diazepam in adult mice.

A new FSA approach for in situ γ ray spectroscopy.

An increasing demand of environmental radioactivity monitoring comes both from the scientific community and from the society. This requires accurate, reliable and fast response preferably from portable radiation detectors. Thanks to recent improvements in the technology, γ spectroscopy with sodium iodide scintillators has been proved to be an excellent tool for in-situ measurements for the identification and quantitative determination of γ ray emitting radioisotopes, reducing time and costs. Both for geological and civil purposes not only (40)K, (238)U, and (232)Th have to be measured, but there is also a growing interest to determine the abundances of anthropic elements, like (137)Cs and (131)I, which are used to monitor the effect of nuclear accidents or other human activities. The Full Spectrum Analysis (FSA) approach has been chosen to analyze the γ spectra. The Non Negative Least Square (NNLS) and the energy calibration adjustment have been implemented in this method for the first time in order to correct the intrinsic problem related with the χ(2) minimization which could lead to artifacts and non physical results in the analysis. A new calibration procedure has been developed for the FSA method by using in situ γ spectra instead of calibration pad spectra. Finally, the new method has been validated by acquiring γ spectra with a 10.16 cm × 10.16 cm sodium iodide detector in 80 different sites in the Ombrone basin, in Tuscany. The results from the FSA method have been compared with the laboratory measurements by using HPGe detectors on soil samples collected particular, the (137)Cs isotopes has been implemented in the analysis since it has been found not negligible during the in-situ measurements.

Rapid brain-derived neurotrophic factor-dependent sequestration of amygdala and hippocampal GABA(A) receptors via different tyrosine receptor kinase B-mediated phosphorylation pathways.

During the consolidation of fear memory, it has been shown that GABA(A) receptors (GABA(A)R) are rapidly downregulated in amygdala. This rapid decrease in GABA(A)R functioning may permit transient hyperexcitablity, contributing to cellular mechanisms of memory consolidation. Memory consolidation also requires brain-derived neurotrophic factor (BDNF) activation of tyrosine receptor kinase B (TrkB) receptors in the amygdala and hippocampus. We hypothesized that rapid internalization of GABA(A)Rα1 is mediated via TrkB activation of PKA and PKC-dependent processes. Primary neuronal cell cultures, from postnatal day 14-21 mouse amygdala and hippocampus, were analyzed with immunofluorescence using cell-surface, whole-cell permeabilization, and antibody internalization techniques, as well as with (3)H-muscimol binding assays. In both hippocampal and amygdala cultures, we found a >60% reduction in surface GABA(A)Rα1 within 5 min of BDNF treatment. Notably, the rapid decrease in surface GABA(A)Rα1 was confirmed biochemically using surface biotinylation assays followed by western blotting. This rapid effect was accompanied by TrkB phosphorylation and increased internal GABA(A)Rα1 immunofluorescence, and was blocked by k252a, a broad-spectrum tyrosine kinase antagonist. To further demonstrate TrkB specificity, we used previously characterized TrkB(F616A) mice, in which the highly selective TrkB-mutant specific antagonist, 1NMPP1, prevented the BDNF-dependent GABA(A)Rα1 internalization. In hippocampus, we found both PKA and PKC inhibition, using Rp-8-Br-cAMP and Calphostin C, respectively, blocked GABA(A)Rα1 internalization, whereas inhibition of MAPK (U0126) and PI3K (LY294002) did not prevent rapid internalization. By contrast in amygdala cultures, Rp-8-Br-cAMP had no effect. Together, these data suggest that rapid GABA(A)R internalization during memory consolidation is BDNF-TrkB dependent. Further, it appears that hippocampal GABA(A)R internalization is PKA and PKC dependent, while it may be primarily PKC dependent in amygdala, implying differential roles for TrkB-dependent kinase activation in BDNF-dependent memory formation.