Developmental complex trauma induces the dysfunction of the amygdala-mPFC circuit in the serotonergic and dopaminergic systems.

Developmental complex trauma is strongly associated with various psychiatric disorders in adulthood. Multiple lines of evidence have demonstrated that the amygdala-mPFC circuit regulates emotion and plays an important role in stress reactions. However, most studies on developmental trauma have mainly focused on neurological aspects in biological, behavioral, and structural changes with regard to a single stressor. In the present study, after applying complex stressors to the developmental phase, we would like to elucidate the functional changes in amygdala-mPFC circuit in the dopaminergic and serotonergic systems in the adult brain. Here, maternal separation and restraint stress were used to generate the trauma. The results showed that the body weights and corticosterone levels of animals exposed to developmental trauma decreased when compared to controls. In the neuroendocrine aspect, trauma leads to changes in proinflammatory cytokines, resulting in a decrease in IL-ß and an increase in TNF-α. In the neuroPET studies, the developmental trauma group displayed a reduction in serotonergic and dopaminergic PET uptake in the amygdala and mPFC. Collectively, our results indicate that developmental trauma weakens the serotonergic and dopaminergic systems in the amygdala-mPFC circuit.

Does meniscectomy have any advantage over conservative treatment in middle-aged patients with degenerative medial meniscus posterior root tear?

BACKGROUND: The best treatment for degenerative medial meniscus posterior root tear (MMPRT) remains controversial. This study aimed to compare the clinical and radiological outcomes of arthroscopic meniscectomy and conservative treatment for degenerative MMPRT. METHODS: From January 2007 to December 2014, 146 patients (Meniscectomy group, 90; Conservative group, 56) were evaluated. Clinical outcomes were assessed using the Visual Analog Scale, International Knee Documentation Committee subjective scoring scale, Tegner activity scale, and Lysholm knee scoring scale at the final follow-up. Radiologic outcomes evaluated the progression of osteoarthritis (OA) according to the Kellgren-Lawrence (K-L) classification. We compared the hip-knee-ankle angle (HKAA), medial proximal tibial angle, tibial posterior slope angle, and width of medial joint space. After an average follow-up of 6.3 years, the survivorship was analyzed using the Kaplan-Meier method. RESULTS: All clinical outcomes were significantly improved in both groups after treatment, with no significant differences between the two groups at the final follow-up. The progression of OA according to the K-L classification, HKAA and width of medial joint space was significantly advanced in the meniscectomy group (p = 0.03, 0.04, 0.03, respectively). The 10-year survival rates in the meniscectomy and conservative groups were 87 and 88%, respectively. CONCLUSIONS: This study demonstrated that both conservative treatment and meniscectomy provided symptomatic relief. However, it was confirmed that OA progression was more severe in the meniscectomy. We conclude that arthroscopic meniscectomy had no advantage over conservative treatment in terms of clinical outcomes and OA progression in middle-aged patients with MMPRT. LEVEL OF EVIDENCE: Level III; retrospective comparative study.

Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Are More Effective Than Bone Marrow Aspiration Concentrate for Cartilage Regeneration After High Tibial Osteotomy in Medial Unicompartmental Osteoarthritis of Knee.

PURPOSE: The purpose of this study was to compare the outcome of cartilage regeneration between bone marrow aspirate concentrate (BMAC) augmentation and allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSCs) transplantation in high tibial osteotomy (HTO) with microfracture (MFX) for medial unicompartmental osteoarthritis (OA) of the knee in the young and active patient. METHODS: Between January 2015 and December 2019, the patients who underwent HTO and arthroscopy with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA with kissing lesion, which was shown full-thickness cartilage defect (≥ International Cartilage Repair Society [ICRS] grade 3B) in medial femoral cartilage and medial tibial cartilage, were include in this study. Retrospectively we compared clinical outcomes, including Hospital for Special Surgery score, Knee Society Score (KSS) pain and function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between BMAC and hUCB-MSCs group at minimum of 1-year follow-up. Also, second-look arthroscopy was performed simultaneously with removal of the plate after complete bone union. Cartilage regeneration was graded by the ICRS grading system at second-look arthroscopy. Radiological measurement including hip-knee-ankle (HKA) angle, posterior tibial slope angle, and correction angle were assessed. RESULTS: Of 150 cases that underwent HTO with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA, 123 cases underwent plate removal and second-look arthroscopy after a minimum of 1 year after the HTO surgery. Seventy-four cases were kissing lesion in medial femoral cartilage and medial tibial cartilage during initial HTO surgery. Finally, the BMAC group composed of 42 cases and hUCB-MSCs group composed of 32 cases were retrospectively identified in patients who had kissing lesions and second-look arthroscopies with a minimum of 1 year of follow-up. At the final follow-up of mean 18.7 months (standard deviation = 4.6 months), clinical outcomes in both groups had improved. However, there were no significant differences between the IKDC, WOMAC, or KSS pain and function scores in the 2 groups (P > .05). At second-look arthroscopy, the ICRS grade was significantly better in the hUCB-MSC group than in the BMAC group in both medial femoral and medial tibial cartilage (P = .001 for both). The average ICRS grade of the BMAC group improved from 3.9 before surgery to 2.8 after surgery. The average ICRS grade of the hUBC-MSC group improved from 3.9 before surgery to 2.0 after surgery. Radiological findings comparing postoperative HKA angle, posterior tibial slope angle, and correction angle showed no significant differences between the groups (P > .05). Therefore it was found that the postoperative correction amount did not affect the postoperative cartilage regeneration results. CONCLUSIONS: We found that the hUCB-MSC procedure was more effective than the BMAC procedure for cartilage regeneration in medial unicompartmental knee OA even though the clinical outcomes improved regardless of which treatment was administered. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A survey of herbal medicines as tumor microenvironment-modulating agents.

The tumor microenvironment (TME) is extremely complex, involving extensive interactions among stromal cells, immune cells, and signaling molecules. Therefore, an approach targeting the TME has emerged as a promising therapeutic strategy. Herbal medicines consist of multiple active compounds, which have multi-target effects. Therefore, they have been regarded as potential anticancer agents; multiple studies have explored their effects on the TME. In this review, we report the effects of 29 single herb medicines or herbal formulas on the TME, based on the findings of 64 published studies. Specifically, we describe the effects of these herbal medicines on cancer-associated fibroblasts/tumor-associated fibroblasts, tumor-associated endothelial cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Among the reviewed herbal medicines, the most promising TME-modulating effects were exhibited by curcumin, DHA, EGCG, resveratrol, and silibinin; these medicines showed the ability to regulate two or more components of the TME. The findings of this review support the notion that the combination of herbal medicines with conventional anticancer therapies are likely to exhibit a clinical benefit, which should be further explored in clinical trials.

Evaluation of the Effects of Developmental Trauma on Neurotransmitter Systems Using Functional Molecular Imaging.

Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.

Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase.

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

Robust Magnetized Graphene Oxide Platform for In Situ Peptide Synthesis and FRET-Based Protease Detection.

Graphene oxide (GO)/peptide complexes as a promising disease biomarker analysis platform have been used to detect proteolytic activity by observing the turn-on signal of the quenched fluorescence upon the release of peptide fragments. However, the purification steps are often cumbersome during surface modification of nano-/micro-sized GO. In addition, it is still challenging to incorporate the specific peptides into GO with proper orientation using conventional immobilization methods based on pre-synthesized peptides. Here, we demonstrate a robust magnetic GO (MGO) fluorescence resonance energy transfer (FRET) platform based on in situ sequence-specific peptide synthesis of MGO. The magnetization of GO was achieved by co-precipitation of an iron precursor solution. Magnetic purification/isolation enabled efficient incorporation of amino-polyethylene glycol spacers and subsequent solid-phase peptide synthesis of MGO to ensure the oriented immobilization of the peptide, which was evaluated by mass spectrometry after photocleavage. The FRET peptide MGO responded to proteases such as trypsin, thrombin, and ß-secretase in a concentration-dependent manner. Particularly, ß-secretase, as an important Alzheimer's disease marker, was assayed down to 0.125 ng/mL. Overall, the MGO platform is applicable to the detection of other proteases by using various peptide substrates, with a potential to be used in an automated synthesis system operating in a high throughput configuration.

Gold Nanoparticle-Stabilized, Tyrosine-Rich Peptide Self-Assemblies and Their Catalytic Activities in the Reduction of 4-Nitrophenol.

Peptides are suitable candidates for templates in the fabrication of various metal nanoparticles (NPs) because of their metal-binding ability and templating effect, which impart physicochemical properties to the produced nanoparticles. Peptide-binding gold nanoparticles (AuNPs) show high catalytic activity that permits their application in oxidation or reduction reactions. Herein, we prepared morphology-controllable AuNPs stabilized by self-assembled tyrosine-rich peptides (YC7) by varying the pH and YC7 peptide/Au3+ concentration ratio in 2-( N-morpholino)ethanesulfonic acid (MES) buffer solution. The catalytic activities of the YC7 peptide-stabilized AuNPs (YC7@AuNPs) were tested for 4-nitrophenol (4-NP) reduction, and kinetic analysis was performed to calculate the apparent rate constants and activation energies. The relatively low activation energy of the YC7@AuNPs could be explained by the hypothesis that the tyrosine-moiety of YC7 enriches the electron density of Au metal.

Outcomes of simultaneous high tibial osteotomy and anterior cruciate ligament reconstruction in anterior cruciate ligament deficient knee with osteoarthritis.

BACKGROUND: We aimed to evaluate clinical and radiological results after simultaneous open-wedge high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction in patients with ACL deficiency combined with medial uni-compartmental osteoarthritis (OA) and varus deformity. METHODS: This retrospective study was performed using data collected from 2005 to 2011 on a total of 24 patients who were diagnosed with ACL injury and medial unicompartmental OA with varus deformity, and who subsequently underwent simultaneous open-wedge HTO and arthroscopic ACL reconstruction. The mean follow-up duration was 5.2 years. For clinical outcomes, we evaluated Lysholm score, Tegner activity score, range of motion, Lachmann test, and pivot-shift test, and for radiological outcomes, we evaluated the degree of varus deformity, progression of medial OA, tibial posterior slope, anterior instability, and postoperative complication. RESULTS: There were no limitations in range of motion found in any cases. Three patients showed progressive osteoarthritis on the medial compartment. The mechanical femorotibial angle was significantly corrected from varus 7.0 degrees to valgus 1.2 degrees, and the tibial posterior slope was not significantly changed. The Lysholm and Tegner activity scores were significantly improved after surgery (from 58 to 94 points on the Lysholm scale and from 4.0 to 5.3 points on the Tegner activity scale). Although the Lachman test and the pivot-shift test showed significant improvements after surgery, instability greater than Gr II was observed in three patients on the Lachman test and in four patients on the pivot-shift test. The side-to-side difference improved from 9.6 mm to 4.2 mm postoperatively as assessed using a Telos® arthrometer. There were no cases of nonunion or fixation loss. CONCLUSIONS: Simultaneous open-wedge HTO and ACL reconstruction in patients with ACL injury with medial compartmental OA showed satisfactory functional outcomes and postoperative activity level scores. However, some patients showed residual instability and progression of OA.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.

The development status of PET radiotracers for evaluating neuroinflammation.

Neuroinflammation is associated with the pathophysiologies of neurodegenerative and psychiatric disorders. Evaluating neuroinflammation using positron emission tomography (PET) plays an important role in the early diagnosis and determination of proper treatment of brain diseases. To quantify neuroinflammatory responses in vivo, many PET tracers have been developed using translocator proteins, imidazole-2 binding site, cyclooxygenase, monoamine oxidase-B, adenosine, cannabinoid, purinergic P2X7, and CSF-1 receptors as biomarkers. In this review, we introduce the latest developments in PET tracers that can image neuroinflammation, focusing on clinical trials, and further consider their current implications.

Experimental evidence for anti-metastatic actions of apigenin: a mini review.

Cancer metastasis is responsible for the majority of cancer-related deaths. Accordingly, to reduce metastasis remains a vital challenge in clinical practice, and phytochemicals have taken an attention as anti-metastatic agents. Apigenin, a plant flavone, showed anti-cancer effects against in various animal models, moreover its potentials inhibiting tumor metastasis have been reported. Herein, we analyzed the overall features at what apigenin inhibited metastasis and its action modes. We searched for articles in MEDLINE (Pubmed), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) through March 2023. Total 6 animal studies presented anti-metastatic effects of apigenin using 5 difference experimental models, while the mechanisms involved modulations of epithelial-mesenchymal transition (EMT), matrix metalloproteinases (MMPs), angiogenesis, and various metastasis-related signaling pathways. This review provides an overall potential of apigenin as a candidate reducing the risk of cancer metastasis.

Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: randomized, double blind, placebo-controlled clinical trial with parallel design.

OBJECTIVE: To examine the efficacy of Korean red ginseng for improving blood flow in healthy people. METHODS: Participants were randomized and treated with 1500 mg of Korean red ginseng extract or placebo for 8 weeks. The effect of Korean red ginseng was evaluated by digital infrared thermal images, and Doppler sonography, and blood test. RESULTS: Forty subjects completed the protocol. Imbalance in local thermal distribution was significantly decreased in the Korean red ginseng group confirmed by digital infrared thermal images. Doppler sonography showed no significant change in maximum and average rates of blood circulation in single or complex areas. Blood analyses for coagulation and lipid metabolism factors revealed no significant changes. No abnormal reactions to the Korean red ginseng were observed. CONCLUSION: Digital infrared thermal imaging showed that the temperature deviation in the whole body decreased safely in the Korean red ginseng group, which mitigated the body-temperature imbalance. This result suggests that the Korean red ginseng improves blood circulation in the human body.

A Review of Herbal Resources Inducing Anti-Liver Metastasis Effects in Gastrointestinal Tumors via Modulation of Tumor Microenvironments in Animal Models.

Liver metastases remain a major obstacle for the management of all types of tumors arising from digestive organs, and the tumor microenvironment has been regarded as an important factor in metastasis. To discover herbal candidates inhibiting the liver metastasis of tumors originating from the digestive system via the modulation of the tumor microenvironment and liver environment, we searched three representative public databases and conducted a systematic review. A total of 21 studies that employed experimental models for pancreatic (9), colon (8), and stomach cancers (4) were selected. The herbal agents included single-herb extracts (5), single compounds (12), and multiherbal decoctions (4). Curcuma longa Linn was most frequently studied for its anti-colon-liver metastatic effects, and its possible mechanisms involved the modulation of tumor microenvironment components such as vascular endothelial cells and immunity in both tumor tissues and circulating cells. The list of herbal agents and their mechanisms produced in this study is helpful for the development of anti-liver metastasis drugs in the future.

Trend Shift in the Cause of Revision Total Knee Arthroplasty over 17 Years.

Background: The number of revision total knee arthroplasty (TKA) has been increasing. Although many studies have analyzed the causes of revision TKA in Western countries, a limited number of studies have analyzed changes in causes of or trends in revision TKA in Asia. This study analyzed and determined the frequency and causes of failures after TKA in our hospital. We also analyzed the differences and trends over the past 17 years. Methods: A total of 296 revision TKAs performed in a single institution from 2003 to 2019 were analyzed. During the 17-year study period, patients who had undergone primary TKA between 2003 and 2011 were classified into a past group, while those who had undergone primary TKA from 2012 to 2019 were classified into a recent group. A revision performed within 2 years after primary TKA was defined as early revision. Further, differences in causes of revision TKA according to the interval from primary TKA to revision TKA were determined. The causes of revision TKA were analyzed through a comprehensive analysis of patients' medical records. Results: Overall, infection was the most common cause of failure (151/296 cases, 51.0%). Compared to the past group, the recent group had a relatively higher proportion of patients undergoing revision TKA for mechanical loosening (past group, 19.1% vs. recent group, 31.9%) and instability (11.2% vs. 13.5%) and a relatively lower proportion of patients undergoing revision TKA for infection (56.2% vs. 48.8%), polyethylene (PE) wear (9.0% vs. 2.9%), osteolysis (2.2% vs. 1.9%), and malalignment (2.2% vs. 1.0%). On comparison according to the interval from primary TKA to revision TKA, the rate of infection relatively decreased, whereas the rate of mechanical loosening and instability relatively increased in the late revision TKA compared to the early revision TKA. Conclusions: Infection and aseptic loosening were the most common reasons of revision TKA in both past and recent groups. Compared to the past, revision TKA due to PE wear has decreased significantly and revision TKA due to mechanical loosening has relatively increased recently. Orthopedic surgeons need to be aware of recent trends in mechanisms of failure and should try to recognize and address the probable causes in TKA.

Adjuvant effect of herbal medicine on transarterial chemoembolization in patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Objectives: Primary hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, especially in Asian countries. As a practical treatment option, transarterial chemoembolization (TACE) has been well applied; however, its limited efficacy remains challenging. This study analyzed the adjuvant effects of herbal medicine on TACE to determine whether it improves clinical outcomes in patients with HCC. Methods: A systematic review and meta-analysis was performed to compare the adjuvant effects of herbal medicine on TACE versus TACE therapy alone. We searched the literature from eight databases since January 2011. Results: Twenty-five studies involving 2,623 participants were selected. The adjuvant therapy of herbal medicine on TACE improved the overall survival at 0.5 years (OR = 1.70; 95% CI 1.21-2.38), 1 year (OR = 2.01; 95% CI 1.65-2.46), 2 years (OR = 1.83; 95% CI 1.20-2.80), and 3 years (OR = 1.90; 95% CI 1.25-2.91). The combination therapy also increased the tumor response rate (OR = 1.84; 95% CI 1.40-2.42). Conclusions: Despite the unsatisfactory quality of the included studies, the adjuvant therapy of herbal medicine on TACE may provide survival benefits to patients with HCC. Systematic reviews registration: http://www.crd.york.ac.uk/PROSPERO, identifier (376691).

Effect of developmental stress on the in vivo neuronal circuits related to excitation-inhibition balance and mood in adulthood.

Introduction: Traumatic events in early life have a deleterious effect on the development of normal brain developments, which may be a cause of various psychiatric disorders in adulthood. Most prior studies focused on molecular biological aspects, and research on functional changes in neural circuits is still limited. We aimed to elucidate the effect of early life stress on in vivo excitation-inhibition and serotonergic neurotransmission in the adulthood using non-invasive functional molecular imaging (positron emission tomography, PET). Methods: To compare the effect of stress intensity, early life stress animal models were divided into single trauma (MS) and double trauma groups (MRS). MS was derived from maternal separation, whereas MRS was derived from maternal separation and restraint stress after birth. And to evaluate the stress vulnerability on the sex, we used male and female rats. Results: The MRS group showed greater weight loss and more severe depressive/anxiety-like behaviors than the MS and control groups. Corticosterone levels in MRS showed a greater extent of decline than in the MS group; however, there was no significant difference in the change of T3 and T4 between MS and MRS. In the PET, the stress exposure groups showed lower brain uptake for GABAergic, glutamatergic, and serotonergic systems compared with the control group. The excitatory/inhibitory balance, which was derived by dividing glutamate brain uptake into GABAergic uptake, increased as stress intensity increased. Neuronal degeneration in the stress exposure groups was confirmed by immunohistochemistry. In the sex comparison, female showed the greater changes of body weight, corticosterone level, depressive/anxiety-like behavior, and neurotransmission systems than those in male. Conclusion: Taken together, we demonstrated that developmental stress induces dysfunction of neurotransmission in vivo, and that females are more vulnerable to stress than males.

Effects of Escitalopram on the Functional Neural Circuits in an Animal Model of Adolescent Depression.

PURPOSE: Although escitalopram is known to be an effective drug for adult depression, its disease-modifying efficacy on adolescents remains controversial. The present study aimed to evaluate the therapeutic effect of escitalopram on behavioral aspects as well as functional neural circuits by means of positron emission tomography. PROCEDURES: To generate the animal models of depression, restraint stress was used during the peri-adolescent period (RS group). Thereafter, escitalopram was administered after the end of stress exposure (Tx group). We performed NeuroPET studies of glutamate, glutamate, GABA, and serotonin systems. RESULTS: The Tx group showed no body weight change compared to the RS group. In the behavioral tests, the Tx group also displayed the similar time spent in open arms and immobility time to those for RS. In the PET studies, brain uptake values for the Tx group revealed no significant differences in terms of glucose, GABAA, and 5-HT1A receptor densities, but lower mGluR5 PET uptake compared to the RS group. In the immunohistochemistry, the Tx group showed the significant loss of neuronal cells in the hippocampus compared to the RS group. CONCLUSION: The administration of escitalopram had no therapeutic effect on the adolescent depression.