Oral follicular lymphoid hyperplasia: clinicopathologic of a case series / Hiperplasia linfoide folicular oral: clinicopatológico de uma série de casos

RESUMEN La hiperplasia folicular linfoide (HFL) es una proliferación linfoide reactiva que puede simular linfomas, tanto clínica como histológicamente. El objetivo de este estudio fue investigar las características clínicas, morfológicas e inmunohistoquímicas de una serie de casos de HFL en la cavidad oral y discutir importantes aspectos diagnósticos y diagnósticos diferenciales en relación con los linfomas foliculares. Un análisis retrospectivo de los registros de una base de datos de 38 años reveló nueve casos diagnosticados como HFL de la cavidad oral. La edad de los pacientes osciló entre 8 y 44 años. La mayoría de las lesiones se localizaron en la mucosa oral y la presencia de un nódulo indoloro fue el hallazgo clínico más común. El análisis histopatológico reveló proliferación de células linfoides dispuestas en patrón folicular, presentando folículos primarios y secundarios con centro germinal y zona del manto, con evidencia de macrófagos que contenían cuerpos apoptóticos en su interior, así como evidencia de figuras de mitosis típicas. Observamos el área interfolicular, los linfocitos, los macrófagos e las islas epimioepiteliales. El análisis inmunohistoquímico reveló positividad de folículos linfoides para CD20, CD68, CD3 y linfoma de células B2 (Bcl-2). La presentación clínica de HFL y las evidencias histopatológicas de folículos linfáticos que muestran centros germinales indistintos con una zona del manto mal definida pueden ser un problema debido a la similitud con el linfoma folicular.

Intraosseous maxillary mucoepidermoid carcinoma: a rare case report / Carcinoma mucoepidermoide intraósseo maxilar: um raro relato de caso

ABSTRACT An unusual case of intraosseous mucoepidermoid carcinoma is reported in a 22-year-old female, located in the posterior maxilla region. The article summarizes the main characteristics of the disease, including clinical-pathologic characteristics, treatment and prognosis.

RESUMEN Reportamos un caso raro de carcinoma epidermoide intraóseo ubicado en región posterior de la maxila en una paciente de 22 años de edad. El artículo resume las principales características del proceso neoplásico, incluyendo las características clínico-patológicas, el tratamiento y el pronóstico.

RESUMO Relatamos um raro caso de carcinoma mucoepidermoide intraósseo localizado em região posterior da maxila em uma paciente de 22 anos de idade. O artigo resume as principais características do processo neoplásico, incluindo as características clinicopatológicas, o tratamento e o prognóstico.

Detection of sputum cofilin-1 as indicator of malignancy.

Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.

Splenic torsion, a challenging diagnosis: Case report and review of literature.

INTRODUCTION: Wandering spleen is an unusual condition characterized by hypermobility of the spleen. This is a rare clinical entity and it's more common in childhood under 1 year of age and in third decade of life. In this second peak, it's more frequent in females. Clinical manifestations can vary from asymptomatic to abdominal emergency. Treatment is often surgical. PRESENTATION OF CASE: We presented a case report of splenic torsion from our hospital and a review of cases described in literature. This is a 40 year-old woman with complaints of upper abdominal pain associated with nausea and vomiting. A marked tenderness and a palpable abdominal mass on left hypochondrium were found as well as a slight increase in inflammatory parameters. A CT was performed and demonstrated findings compatible with splenic torsion. Surgery was performed doing laparoscopic splenectomy; Review of literature was made using the keyword combination: "wandering spleen". The research resulted in 451 articles. DISCUSSION: The physical examination and CT are fundamental for diagnosis. Surgery was performed and laparoscopic splenectomy was made because infarcted spleen; about the review of literature, the majority of patients were female and the average age at the time of diagnosis was 25.2 years. 69.5% needed splenectomy and 78.6% of surgeries were laparotomic. CONCLUSION: Splenic torsion is a rare but important differential diagnosis in patients presenting with acute abdomen. Diagnosis should be made promptly before development of life-threatening complications. Surgery is often necessary and splenopexy or splenectomy can be done.

Oral pigmentations in Laugier-Hunziker syndrome: a case report and review of diagnostic criteria / Pigmentações orais na síndrome de Laugier-Hunziker: relato de caso e revisão dos critérios de diagnóstico

ABSTRACT Laugier-Hunziker syndrome (LHS) is a rare mucocutaneous disorder, of unknown etiology, characterized by multiple hyperpigmented macules, dispersed mostly on the oral mucosa, occasionally associated with longitudinal ridging of the nails. The diagnosis requires exclusion of other conditions, such as Addison's disease and Peutz-Jeghers syndrome. We report a case of a 34-year-old male patient, presenting with hyperpigmented macules on the lips, buccal mucosa and palate, as well as mild dark striations on toenails. After careful clinical and laboratorial investigations, the diagnosis of LHS was established. Given the lack of aesthetic complaints and symptoms, no treatment was necessary.

RESUMO A síndrome de Laugier-Hunziker (SLH) é uma rara desordem mucocutânea, de etiologia indeterminada, caracterizada por múltiplas máculas hiperpigmentadas, dispersas principalmente na mucosa oral, por vezes associadas a estrias longitudinais nas unhas. O diagnóstico requer exclusão de condições como doença de Addison e síndrome de Peutz-Jeghers. Descrevemos o caso de um paciente do sexo masculino, 34 anos, com presença de máculas hiperpigmentadas em lábios, mucosa jugal e palato, além de discretas estrias enegrecidas nas unhas dos pés. Após minuciosa investigação clínica e laboratorial, foi estabelecido o diagnóstico de SLH. Dada a ausência de queixas estéticas e sintomatologia, nenhum tratamento foi necessário.

Detection of sputum cofilin-1 as indicator of malignancy

Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.

Avaliação da suplementação antioxidante na dieta para galos de matrizes pesadas em idade avançada sobre parâmetros reprodutivos / Evaluation of antioxidant supplementation in diet for aging broiler breeder roosters on reproductive parameters

Objetivou-se avaliar os efeitos de antioxidantes suplementados às dietas de galos de matrizes pesadas em idade avançada sobre as características reprodutivas. Foram utilizados galos da linhagem Cobb com 47 semanas de idade. Estes foram distribuídos em quatros tratamentos, de acordo com a adição de antioxidante à dieta, sendo: A = grupo controle (sem suplementação antioxidante); B = suplementação de 9ppm de citranaxantina; C = suplementação de 6ppm de cantaxantina e D = 150ppm de vitamina E. Foram avaliadas as características seminais, tais como volume, vigor, motilidade e concentração, a composição de ácidos graxos do sêmen (saturados, insaturados, monoinsaturados, poli-insaturados, ômega 3, ômega 6 e ômega 9) e a correlação entre o peso dos testículos e o peso dos galos. Não foram observados efeitos das substâncias antioxidantes testadas sobre os parâmetros reprodutivos avaliados. Os antioxidantes avaliados não influenciam as respostas reprodutivas de machos reprodutores de matrizes pesadas em idade avançada.(AU)

This study aimed to evaluate the effect of antioxidant supplementation in diets of aging broiler breeder roosters on reproductive characteristics. Cobb roosters were divided into four groups, according to antioxidant addition, where: A = control group (without antioxidant supplementation); B = 9ppm of citranaxanthin; C = 6ppm of canthaxanthin, and D = 150ppm of vitamin E. Seminal characteristics (volume, force, motility and concentration), semen fatty acid composition (saturated, unsaturated, monounsaturated, polyunsaturated, ω3, ω6 and ω9), and the correlation between testis weight with rooster weight were evaluated. No effects of the antioxidants tested were observed. The antioxidants do not influence the reproductive responses of aging male broiler breeder.(AU)

Immunohistochemical study of macrophages subpopulations associated with squamous cell carcinoma of the tongue, with and without metastasis / Estudo imuno-histoquímico das subpopulações de macrófagos associados a tumores em carcinoma epidermoide de língua, com e sem metástase

ABSTRACT Introduction: Stromal cells interact with tumor cells and play an important role in cancer invasion and metastasis. Tumor-associated macrophages (TAMs) can exhibit M1 phenotype, important immune effector cells, or M2 phenotype, able to suppress the function of M1 macrophages and influence angiogenesis and tissue repair. The CD68 antibody recognizes M1 and M2 macrophages, whereas CD163 antibody is specific only to identify M2 macrophages. Objective: To investigate the presence of TAMs in a number of cases squamous cell carcinoma (SCC) of the tongue by associating it with the occurrence of metastasis. Material and methods: Immunohistochemistry was used to evaluate the immunopositivity for CD68 and CD163 in 27 cases of SCC of the tongue. Results: The percentage of CD68 positive macrophages was higher than CD163 positive macrophages in all specimens studied. Comparing CD163 and CD68 immunostaining in the studied groups, it was observed that cases without metastasis had a higher percentage of CD68 positive cells in relation to CD163 positive cells, which was statistically significant. Conclusion: Considering these results, there was a predominance of M1 macrophages in SCC of the tongue cases without metastasis, suggesting the influence of these cells in clinical behavior of the lesion.

RESUMO Introdução: As células do estroma interagem com as células neoplásicas e desempenham papel importante na invasão e na metástase do câncer. Os macrófagos associados ao tumor (TAMs) podem se apresentar com fenótipo M1, importantes células efetoras, ou fenótipo M2, capazes de suprimir a função dos macrófagos M1 e influenciar na angiogênese e no reparo tecidual. O anticorpo CD68 reconhece os macrófagos M1 e M2, enquanto o anticorpo CD163 é específico para a identificação apenas de macrófagos M2. Objetivo: Investigar a presença dos TAMs em uma série de casos de carcinoma epidermoide (CE) de língua, associando-a à ocorrência de metástase. Material e métodos: A técnica imuno-histoquímica foi utilizada para avaliar a imunopositividade ao CD68 e CD163 em 27 casos de CE de língua. Resultados: A porcentagem de macrófagos CD68 positivos foi maior do que a de macrófagos CD163 positivos em todos os espécimes estudados. Comparando a imunomarcação de CD68 e CD163 nos grupos estudados, verificou-se que nos casos sem metástase havia maior proporção de células CD68 positivas em relação às CD163 positivas, o que foi estatisticamente significativo. Conclusão: Diante desses resultados, observou-se a predominância de macrófagos M1 em casos de CE de língua sem metástase, sugerindo a influência dessas células no comportamento clínico da lesão.

Transanal total mesorectal excision: a pure NOTES approach for selected patients.

BACKGROUND: The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various "incisionless" procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. METHODS: Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. RESULTS: The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. CONCLUSIONS: The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles.

Retrospective analysis of the histopathologic features of 288 cases of reactional lesions in gingiva and alveolar ridge.

INTRODUCTION: The aim of this study was to perform a retrospective study of histopathologic features of a series of cases of pyogenic granuloma (PG), peripheral giant cell lesion (PGCL), and peripheral ossifying fibromas (POF) that constitutes the group called reactional lesions, located in gingiva and alveolar ridge. STUDY DESIGN: Cases of PG, PGCL, and POF were selected for this study. The morphological analysis of the lesions constituted the following: intensity of inflammatory infiltrate (IF), presence of vascular proliferation (VP), fibroblastic proliferation (FP), areas of ulceration (AU), bacterial colony (BC), presence of mineralization (PM), multinucleated giant cells (MGC), hemosiderin deposition (HD), hemorrhage area (HA). RESULTS: Of the 288 cases analyzed, 162 (56.3%) were PG, 72 (25%) were PGCL, and 54 (18.8%) were POF. The IF, VP, AU, and BC were more prominent in PG (85.8%, 98.8%, 91.4%, and 46.9%, respectively) and PM in POFs (98.1%). FP was more frequent in POF (98.1%) and PGCL (100%) and MGC in PGCL (100%), although some cases of POF (7.4%) and PG (0.6%) exhibited MGC. HD was more frequent in PGCL (40.3%) and HA in PG (53.1%). CONCLUSIONS: This study demonstrated that IF, VP, AU, BC, and HA are the common features in PG, MGC, FP, and HD are the most common in PGCL, and PM associated with FP are the most common in POF, which can help in the histopathologic differential diagnosis between these lesions. In addition, it may suggest a possible development and maturation of the PG in POF with reduction in the inflammatory component and increase in the fibrous component.

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids.

Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.

Immunoexpression of bone morphogenetic protein-2 (BMP-2), BMP receptor type IA, and BMP receptor type II in metastatic and non-metastatic lower lip squamous cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the expression of bone morphogenetic protein-2 (BMP-2), BMPR-IA, and BMPR-II in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). METHODS: Twenty LLSCC with regional nodal metastasis and 20 LLSCC without metastasis were selected for analysis of the immunoexpression of BMP-2, BMPR-IA, and BMPR-II. The percentage of positive cells was evaluated according to the following parameters: score 1 (staining in 0-50% of cells), score 2 (staining in 51-75% of cells), and score 3 (staining in >75% of cells). Immunostaining intensity was evaluated according to the following scores: score 1 (absent or weak expression) and score 2 (strong expression). RESULTS: Regarding the percentage of positive cells, most tumors with and without metastasis showed score 3 for both BMP-2 (P = 0.655) and BMPR-IA (P = 0.655). For BMPR-II, metastatic tumors exhibited higher percentage of positive cells in comparison with non-metastatic tumors (P = 0.049). With respect to immunostaining intensity, most LLSCCs with and without metastasis showed score 2 for BMP-2 (P = 1.000) and score 1 for BMPR-II (P = 1.000). For BMPR-IA, most metastatic tumors presented score 2, whereas most non-metastatic tumors showed score 1 (P < 0.001). Strong expression of BMPR-IA showed a statistically significant association with advanced clinical staging (P < 0.001) and high score of malignancy (P = 0.028). CONCLUSIONS: The results of this study suggest that disturbances in the BMP-2 signaling pathway may be involved in the development of LLSCC and that the strong expression of BMPR-IA might be indicative of the development of metastasis in these lesions.

Endovascular treatment for chronic arteriovenous fistula between renal artery and inferior vena cava: image in vascular surgery.

Arteriovenous fistula involving renal artery and inferior vena cava are rare. We report the case of a 47-year-old woman with a chronic arteriovenous fistula between right renal artery and inferior vena cava due to a penetrating trauma. Another finding was a vena cava aneurysm caused by the fistula. The patient was successfully treated with a covered stent in the renal artery. Diagnosis and postoperative control have been documented with CT scan. Endovascular techniques may be effective and minimally invasive option for treatment and renal preservation in renal-cava arteriovenous fistulae.

Treadmill test is limited in elderly patients with peripheral arterial disease.

BACKGROUND: To describe the applicability and the performance of the treadmill test in elderly patients with peripheral arterial disease (PAD) and without PAD (non-PAD). PATIENTS AND METHODS: Fifty consecutive PAD and non-PAD elderly patients performed a progressive treadmill test. The proportion of patients who were unable to perform the test and the maximal walking distance were obtained. RESULTS: The proportion of patients who were unable to perform the treadmill test was similar between PAD (16.6 %) and non-PAD patients (12.5 %), P = .57. Maximal walking time for patients who performed the treadmill test was not different between PAD (232 +/- 218 s) and non-PAD patients (308 +/- 289 s), P = .37. CONCLUSIONS: The treadmill test is limited in almost 20 % of elderly patients with PAD and non-PAD. These results highlight the need for other forms of exercise stress tests in order to assess the peripheral limitation of patients with PAD.

Neutropenia e mucosite oral: fatores de risco para candidiase em crianças com câncer / Neutropenia and oral mucositis: risck factors for candidiasis in children with cancer

A mucosite oral (MO) representa uma complicação estomatológica desafiante em pacientes com câncer, a qual pode causar significativa morbidade e comprometimento dos protocolos de tratamento, podendo ainda representar um risco significativo de infecções oportunista, particularmente em pacientes neutropênicos. Mediante inspeção clinica foi avaliada a ocorrência de MO e candidíase em 40 crianças com neoplasias. A MO foi observada em 13 crianças com neoplasias sistêmicas (n = 25) e 3 com tumores sólidos (n = 15), sem diferença estatisticamente significativa na ocorrência desta complicação entre as crianças com neoplasias sistêmicas e aquelas com tumores sólidos (p = 1,69). Observou-se que 5 crianças em tratamento para neoplasias sistêmicas desenvolveram em conjunto 10 lesões de candidíase, porém sem diferença estatisticamente significativa na ocorrência desta infecção entre as crianças com neoplasias sistêmicas e aquelas com tumores sólidos (p = 0,08). Constatou- se a ocorrência de 26 (7,3%) episódios de neutropenia, sendo 5 destes associados à ocorrência candidiase, nenhum dos quais ocorreu associado à presença concomitante de MO. A neutropenia contribui para o desenvolvimento de candidíase, a qual pode ser agravada pela falta de higiene oral, entre outros fatores.

The oral mucositis (OM) is a challenging stomatologic complication in patients with cancer, which may cause significant morbidity and impairment of treatment protocols and may represent a significant risk of opportunistic infections, particularly in neutropenic patients. Upon inspection clinic was assessed the occurrence of OM and candidiasis in 40 children with malignancies. By hematologic laboratorial exam was availed de absolute neutrophil count (ANC). The OM was observed in 13 children with systemic neoplasms (n = 25) and 3 with solid tumors (n = 15), no statistically significant difference was observed in the occurrence of this complication among children with systemic malignanciesand those with solid tumors (p = 1, 69). It was observed that 5 children in treatment for systemic cancers developed together 10 lesions of candidiasis, but no statistically significant difference was observed in the occurrence of this infection among children with systemic malignancies and those with solid tumors (p = 0.08). It was observed the occurrence of 26 (7.3%) episodes of neutropenia, 5 of them associated with the occurrence of candidiasis, none of which were associated with concomitant presence of OM. The neutropenia contributes to the development of candidiasis, which may be aggravated by defficient oral hygiene, among other factors.

Chondrolipoma of the tongue: a case report.

Chondrolipomas are benign mesenchymal tumors characterized by the proliferation of mature adipocytes associated with variable amounts of mature cartilaginous tissue. We describe here a case of chondrolipoma of the tongue in a 30-year-old man. The patient reported the presence of the lesion for approximately 10 years. Intraoral clinical examination revealed a nodular, sessile, pink mass of firm consistency, which was located along the midline of the posterior region on the dorsal surface of the tongue. An excisional biopsy was performed and histopathological examination revealed a well-delimited proliferation of mature adipocytes arranged in lobules and separated by fibrous connective tissue septa. Islands of mature cartilaginous tissue were identified in close proximity to the fibrous connective tissue septa, as well as lacunae filled with chondrocytes. No myxoid areas, lipoblasts, atypias, hyperchromasia or mitosis were detected. After 5 years of follow-up, the patient shows no signs of recurrence. Chondrolipomas are uncommon in the oral cavity, with only nine cases being reported in the international literature (Pubmed Database).

Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogen-synthase-kinase-3beta.

Mood disorders are the most common psychiatric disorders. Although the mechanisms implicated in the genesis of mood disorders are still unclear, stress is known to predispose to depression, and recently, studies have related hippocampal neurogenesis and apoptosis to depression. In the present study we first examined the balance between cell birth-death in the hippocampus and subventricular zone (SVZ) of pre-pubertal and adult rats subjected to chronic-mild-stress (CMS). CMS led to increased corticosterone secretion and induced depressive-like symptoms (assessed in the forced-swimming test); these endocrine and behavioral effects were paralleled by decreased hippocampal, but not SVZ, cell proliferation/differentiation and by increased apoptotic rate. In order to determine if lithium, a known mood stabilizer with antidepressant properties, could prevent the stress-induced events, we analyzed the same parameters in a group of rats treated with lithium during the stress exposure period (CMS+Li) and observed that the hormonal, behavioral and cell turnover effects of CMS were abrogated in these animals. Subsequently, to search for possible pathways through which CMS and lithium influence behavior, cell fate and synaptic plasticity, we analyzed the expression of glycogen-synthase-kinase-3beta (GSK-3beta), as well as some of its downstream targets (B-cell-CLL/lymphoma2-associated athanonege (BAG-1) and synapsin-I). CMS increased GSK-3beta and decreased synapsin-I and BAG-1 expression in the hippocampus. Interestingly, co-administration of lithium precluded the CMS-induced effects in GSK-3beta, synapsin-I and BAG-1 expression. Our observation that specific inhibition of this kinase with AR-A014418 blocked the effects of CMS in depressive-like behavior and in BAG-1 and synapsin-I expression confirmed the involvement of the GSK-3beta pathway in stress-induced effects. In summary, these results reveal that lithium, by regulating the activity of GSK-3beta, prevents the deleterious effects of stress on behavior and cellular functions.