A new karyotype of oligoryzomys (sigmodontinae, rodentia) from central Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Biomolecular information, brain activity and cognitive functions

Molecular neurobiology has provided an explanation of mechanisms supporting mental functions as learning, memory, emotion and consciousness. However, an explanatory gap remains between two levels of description: molecular mechanisms determining cellular and tissue functions, and cognitive functions. In this paper we review molecular and cellular mechanisms that determine brain activity, and then hypothetize about their relation with cognition and consciousness. The brain is conceived of as a dynamic system that exchanges information with the whole body and the environment. Three explanatory hypotheses are presented, stating that: a) brain tissue function is coordinated by macromolecules controlling ion movements, b) structured (amplitude, frequency and phase-modulated) local field potentials generated by organized ionic movement embody cognitive information patterns, and c) conscious episodes are constructed by a large-scale mechanism that uses oscillatory synchrony to integrate local field patterns. © by São Paulo State University.

Genetic and modifying factors that determine the risk of brain tumors

Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immunosuppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immunosuppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients. © 2011 Bentham Science Publishers Ltd.

Chromosomal characteristics and karyotype evolution of oxyopidae spiders (araneae, entelegynae)

We made a cytogenetic analysis of four species of Oxyopidae and compared it with the karyotype data of all species of this family. In Hamataliwa sp, the mitotic cells showed 2n♂ = 26+X 1X 2 and telocentric chromosomes. The 2n♂ = 28, which has been described for only one oxyopid spider, is the highest diploid number reported for this family. Peucetia species exhibited distinct karyotype characteristics, i.e., 2n♂ = 20+X 1X 2 in P. flava and 2n♂ = 20+X in P. rubrolineata, revealing interspecific chromosome variability within this genus. However, both Peucetia species exhibited telocentric chromosomes. The most unexpected karyotype was encountered in Oxyopes salticus, which presented 2n♂ = 10+X in most individuals and a predominance of biarmed chromosomes. Additionally, one male of the sample of O. salticus was heterozygous for a centric fusion that originated the first chromosomal pair and exhibited one supernumerary chromosome in some cells. Testicular nuclei of Hamataliwa sp and O. salticus revealed NORs on autosomal pairs, after silver impregnation. The majority of Oxyopidae spiders have their karyotype differentiated by both reduction in diploid number chromosome number and change of the sex chromosome system to X type; however, certain species retain the ancestral chromosome constitution 2n = 26+X1X2. The most remarkable karyotype differentiation occurred in O. salticus studied here, which showed the lowest diploid number ever observed in Oxyopidae and the second lowest registered for Entelegynae spiders. © FUNPEC-RP www.funpecrp.com.br.

Side-effects of thiamethoxam on the brain andmidgut of the africanized honeybee Apis mellifera (Hymenopptera: Apidae)

The development of agricultural activities coincides with the increased use of pesticides to control pests, which can also be harmful to nontarget insects such as bees. Thus, the goal of this work was assess the toxic effects of thiamethoxam on newly emerged worker bees of Apis mellifera (africanized honeybee-AHB). Initially, we determined that the lethal concentration 50 (LC50) of thiamethoxam was 4.28 ng a.i./μL of diet. To determine the lethal time 50 (LT50), a survival assay was conducted using diets containing sublethal doses of thiamethoxam equal to 1/10 and 1/100 of the LC50. The group of bees exposed to 1/10 of the LC50 had a 41.2% reduction of lifespan. When AHB samples were analyzed by morphological technique we found the presence of condensed cells in the mushroom bodies and optical lobes in exposed honeybees. Through Xylidine Ponceau technique, we found cells which stained more intensely in groups exposed to thiamethoxam. The digestive and regenerative cells of the midgut from exposed bees also showed morphological and histochemical alterations, like cytoplasm vacuolization, increased apocrine secretion and increased cell elimination. Thus, intoxication with a sublethal doses of thiamethoxam can cause impairment in the brain and midgut of AHB and contribute to the honeybee lifespan reduction. © 2013 Wiley Periodicals, Inc.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration

Background: Activation of GABAB receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABAB receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used.Results: In fluid replete rats, baclofen (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 μl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABAB antagonist, 5 nmol/0.2 μl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate.Conclusions: Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure. © 2013 Kimura et al.; licensee BioMed Central Ltd.

Effect of the bone marrow cell transplantation on elevated plus-maze performance in hippocampal-injured mice

Several reports have shown that the hippocampus plays an important role in different aspects of the emotional control. There is evidence that lesions in this structure cause behavioral disinhibition, with reduction of reactions expressing fear and anxiety. Thus, to portray the aptitude of cell therapy to abrogate injuries of hippocampal tissue, we examined the behavioral effects of bone marrow mononuclear cells (BMMCs) transplantation on C57BL/6 mice that had the hippocampus damaged by electrolytic lesion. For this purpose, mice received, seven days after bilateral electrolytic lesion in the dorsal hippocampus, culture medium or BMMCs expressing the enhanced green fluorescent protein (EGFP) transgene. One week after transplantation, animals were tested in the elevated plus-maze (EPM). On the whole, three assessment sessions in the EPM were carried out, with seven days separating each trial. Thirty-five days after the induction of injury, mice were sacrificed and their brains removed for immunohistochemistry. The behavioral evaluation showed that the hippocampal lesion caused disinhibition, an effect which was slightly lessened, from the second EPM test, in transplanted subjects. On the other hand, immunohistochemical data revealed an insignificant presence of EGFP+ cells inside the brains of injured mice. In view of such scenario, we hypothesized that the subtle rehabilitation of the altered behavior might be a result from a paracrine effect from the transplanted cells. This might have been caused by the release of bioactive factors capable of boosting endogenous recuperative mechanisms for a partial regaining of the hippocampal functions. © 2013 Elsevier B.V.

Brain morphophysiology of Africanized bee Apis mellifera exposed to sublethal doses of imidacloprid

Several synthetic substances are used in agricultural areas to combat insect pests; however, the indiscriminate use of these products may affect nontarget insects, such as bees. In Brazil, one of the most widely used insecticides is imidacloprid, which targets the nervous system of insects. Therefore, the aim of this study was to evaluate the effects of chronic exposure to sublethal doses of imidacloprid on the brain of the Africanized Apis mellifera. The organs of both control bees and bees exposed to insecticide were subjected to morphological, histochemical and immunocytochemical analysis after exposure to imidacloprid, respectively, for 1, 3, 5, 7, and 10 days. In mushroom bodies of bees exposed to imidacloprid concentrations of LD50/10 and in optic lobes of bees exposed to imidacloprid concentrations of LD 50/10, LD50/100, and LD50/50, we observed the presence of condensed cells. The Feulgen reaction revealed the presence of some cells with pyknotic nuclei, whereas Xylidine Ponceau stain revealed strongly stained cells. These characteristics can indicate the occurrence of cell death. Furthermore, cells in mushroom bodies of bees exposed to imidacloprid concentrations of LD50/10 appeared to be swollen. Cell death was confirmed by immunocytochemical technique. Therefore, it was concluded that sublethal doses of imidacloprid have cytotoxic effects on exposed bee brains and that optic lobes are more sensitive to the insecticide than other regions of the brain. © 2013 Springer Science+Business Media New York.

Epigenetic alterations in human brain tumors in a Brazilian population

Aberrant methylation of CpG islands located in promoter regions represents one of the major mechanisms for silencing cancer-related genes in tumor cells. We determined the frequency of aberrant CpG island methylation for several tumor-associated genes: DAPK, MGMT, p14^ARF, p16^INK4a, TP73, RB1 and TIMP-3 in 55 brain tumors, consisting of 26 neuroepithelial tumors, 6 peripheral nerve tumors, 13 meningeal tumors and 10 metastatic brain tumors. Aberrant methylation of at least one of the seven genes studied was detected in 83.6% of the cases. The frequencies of aberrant methylation were: 40% for p14^ARF, 38.2% for MGMT, 30.9% for, p16^INK4a, 14.6% for TP73 and for TIMP-3, 12.7% for DAPK and 1.8% for RB1. These data suggest that the hypermethylation observed in the genes p14^ARF, MGMT and p16^INK4a is a very important event in the formation or progression of brain tumors, since the inactivation of these genes directly interferes with the cell cycle or DNA repair. The altered methylation rate of the other genes has already been reported to be related to tumorigenesis, but the low methylation rate of RB1 found in tumors in our sample is different from that so far reported in the literature, suggesting that perhaps hypermethylation of the promoter is not the main event in the inactivation of this gene. Our results suggest that hypermethylation of the promoter region is a very common event in nervous system tumors.

MALDI Imaging Analysis of Neuropeptides in the Africanized Honeybee (Apis mellifera) Brain: Effect of Ontogeny

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Influence of Delivery Method on Neuroprotection by Bone Marrow Mononuclear Cell Therapy following Ventral Root Reimplantation with Fibrin Sealant

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effects of acute and chronic administration of phosphatidylserine on cell proliferation and survival in the dentate gyms of adult and middle-aged rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)