Antihyperlipidemic potential of Cedrus deodara extracts in monosodium glutamate induced obesity in neonatal rats

Objective: To study the antihyperlipidemic effect of Cedrus deodara (C. deodara) against monosodium glutamate (MSG) induced obesity in neonatal rats. Materials and Methods: The studies were carried out on newborn neonatal rats and were injected intraperitoneally with 2 mg/g of MSG on the 2(nd) and 4(th) postnatal days and 4 mg/g on 6(th), 8(th) and 10(th) postnatal days. Ethanolic extract (EE) and acetone extract (AE) of C. deodara was administered in a dose of 100 and 200 mg/kg, p.o./day at the age of 65 days. On day 60 of treatment, body weight, locomotor activity, body temperature, and various biochemical parameters like serum glucose, total cholesterol, triglyceride, and organs weights were recorded. Results: There was a significant reduction in body weight, organs and increased body temperature, locomotor activity after treatment with extracts. C. deodara decreased serum glucose, total cholesterol and triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels and increased high density lipoprotein (HDL) significantly has compared to MSG-control rats. Conclusion: C. deodara extracts exhibited antihyperlipidemic effect and it possesses anti-obesity properties in MSG induced obese rats.

Expression of Sonic Hedgehog During Cell Proliferation in the Human Cerebellum

The regulation of cell proliferation in the external granular layer (EGL) of the developing cerebellum is important for its normal patterning. An important signal that regulates EGL cell proliferation is Sonic hedgehog (Shh). Shh is secreted by the Purkinje cells (PC) and has a mitogenic effect on the granule cell precursors of the EGL. Deregulation of Shh signaling has been associated with abnormal development, and been implicated in medulloblastomas, which are tumors that arise from the cerebellum. Given the importance of the Shh pathway in cerebellum development and disease, there has been no systematic study of its expression pattern during human cerebellum development. In this study, we describe the expression pattern of Shh, its receptor patched, smoothened, and its effectors that belong to the Gli family of transcription factors, during normal human cerebellum development from 10 weeks of gestational age, and in medulloblastomas that represents a case of abnormal cell proliferation in the cerebellum. This expression pattern is compared to equivalent stages in the normal development of cerebellum in mouse, as well as in tumors. Important differences between human and mouse that reflect differences in the normal developmental program between the 2 species are observed. First, in humans there appears to be a stage of Shh signaling within the EGL, when the PC are not yet the source of Shh. Second, unlike in the postnatal mouse cerebellum, expression of Shh in the PC in the postnatal human cerebellum is downregulated. Finally, medulloblastomas in the human but not in patched heterozygote mouse express Shh. These results highlight cross-species differences in the regulation of the Shh signaling pathway.

Early protein malnutrition disrupts cerebellar development and impairs motor coordination

Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin-positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week.

A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats

As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6 h daily/3 d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus amygdala cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased, fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions. (C) 2014 Elsevier B.V. All rights reserved.

The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort.

INTRODUCTION: Recent studies in other European countries suggest that the prevalence of congenital cryptorchidism continues to increase. This study aimed to explore the prevalence and natural history of congenital cryptorchidism in a UK centre. METHODS: Between October 2001 and July 2008, 784 male infants were born in the prospective Cambridge Baby Growth Study. 742 infants were examined by trained research nurses at birth; testicular position was assessed using standard techniques. Follow-up assessments were completed at ages 3, 12, 18 and 24 months in 615, 462, 393 and 326 infants, respectively. RESULTS: The prevalence of cryptorchidism at birth was 5.9% (95% CI 4.4% to 7.9%). Congenital cryptorchidism was associated with earlier gestational age (p<0.001), lower birth weight (p<0.001), birth length (p<0.001) and shorter penile length at birth (p<0.0001) compared with other infants, but normal size after age 3 months. The prevalence of cryptorchidism declined to 2.4% at 3 months, but unexpectedly rose again to 6.7% at 12 months as a result of new cases. The cumulative incidence of "acquired cryptorchidism" by age 24 months was 7.0% and these cases had shorter penile length during infancy than other infants (p = 0.003). CONCLUSIONS: The prevalence of congenital cryptorchidism was higher than earlier estimates in UK populations. Furthermore, this study for the first time describes acquired cryptorchidism or "ascending testis" as a common entity in male infants, which is possibly associated with reduced early postnatal androgen activity.

Isolating single primary rat hippocampal neurons and astrocytes on ultra-thin patterned parylene-C/silicon dioxide substrates

We report here the patterning of primary rat neurons and astrocytes from the postnatal hippocampus on ultra-thin parylene-C deposited on a silicon dioxide substrate, following observations of neuronal, astrocytic and nuclear coverage on strips of different lengths, widths and thicknesses. Neuronal and glial growth was characterized 'on', 'adjacent to' and 'away from' the parylene strips. In addition, the article reports how the same material combination can be used to isolate single cells along thin tracks of parylene-C. This is demonstrated with a series of high magnification images of the experimental observations for varying parylene strip widths and thicknesses. Thus, the findings demonstrate the possibility to culture cells on ultra-thin layers of parylene-C and localize single cells on thin strips. Such work is of interest and significance to the Neuroengineering and Multi-Electrode Array (MEA) communities, as it provides an alternative insulating material in the fabrication of embedded micro-electrodes, which can be used to facilitate single cell stimulation and recording in capacitive coupling mode. © 2010 Elsevier Ltd.

Increased physical activity is not enough to recover astrocytic population from dark-rearing. Synergy with multisensory enrichment is required

10 p.

Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis

Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of the brain inflammatory response during infections and disease. In addition, microglia has a more benign, less explored role as the brain professional phagocytes. Phagocytosis is a term coined from the Greek to describe the receptor-mediated engulfment and degradation of dead cells and microbes. In addition, microglia phagocytoses brain-specific cargo, such as axonal and myelin debris in spinal cord injury or multiple sclerosis, amyloid-beta deposits in Alzheimer's disease, and supernumerary synapses in postnatal development. Common mechanisms of recognition, engulfment, and degradation of the different types of cargo are assumed, but very little is known about the shared and specific molecules involved in the phagocytosis of each target by microglia. More importantly, the functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon, since it eliminates dead cells and induces an anti-inflammatory response. However, phagocytosis can also activate the respiratory burst, which produces toxic reactive oxygen species (ROS). Phagocytosis has been traditionally studied in pathological conditions, leading to the assumption that microglia have to be activated inorder to become efficient phagocytes. Recent data, however, has shown that unchallenged microglia phagocytose apoptotic cells during development and in adult neurogenic niches, suggesting an overlooked role in brain remodeling throughout the normal lifespan. The present review will summarize the current state of the literature regarding the role of microglial phagocytosis in maintaining tissue homeostasis in health as in disease.

Plasticidad postlesional en el sistema visual : estrategias experimentales para su incremento en el adulto

196 p. :il.

Anatomical and developmental patterns of interleukin-2 gene expression in the mouse: analysis of IL-2 expressing cells and partial characterization of interactions involved in mediating IL-2 gene expression in vivo

Interleukin-2 (IL-2) is an important mediator in the vertebrate immune system. IL-2 is a potent growth factor that mature T lymphocytes use as a proliferation signal and the production of IL-2 is crucial for the clonal expansion of antigen-specific T cells in the primary immune response. IL-2 driven proliferation is dependent on the interaction of the lymphokine with its cognate multichain receptor. IL-2 expression is induced only upon stimulation and transcriptional activation of the IL-2 gene relies extensively on the coordinate interaction of numerous inducible and constitutive trans-acting factors. Over the past several years, thousands of papers have been published regarding molecular and cellular aspects of IL-2 gene expression and IL-2 function. The vast majority of these reports describe work that has been carried out in vitro. However, considerably less is known about control of IL-2 gene expression and IL-2 function in vivo.

To gain new insight into the regulation of IL-2 gene expression in vivo, anatomical and developmental patterns of IL-2 gene expression in the mouse were established by employing in situ hybridization and immunohistochemical staining methodologies to tissue sections generated from normal mice and mutant animals in which T -cell development was perturbed. Results from these studies revealed several interesting aspects of IL-2 gene expression, such as (1) induction of IL-2 gene expression and protein synthesis in the thymus, the primary site of T-cell development in the body, (2) cell-type specificity of IL-2 gene expression in vivo, (3) participation of IL-2 in the extrathymic expansion of mature T cells in particular tissues, independent of an acute immune response to foreign antigen, (4) involvement of IL-2 in maintaining immunologic balance in the mucosal immune system, and (5) potential function of IL-2 in early events associated with hematopoiesis.

Extensive analysis of IL-2 mRNA accumulation and protein production in the murine thymus at various stages of development established the existence of two classes of intrathymic IL-2 producing cells. One class of intrathymic IL-2 producers was found exclusively in the fetal thymus. Cells belonging to this subset were restricted to the outermost region of the thymus. IL-2 expression in the fetal thymus was highly transient; a dramatic peak ofiL-2 mRNA accumulation was identified at day 14.5 of gestation and maximal IL-2 protein production was observed 12 hours later, after which both IL-2 mRNA and protein levels rapidly decreased. Significantly, the presence of IL-2 expressing cells in the day 14-15 fetal thymus was not contingent on the generation of T-cell receptor (TcR) positive cells. The second class of IL-2 producing cells was also detectable in the fetal thymus (cells found in this class represented a minority subset of IL-2 producers in the fetal thymus) but persist in the thymus during later stages of development and after birth. Intrathymic IL-2 producers in postnatal animals were located in the subcapsular region and cortex, indicating that these cells reside in the same areas where immature T cells are consigned. The frequency of IL-2 expressing cells in the postnatal thymus was extremely low, indicating that induction of IL-2 expression and protein synthesis are indicative of a rare activation event. Unlike the fetal class of intrathymic IL-2 producers, the presence of IL-2 producing cells in the postnatal thymus was dependent on to the generation of TcR+ cells. Subsequent examination of intrathymic IL-2 production in mutant postnatal mice unable to produce either αβ or γδ T cells showed that postnatal IL-2 producers in the thymus belong to both αβ and γδ lineages. Additionally, further studies indicated that IL-2 synthesis by immature αβ -T cells depends on the expression of bonafide TcR αβ-heterodimers. Taken altogether, IL-2 production in the postnatal thymus relies on the generation of αβ or γδ-TcR^+ cells and induction of IL-2 protein synthesis can be linked to an activation event mediated via the TcR.

With regard to tissue specificity of IL-2 gene expression in vivo, analysis of whole body sections obtained from normal neonatal mouse pups by in situ hybridization demonstrated that IL-2 mRNA^+ cells were found in both lymphoid and nonlymphoid tissues with which T cells are associated, such as the thymus (as described above), dermis and gut. Tissues devoid of IL-2 mRNA^+ cells included brain, heart, lung, liver, stomach, spine, spinal cord, kidney, and bladder. Additional analysis of isolated tissues taken from older animals revealed that IL-2 expression was undetectable in bone marrow and in nonactivated spleen and lymph nodes. Thus, it appears that extrathymic IL-2 expressing cells in nonimmunologically challenged animals are relegated to particular epidermal and epithelial tissues in which characterized subsets of T cells reside and thatinduction of IL-2 gene expression associated with these tissues may be a result of T-cell activation therein.

Based on the neonatal in situ hybridization results, a detailed investigation into possible induction of IL-2 expression resulting in IL-2 protein synthesis in the skin and gut revealed that IL-2 expression is induced in the epidermis and intestine and IL-2 protein is available to drive cell proliferation of resident cells and/or participate in immune function in these tissues. Pertaining to IL-2 expression in the skin, maximal IL-2 mRNA accumulation and protein production were observed when resident Vγ_3^+ T-cell populations were expanding. At this age, both IL-2 mRNA^+ cells and IL-2 protein production were intimately associated with hair follicles. Likewise, at this age a significant number of CD3ε^+ cells were also found in association with follicles. The colocalization of IL-2 expression and CD3ε^+ cells suggests that IL-2 expression is induced when T cells are in contact with hair follicles. In contrast, neither IL-2 mRNA nor IL-2 protein were readily detected once T-cell density in the skin reached steady-state proportions. At this point, T cells were no longer found associated with hair follicles but were evenly distributed throughout the epidermis. In addition, IL-2 expression in the skin was contingent upon the presence of mature T cells therein and induction of IL-2 protein synthesis in the skin did not depend on the expression of a specific TcR on resident T cells. These newly disclosed properties of IL-2 expression in the skin indicate that IL-2 may play an additional role in controlling mature T-cell proliferation by participating in the extrathymic expansion of T cells, particularly those associated with the epidermis.

Finally, regarding IL-2 expression and protein synthesis in the gut, IL-2 producing cells were found associated with the lamina propria of neonatal animals and gut-associated IL-2 production persisted throughout life. In older animals, the frequency of IL-2 producing cells in the small intestine was not identical to that in the large intestine and this difference may reflect regional specialization of the mucosal immune system in response to enteric antigen. Similar to other instances of IL-2 gene expression in vivo, a failure to generate mature T cells also led to an abrogation of IL-2 protein production in the gut. The presence of IL-2 producing cells in the neonatal gut suggested that these cells may be generated during fetal development. Examination of the fetal gut to determine the distribution of IL-2 producing cells therein indicated that there was a tenfold increase in the number of gut-associated IL-2 producers at day 20 of gestation compared to that observed four days earlier and there was little difference between the frequency of IL-2 producing cells in prenatal versus neonatal gut. The origin of these fetally-derived IL-2 producing cells is unclear. Prior to the immigration of IL-2 inducible cells to the fetal gut and/or induction of IL-2 expression therein, IL-2 protein was observed in the fetal liver and fetal omentum, as well as the fetal thymus. Considering that induction of IL-2 protein synthesis may be an indication of future functional capability, detection of IL-2 producing cells in the fetal liver and fetal omentum raises the possibility that IL-2 producing cells in the fetal gut may be extrathymic in origin and IL-2 producing cells in these fetal tissues may not belong solely to the T lineage. Overall, these results provide increased understanding of the nature of IL-2 producing cells in the gut and how the absence of IL-2 production therein and in fetal hematopoietic tissues can result in the acute pathology observed in IL-2 deficient animals.

Efeitos da administração de inibidores de fosfodiesterases na reversão da hiperatividade de camundongos expostos ao etanol no período correspondente ao terceiro trimestre de gestação em humanos

O consumo de etanol durante a gestação é um grave problema de saúde pública. Durante o desenvolvimento, o sistema nervoso é especialmente susceptível aos efeitos tóxicos do etanol e a exposição ao etanol durante este período pode gerar um amplo espectro de distúrbios neurocomportamentais, sendo o mais frequente, a hiperatividade. Recentemente, estudos têm sugerido que distúrbios na plasticidade neuronal podem estar relacionados com a hiperatividade. Os inibidores de PDE são drogas que agem impedindo a degradação de segundos mensageiros celulares como AMPc e GMPc, mantendo a ativação de proteínas quinases e de fatores de transcrição como o CREB, levando a expressão de genes relacionados à plasticidade. Neste trabalho, avaliamos através do teste de campo aberto se a administração de Vinpocetina ou Rolipram (inibidores de PDE) seria capaz de amenizar ou reverter a hiperatividade de camundongos Suíços expostos ao etanol no período correspondente ao terceiro trimestre de gestação humana. Para tanto, foram realizadas duas etapas: na primeira etapa, durante o período neonatal, os animais receberam injeções intraperitoneais de etanol (5g/Kg em solução salina a 25%, no 2, 4, 6 e 8 dias de vida pós-natal - PN2 a PN8) ou de salina, e 4 horas antes do teste comportamental no campo aberto (10 min), em PN30, receberam Vinpocetina (10mg/Kg ou 20mg/Kg diluídas em DMSO ip) ou somente DMSO ip. Na segunda etapa, os animais foram expostos ao etanol ou à salina no período neonatal nas mesmas condições da primeira etapa e no dia do teste comportamental receberam Rolipram (0,5mg/Kg diluídas em DMSO ip ou somente DMSO ip). Posteriormente aos testes, foram coletados o córtex cerebral frontal e o hipocampo dos animais para avaliação dos níveis de AMPc. Os resultados comportamentais indicam que somente o tratamento com Vinpocetina (20mg/Kg) reverteu a hiperatividade de camundongos expostos ao etanol, resultado que não foi observado com o tratamento com Rolipram. Desta forma, a dosagem dos níveis de AMPc foi realizada apenas nos animais que receberam injeção de Vinpocetina (20mg/Kg). A exposição neonatal ao etanol reduziu significativamente os níveis de AMPc no córtex e no hipocampo. O tratamento com Vinpocetina gerou um aumento nos níveis de AMPc no córtex e restaurou estes níveis no hipocampo. Nossos resultados sugerem que a reversão da hiperatividade pelo tratamento com Vinpocetina pode estar associada ao aumento da plasticidade neural induzida por esta droga.

Aspectos evolutivos da depressão pós-parto e fatores associados

A depressão pós-parto (DPP) é uma condição prevalente que afeta globalmente as mulheres puérperas. Uma hipótese evolutiva aborda a depressão, e consequentemente a DPP, como uma resposta proveniente da evolução do comportamento humano ao longo da História, através da seleção natural. A teoria do investimento parental sugere que os pais não investem automaticamente em toda prole; o investimento é direcionado para que o sucesso reprodutivo seja máximo. No caso de os riscos superarem os benefícios reprodutivos, sintomas de depressão se desenvolvem como sinal de alerta. O objetivo do estudo foi identificar fatores associados à DPP que fossem compatíveis com a teoria do investimento parental. Estudo transversal realizado com 811 mães de lactentes até cinco meses de idade, no município do Rio de Janeiro. A presença de DPP foi definida com base no escore da Escala de Edinburgh (EPDS). Fatores potencialmente associados à DPP foram analisados através de regressão logística com ajuste para fatores de confundimento. Os fatores significativamente associados à DPP foram: apoio social inadequado (OR 3,38; IC 95% 2,32-4,94), baixa escolaridade (OR 2,82; IC 95% 1,69-4,70), violência física entre parceiros íntimos na gestação (OR 2,33; IC 95% 1,56-3,47), idade materna inferior a 35 anos (OR 2,20; IC 95% 1,05-4,64), falta de companheiro (OR 1,90; IC 95% 1,16-3,12), internações durante a gestação (OR 1,87; IC 95% 1,12-3,14) e prematuridade do recém-nascido (OR 1,87; IC 95% 1,02-3,42). Em suma, identificamos alguns fatores associados à DPP que podem ser úteis no rastreamento e acompanhamento de mulheres de risco. Alguns dos fatores associados à DPP podem ser explicados através das hipotéses evolutivas contempladas neste estudo. Entretanto, os achados encontrados não são suficientes para esgotar o conhecimento referente a esta questão. Futuras pesquisas devem focar em diferentes abordagens desta condição e acompanhamento das consequências para as mulheres e suas famílias.

Estudo dos efeitos da exposição materna à nicotina na lactação sobre a função da medula adrenal e dos adipócitos de ratos machos e fêmeas

Alterações nutricionais, hormonais e ambientais nos períodos críticos do desenvolvimento como a gestação e/ou lactação podem influenciar a estrutura e a fisiologia de órgãos e tecidos, predispondo ao aparecimento de doenças na vida adulta. Esse fenômeno é conhecido como programação metabólica. O fumo materno na gestação/lactação tem sido associado ao sobrepeso/obesidade na infância e na vida adulta em ambos os sexos. Porém, estudos evidenciam diferenças entre os gêneros em resposta a exposição à nicotina. Já foi demonstrado que muitas mulheres param de fumar na gestação, mas a maioria destas volta a fumar na lactação. Anteriormente, mostramos que machos adultos cujas mães foram expostas à nicotina na lactação, desenvolveram obesidade central, hiperleptinemia e hipotireoidismo. Como a nicotina afeta a função adrenal e como catecolaminas e glicocorticóides têm efeitos bem conhecidos sobre o tecido adiposo, avaliamos a função da medula adrenal e o conteúdo de leptina no tecido adiposo e músculo de machos e fêmeas cujas mães foram expostas à nicotina na lactação. Dois dias pós-parto, implantamos minibombas osmóticas nas ratas lactantes dividas em: NIC infusão de nicotina (6mg/Kg/dia s.c.) por 14 dias, e C infusão de salina pelo mesmo período. Estas lactantes foram divididas de acordo com o sexo das proles. O sacrifício das proles de ambos os sexos ocorreu aos 15 (fim da exposição à nicotina) e 180 dias de vida. Aos 15 dias, os machos da prole NIC apresentaram aumento de MGV absoluta e relativa ao peso corporal (+72% e +73% respectivamente), hiperleptinemia (+35%), hipercorticosteronemia (+67%), maior peso adrenal (+39%), conteúdo de catecolaminas totais (absoluto: +69% e relativo: +41%), embora diminuição da enzima TH (-33%). Quando adultos, os machos programados exibiram maior massa corporal (+10%), MGV absoluta (+47%) e relativa (+33%), além de hiperleptinemia (+41%) e maior conteúdo de leptina no TAV (+23%). Esses animais também apresentaram hipercorticosteronemia (+77%), maior conteúdo de catecolaminas totais absoluto e relativo (+79% e +89% respectivamente) e de TH (+38%) embora tenham menor secreção de catecolaminas in vitro estimulada por cafeína (-19%) e maior expressão do ADRB3 no TAV (+59%). Em relação as fêmeas da prole NIC aos 15 dias de vida, estas apresentaram menor massa corporal (-6%) e hiperleptinemia (+41%) embora sem alteração da MGV. Aos 180 dias, as fêmeas da prole NIC apresentaram menor conteúdo de leptina no TAS (-46%) e maior conteúdo de leptina no músculo solear (+22%) e diminuição da expressão do ADRB3 no TAV (-39%). Concluímos que a nicotina materna afeta ambos, medula adrenal e tecido adiposo de forma gênero dependente, tanto em curto prazo (quando a nicotina está presente no leite materno), quanto em longo prazo (repercussões na vida adulta). De forma geral, as fêmeas da prole NIC apresentam alterações mais discretas do que os machos em ambos os períodos estudados.

Dieta hiperlipídica materna e pós-natal promove remodelamento adverso do fígado, pâncreas e tecido adiposo na prole

A dieta hiperlipídica (high-fat, HF) materna durante a gestação e/ou lactação aumenta a susceptibilidade da prole para o desenvolvimento de doenças crônicas na fase adulta. Verificar a hipótese que a ingestão materna de dieta HF nos períodos críticos de desenvolvimento (gestação e/ou lactação) predispõe à doença não alcoólica do fígado gorduroso e alterações pancreáticas e no tecido adiposo de camundongos machos adultos. Camundongos C57BL/6 fêmeas receberam durante a gestação e/ou lactação dieta padrão (standard chow, SC) ou HF. Filhotes machos foram divididos em cinco grupos: SC provenientes de mães SC; G provenientes de mães HF durante a gestação; L provenientes de mães HF durante a lactação; GL/HF provenientes de mães HF durante a gestação/lactação, mantendo a mesma dieta HF no período pós-natal (do desmame aos 3 meses deidade); GL provenientes de mães HF durante a gestação/lactação trocando a dieta para SC no período pós-natal (do desmame aos 3 meses deidade). Foi analisada ao longo do experimento a massa corporal da prole. No sacrifício (3 meses), o fígado, o pâncreas e a gordura epididimária foram removidos, pesados e processados e o sangue foi coletado para análise bioquímica. Ao nascimento e ao desmame, filhotes GL/HF foram mais pesados (+6% e +44%, p<0,05, respectivamente) que os filhotes SC. Os filhotes G apresentaram resistência à insulina e menor expressão do transportador de glicose no fígado (GLUT-2). A esteatose hepática foi observada nos grupos G, L, GL e principalmente nos filhotes do grupo GL/HF. A expressão hepática da proteína ligante de elementos regulatórios de esteróis (SREBP-1c) estava aumentada nos filhotes G, GL e GL/HF. Os filhotes G, GL e GL/HF apresentaram hipertrofia da ilhota pancreática e dos adipócitos quando comparados com o grupo SC. O consumo de dieta HF durante a gestação mostra-se ser o período mais prejudicial para os filhotes adultos de camundongos. A programação metabólica por dieta HF leva ao remodelamento adverso do fígado, do pâncreas e do tecido adiposo

Efeitos da programação por nicotina durante a lactação nos níveis de comportamentos associados à ansiedade, busca por novos estímulos e aprendizagem/memória em ratos Wistar adolescentes e adultos

A exposição materna à nicotina durante a lactação em ratos programa para hiperleptinemia e hipotireoidismo na prole adulta. Alterações nos níveis desses hormônios alteram o comportamento. Por isso, resolvemos investigar os efeitos comportamentais a curto e a longo prazo da programação neonatal pela nicotina em ratos Wistar. Foram implantadas minibombas em ratas lactantes contendo nicotina (NIC = 6mg/Kg/Dia) ou uma solução com uma concentração equivalente de solução salina (CON) do 2o dia ao 19o dia de vida pós natal. Sessenta e dois ratos NIC e 48 CON foram testados de acordo com o seguinte protocolo: 1) Em PN30 ou PN75 foram avaliados os níveis de ansiedade no labirinto em cruz elevado (LCE). Entradas em cada área do labirinto (braços abertos e fechados e centro) foram gravadas por um período de 10 minutos; 2) Uma hora após, os animais foram testados no campo vazado (CV) para analisarmos o comportamento de busca por novos estímulos. Os animais tinham 10 minutos para explorar o aparelho. O número de orifícios explorados foi anotado. 3) Em PN31-35 ou PN76-80 o animal foi submetido ao labirinto aquático radial de oito braços (LAROB) para avaliarmos a memória e o aprendizado. Cada animal foi testado 4 vezes por dia durante 5 dias consecutivos sendo a plataforma mantida no mesmo braço durante os 4 primeiros dias e trocada no quinto dia. Eles tinham 2 minutos para encontrar a plataforma de escape. A latência para encontrar a plataforma foi anotada. O percentual de tempo gasto no braço aberto no LCE para os animais NIC em PN30 (6,41,1 %) foi significativamente (ANOVA: P=0,024) menor que o grupo controle PN30 (9,91,4 %). O percentual de entradas no braço aberto foi significativamente menor (ANOVA: P=0,04) para os animais do grupo NIC em PN30 (32,42,9 %) quando comparados com o grupo controle PN30 (38,51,8 %). Não foi observada diferença (ANOVA: P>0,1) entre os grupos no número de entradas no braço fechado para as duas idades. Para o CV não houve diferença entre os grupos para as duas idades (ANOVA: P>0,1). No LAROB, os animais PN75 NIC (27424 s) tiveram uma diminuição significativa (ANOVA: P<0,006) na latência para encontrar a plataforma quando comparado ao grupo controle PN75 nos 4 primeiros dias (41045 s), não havendo diferença no 5o dia. Não houve diferença em PN30 (ANOVA:P>0,1). A programação neonatal pela nicotina resultou em um efeito a curto prazo no aumento dos níveis de ansiedade na adolescência. Não foi observada diferença no comportamento de busca por novos estímulos. Entretanto a programação neonatal por nicotina resultou em um efeito a longo prazo no comportamento-cognitivo observado pelo melhor desempenho na memória/aprendizado quando adulto.