Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post-ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal

Representações sociais de saúde bucal entre mães no meio rural de Itaúna (MG), 2002 A social representation study of oral health among mothers in rural areas, Itaúna (MG), 2002

Análise das representações sociais sobre o processo saúde-doença bucal entre 29 mães de escolares residentes no meio rural de Itaúna, em 2002. As entrevistas semi-estruturadas foram transcritas e a análise de conteúdo foi desenvolvida. A análise mostra que as representações sociais sobre saúde-doença estão vinculadas à alimentação e utilização de serviços médicos. Em relação ao processo saúde-doença bucal, identifica-se um discurso associado às normas odontológicas de higiene e dieta. A cárie dentária é vista como uma experiência inevitável, mas a perda dentária, não. Apesar de as condições materiais de vida no meio rural dificultarem a adoção de práticas consideradas favoráveis à saúde bucal, essas mulheres são cobradas em relação ao trabalho de cuidar dos filhos. Essa vivência contraditória causa sentimentos negativos (culpa) e, como conseqüência, queda na qualidade de vida nessa população. Na realidade de vida das entrevistadas, verifica-se que, apesar de as mesmas apresentarem informações sobre o cuidado bucal e desejarem "cuidar dos filhos direito", uma complexa rede de fatores sociais, econômicos, culturais etc., não favorece a promoção de saúde. O planejamento das ações de saúde bucal coletiva deveria levar em consideração não somente dados epidemiológicos quantitativos, mas também as representações sociais sobre saúde bucal.<br>The study evaluated social representation on oral health-illness process between 29 scholarship's mothers in rural areas from Itaúna, in 2002. Semi-structured interviews were transcripted and content analysis was developed. The results have showed that social representation of health-illness was associated with food intake and medical service utilization. Discourse on oral health-illness process was related to dental hygiene and diet rules. Dental caries were an inevitable experience, but tooth loss was not. Despite material conditions of life in rural area have not enabled favorable oral health practices, these mothers were considered responsible for their children oral health care. This contradicted life has caused negative feelings (as guilty) and, consequently, bad quality of life. Respondents have had information about oral home care and they desired to "take care of children well". However, a complex net of social, economic and cultural factors has not favored health promotion. Planning public oral health actions should take in account not only quantitative epidemiological data but social representation of oral health