RESUMO
The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.
Assuntos
Eixo Encéfalo-Intestino , Encéfalo , Disfunção Cognitiva , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/microbiologia , Disfunção Cognitiva/prevenção & controle , Humanos , Feminino , Animais , Efeitos Tardios da Exposição Pré-Natal/etiologia , Melatonina/administração & dosagem , Encéfalo/crescimento & desenvolvimento , Neurogênese , Antioxidantes/administração & dosagem , Probióticos/administração & dosagemRESUMO
Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.
Assuntos
Concussão Encefálica , Disfunção Cognitiva , Hipocampo , Transtornos da Memória , Doenças Neuroinflamatórias , Estresse Oxidativo/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Memória Espacial/fisiologia , Fatores Etários , Animais , Concussão Encefálica/complicações , Concussão Encefálica/imunologia , Concussão Encefálica/metabolismo , Concussão Encefálica/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/imunologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/fisiopatologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Systemic inflammation is known as a risk factor of cognitive decline. OBJECTIVE: To investigate the effects of propolis on cognitive decline and systemic inflammation in elderly people living at high altitude. METHODS: Sixty participants (average 72.8 years) living at altitude (2,260 meters) were randomized to receive propolis (0.83âg, nâ=â30) or placebo (nâ=â30) for 24 months. Cognitive outcomes were assessed using MMSE and serum cytokine levels were measured for 24 months in a double-blind study. RESULTS: MMSE scores were 26.17 at baseline and 23.87 at 24 months in placebo group. Compared to placebo group, improvements of MMSE scores were significant in propolis-treated subjects (pâ=â0.007) with a response emerging over time (time points×group interaction, pâ=â0.016). In addition, the serum IL-1ß and IL-6 levels were significantly different across treatments (pâ<â0.0001) showing upward and downward trends in placebo- and propolis-treated subjects, respectively (pâ<â0.0001). Serum levels of TNF-α were not significantly different across treatment (pâ=â0.0528) but with a response emerging over time (time points×group interaction, pâ=â0.016). In contrast, serum levels of TGFß1 were significantly different across treatments (pâ<â0.0001) showing downward and upward trends in placebo- and propolis-treated subjects, respectively. Serum levels of IL-10 were significant for the effect of groups (pâ=â0.0411). Furthermore, MMSE scores correlated with the decrease in IL-1ß and the increase in TGFß1 in serum. CONCLUSION: Elderly people living at high altitude developed to MCI in 24 months with exacerbation of systemic inflammation. Ingestion of propolis (>12 months) protected against cognitive decline after systemic inflammation was reduced.
Assuntos
Altitude , Anti-Inflamatórios não Esteroides/uso terapêutico , Apiterapia , Disfunção Cognitiva/prevenção & controle , Inflamação/tratamento farmacológico , Própole/uso terapêutico , Idoso , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/psicologia , Masculino , Testes de Estado Mental e Demência , Resultado do TratamentoRESUMO
To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.