Increase in the quality of life, combined with drug strategies, has been studied as possibilities for improving memory and delaying the onset of neurodegenerative diseases. A previous study published by the group of the authors has shown that microdose lithium and enriched environment can improve memory in both mice and humans. To elucidate this relationship better, this study aimed to evaluate whether the chronic combination of these two strategies could increase healthy aging in Senescence Accelerated Mouse-Prone 8 (SAMP8). Animals were submitted to either one or both of these strategies until the age of 10 months when they were anesthetized and killed and their hippocampus was extracted. The untreated SAMP-8 group exhibited worse memory and reduced neuronal density with greater neurodegeneration and increased amyloid-β plaque density compared with the control group. Moreover, significant alterations in proteins related to long-term potentiation, such as, synaptophysin and brain-derived neurotrophic factor (BDNF), were observed in this group. The strategies used in the study maintained long-term memory, reduced anxiety, and increased neuroprotection. Both strategies were efficient in reducing neurodegeneration and increasing parameters related to memory maintenance. In many experiments, the combination of the two strategies was more effective in improving healthy aging. This study sheds light on the combination of strategies that choose to improve the quality of life and drugs with low side effects. Moreover, it opens perspectives for a new field of study for healthy aging.
Aging is a dynamic and progressive process that begins at conception and continues until death. This process leads to a decrease in homeostasis and morphological, biochemical and psychological changes, increasing the individual’s vulnerability to various diseases. The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases, impairment of the central nervous system and dementias, such as Alzheimer’s disease, whose main risk factor is age, leading to an increase of the number of individuals who need daily support for life activities. Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species, which leads to inflammation, oxidation, cell membrane damage and consequently neuronal death. Also, mitochondrial mutations, which are generated throughout the aging process, can lead to changes in energy production, deficiencies in electron transport and apoptosis induction that can result in decreased function. Additionally, increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells. Recent reports point to the importance of changing lifestyle by increasing physical exercise, improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms. Therefore, this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.
Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein–kinin system (KKS) in Alzheimer’s disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer’s disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and Aβ peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer’s disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein–kinin system plays a beneficial role in Alzheimer’s disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer’s disease.
Background and Purpose Attention training reverses the neurodegeneration and memory loss promoted by infusion of amyloid‐β (Aβ) peptide in rats and increases the density of α7 nicotinic ACh receptors (α7nAChRs) in brain areas related to memory. Hence, we aimed to assess the role of α7nAChRs in the memory recovery promoted by attention training. Experimental Approach C57Bl/6 mice were chronically infused with Aβ, Aβ plus the α7 antagonist methyllycaconitine (MLA), or MLA alone. Control animals were infused with vehicle. Animals were subjected weekly to the active avoidance shuttle box for 4 weeks (attention training). The brain and serum were collected for biochemical and histological analysis. Key Results Aβ caused cognitive impairment, which was reversed by the weekly training, whereas Aβ + MLA also promoted memory loss but with no reversal with weekly training. MLA alone also promoted memory loss but with only partial reversal with the training. Animals infused with Aβ alone showed senile plaques in hippocampus, no change in BDNF levels in cortex, hippocampus, and serum, but increased AChE activity in cortex and hippocampus. Co‐treatment with MLA increased AChE activity and senile plaque deposition in hippocampus as well as reducing BDNF in hippocampus and serum, suggesting a lack of α7nAChR function leads to a loss of neuroprotection mechanisms. Conclusions and Implications The α7nAChR has a determinant role in memory recovery and brain resilience in the presence of neurodegeneration promoted by Aβ peptide. These data support further studies concerning these receptors as pharmacological targets for future therapies.
Com o aumento da longevidade populacional a aplicação de conhecimentos gerontológicostorna-se uma ferramenta de grande valor para promover um envelhecimento saudável. A proximidade da velhice acarreta aumento de doenças crônicas que muitas vezes podem ser debilitantes. Nos últimos anos nosso grupo de pesquisa vem estudando os beneficíos do enriquecimento ambiental e administração de microdoses dos íons de lítio para a melhora da memória de animais e seres humanos, o que pode levar à longevidade com saúde. Postanto o objetivo do projeto foi verificar a efetividade do tratamento com microdoses de lítio, por via oral, em camundonos pertencentes à linhagem que apresenta envelhecimento acelerado (SAMP-8, "senescece-accelerated mouse") combinada ou não com o enriquecimento ambiental, para a promoção do envelhecimento saudável. Os animais SAMR-1 ("senescence-accelerated mouse resistant") foram utilizados como controles dos animais SAMP-8. Os camundongos SAMP-8 foram divididos em quatro grupos: 1) Grupo Controle: sem tratamento e sem estímulação; 2) Grupo Lítio (Li): tratados com 0,25 mg/kg de carbonato de lítio, dissolvidos na água de beber; 3) Grupo Ambiente Enriquecido (AE): colocados diariamente em ambiente enriquecido, constituído por diferentes objetos; 4) Grupo Li+AE: tratados com lítio e colocados em ambiente enriquecido. Ao atingirem 10 meses de idade foi possível observar que os animais SAMP-8 controle tiveram uma diminuição da memória quando comparados aos animais SAMR-1. Além disso, apresentaram menos densidade neuronal, maior área de neurodegeneração, maior densidade de placas senis e diminuição da densidade de sinaptofisina em relação aos aniamis SAMR-1. Os tratamentos por si só promoveram resultados semelhantes. É possível sugerir que as estratégias propostas, combinadas ou não, são benéficas para animais com envelhecimento acelerado, contribuindo assim para a manutenção da memória na velhice.
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