Abstract

Aging is a multifactorial phenomenon that results in several changes at cellular and molecular levels and is considered the main risk factor for some neurodegenerative diseases. Several evidence show the participation of the kallikrein-kinin system (KKS) in neurodegeneration and this system has been associated with inflammation and immunogenic responses in the central and peripheral systems by the activation of the B1 and B2 receptors. Previous work by our group showed that bradykinin (BK) and the B2 receptor played a possible role in neuroprotection. Therefore, the objective of this study was to evaluate the participation of B2 receptors in cell viability, neuroinflammatory response and neuroplasticity in organotypic hippocampal cultures (OHCs) of 6- and 12-month-old mice. It was observed that activation of the B2 receptor by bradykinin decreased the inflammatory response and increased plasticity in 12-month-old slices. Conversely, there was an increase in the inflammatory response and a decrease in neural plasticity in the 6-month-old slices. In both ages, an increase in cell viability was observed. This data suggests that the function of the kinin B2 receptor in the hippocampus is modulated by age, providing neuroprotective action in old age.

Highlights

  • It is a fact that the global population has been passing through a significant demographic transition

  • Considering that an increase in inflammation is observed during the aging process (Franceschi and Campisi, 2014), the aim of this study was to evaluate the participation of the BKB2R in cell viability and inflammatory response in organotypic hippocampal cultures (OHCs) from mature adult and middle-aged mice (6 and 12 months old, respectively)

  • Unlike most research groups that use animals up to 10 days old to set hippocampal organotypic cultures, whose young neurons have greater plasticity and resistance to survive under culture conditions, in the present study the hippocampal slices were from 6-and 12-month-old animals

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Summary

Introduction

It is a fact that the global population has been passing through a significant demographic transition. Many societies are no longer predominantly formed by young people and adults; they are turning into societies composed of a larger proportion of older people (Custodio et al, 2017). This data demonstrates an improvement in life expectancy, it points to the possibility of an alarming increase in the number of people affected by diseases related to aging, such as Alzheimer’s disease (AD; Wimo et al, 2017). The aging process is associated with a progressive decline in responsiveness and ability to adapt to environmental challenges. This decline in functions includes deficits in the central nervous system (CNS), with structural and biochemical alterations, repair deficiency, the formation of senile plaques and neurofibrillary tangles, which leads to macroscopic and microscopic changes culminating in neuronal death (Custodio et al, 2017).

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