This study examines the age-associated changes in noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) in different brain areas of rats. DA and DOPAC concentrations in striatum increased at third month of age, remaining without significant variations until 12th month of age, and decreasing in 24-month-old rats. DA concentration dropped in hippocampus, amygdala and brainstem of 24-month-old-rats, whereas DOPAC levels decreased only in hippocampus. These changes suggest an age-dependent deficit of the dopaminergic system, presumably related to a reduced number/activity of DA nigrostriatal and mesolimbic neurons. An age-induced decline in NA content was found in the pons-medulla, the area containing NA neuronal bodies. Concentrations of 5-HT were reduced with aging in frontal cortex, showing a tendency to decrease in all brain areas examined. The increased 5-HIAA/5-HT ratio found in frontal cortex, amygdala and striatum suggests an age-related decreased synthesis and an accelerated 5-HT metabolism. The 5-HIAA content decreased in brainstem of the oldest rats. These findings point to a selective impairment of nigrostriatal and mesolimbic DA in aging rats, whereas reductions in NA were restricted to cell bodies region and 5-HT showed changes of different extent in areas of terminals and neuronal cell bodies.

We used intracerebral microdialysis to study the role of raphe and presynaptic serotonin (5-HT) autoreceptors in the effect of the selective 5-HT reuptake inhibitor, paroxetine, on 5-HT release from ventral hippocampus of anaesthetised rats. In addition, we have tested the ability of pindolol, a non-selective beta-adrenergic/5-HT(1A) receptor antagonist, to alter the response of hippocampal 5-HT to paroxetine. Doses of paroxetine with maximal effects were near to three-fold less effective when administered systemically than after local infusion at increasing extracellular 5-HT in ventral hippocampus. Moreover, systemic paroxetine treatment resulted in a marked decrease of the extracellular 5-HT in the hippocampus when 5-HT reuptake was blocked with paroxetine 3 microM applied locally, thereby evidencing that systemic treatment induced a decrease of 5-HT release in the neuronal terminal. A similar drop was observed when paroxetine 3 microM was perfused into the median raphe, a region that contains the cell bodies of the neurons innervating the ventral hippocampus. Racemic (+/-)-pindolol (10 mg/kg, s.c.) completely blocked the paroxetine-induced decrease in 5-HT release from rat hippocampus. In addition, the infusion into median raphe of (-)-pindolol, the isoform with highest antagonist activity, at concentrations of 10 microM and 100 microM was able to partially block the decrease of hippocampal 5-HT release after systemic paroxetine. However, perfusion of (-)-pindolol into the hippocampus was without effect on local 5-HT release. These data suggest that pindolol acts preferentially through the blockade of somatodendritic 5-HT(1A) autoreceptors to restore the decline in 5-HT outflow in rat forebrain following systemic administration of selective 5-HT reuptake inhibitors.

No abstract

IntroductionThe European population is aging rapidly. The number of Europeans aged over sixty-five will double in the next fifty years. Active and healthy aging is a societal challenge shared by all European countries, but also an opportunity. The World Health Organization indicated that frailty has become an indicator of lack of successful aging. Therefore, identification of frail elderly is becoming important. However, there are many different screening tools that are currently used to identify frailty. The optimal test should have the capacity to easily identify from the community-dwelling population, those older people at risk of adverse outcomes. During the past years, gait speed has been repeatedly reported as an appealing instrument as a screening tool to detect frailty.MethodsSystematic review of literature on gait speed as predictor of frailty was performed.ResultsA total of 992 articles were retrieved from the literature search and only eleven studies met the inclusion criteria. Frailty is a common geriatric syndrome, characterized by decreased reserve and increased vulnerability to adverse outcomes, including falls, hospitalization, institutionalization and death. Despite frailty is being increasingly recognized in the literature, there is a paucity of direct evidence to guide interventions to reduce frailty. Many single and composite tools to detect the frailty have been proposed but none is consensual, most are time-consuming while evaluating different domains of impairments, and many are not validated. Gait speed seems to be a single, reliable, valid, sensitive, cheap, quick and simple tool that identifies frailty people. However, the way to perform the test parameters vary widely, influencing interpretations of physical performance.ConclusionsThe evidence recommends to detect frailty in people in order to achieve an active and healthy ageing. Gait speed could be a suitable predictor to identify frailty although this systematic review found many differences between the gait speed protocols used in clinical practice. It is necessary to establish a standard protocol of gait speed agreed by experts in the area on frailty to be implemented with success in clinical practice.