SummaryModern stereological methods have been used to make unbiased estimates of the total number of synapses in the striatum radiatum of the hippocampal CA1 region of five rabbits. The approach used involved a two stage analysis and is generally applicable to all parts of the nervous system. During the first stage of the analysis, the reference volume was estimated by point counting, at the light microscope level, according to the Cavalieri principle. During the second stage, the numerical density of synapses was estimated with disectors at the electron microscopic level. The total number of synapses was calculated as the product of the numerical density and the volume of the region. The sampling with points and disectors was carried out in all three dimensions of the entire CA1 region in a manner that ensured that all parts of the region and all synapses within it had equal probabilities of being sampled. An analysis of the precision of the estimate of total synapse number has been performed in terms of the variances of volume and synaptic numerical density at different levels of sampling, i.e. at the level of points, sections, individual animals and group of animals. Detailed descriptions of the procedures used to estimate the total number of synapses, evaluate the precision of the estimates, and optimize the sampling scheme are provided.

Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments.

Background Since pharmacological treatments to manage dementia remain controversial, development of non-pharmacological alternatives to limit adverse effects of dementia is urgently needed. Passive exercise in a multisensory environment (Therapeutic Motion Simulation (TMSim, Whole Body Vibration (WBV) and a combination (TMSim + WBV)) is proposed to be such a non-pharmacological alternative. This study primarily aimed to investigate the effects of these different forms of passive exercise on Quality of Life (QoL) and Activities of Daily Living (ADLs) of inactive institutionalized patients with dementia. The secondary aim was to assess the effects on cognitive and physical function. Methods In this randomized controlled trial 120 inactive institutionalized persons with dementia (age 85.3 ± 6.8 years, 64.5% female, 59.2% walking aid/wheelchair users, mini mental state examination 12.9 ± 6.6) were assigned to TMSim, WBV, TMSim + WBV or a control group (regular care) The passive exercise groups followed a six-week intervention program consisting of four 4–12 minute sessions a week. QoL, ADLs (proxy-report questionnaires), cognitive and physical function (performance based tests) were measured at baseline, after 6 weeks of intervention, and 2 weeks after the intervention had ended. Results Outcome measures did not differ between groups at baseline. No consistent effects of passive exercise on QoL, ADLs, cognitive and physical function were observed after six weeks of intervention or during follow-up. Conclusion In the current setting passive exercise did not affect any of the outcomes measures. This may be due to the short intervention period, limited sensitivity to change of the assessment instruments in this specific vulnerable population or short lasting effects of the interventions. Future research into passive exercise should consider measuring acute and short term effects as well as longer intervention periods looking into alternative outcome measures (e.g. seated balance and behavioral and psychological symptoms of dementia).

The concept of resilience, i.e., the capacity of a system to bounce back after a stressor, is gaining interest across many fields of science, policy and practice. To date, resilience research in people with cognitive decline has predominantly addressed the early stages of decline. We propose that: (1) resilience is a relevant concept in all stages of cognitive decline; and (2) a socioecological, multisystem perspective on resilience is required to advance understanding of, and care and support for people with cognitive decline and their support networks. We substantiate our position with literature and examples. Resilience helps to understand differences in response to risk factors of (further) cognitive decline and informs personalised prevention. In a curative context, interventions to strengthen resilience aim to boost recovery from cognitive decline. In care for people with dementia, resilience focused interventions can strengthen coping mechanisms to maintain functioning and wellbeing of the individual and their support network. A good example of improving resilience in the social and policy context is the introduction of age-friendly cities and dementia-friendly communities. Good care for people with cognitive decline requires a health and social care system that can adapt to changes in demand. Given the interdependency of resilience at micro-, meso- and macro-levels, an integrative socioecological perspective is required. Applying the concept of resilience in the field of cognitive decline opens new horizons for research to improve understanding, predicting, intervening on health and social care needs for the increasing population with cognitive decline.

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