L'exercici té efectes neuroprotectors en la malaltia d'Alzheimer

L'exercici físic voluntari té un efecte protector i terapèutic contra l'Alzheimer: millora les funcions sinàptiques neuronals, l'aprenentatge i la memòria, la funció sensoriomotora i l'ansietat. Així ho demostra un experiment realitzat sobre models animals, del qual són autors un equip d'investigadors de l'Institut d'Investigacions Biomèdiques de Barcelona (CSIC-IDIBAPS), de la UAB, de la Universitat Pablo Olavidede Sevilla i de la Universitat de Califòrnia, i que s'ha publicat a la revista Journal of Alzheimer's Disease. La recerca forma part d'un projecte més ampli d'estimulació ambiental en la malaltia d'Alzheimer, coordinat per la investigadora de l'Institut de Neurociències i professora del Departament de Psiquiatria i Medicina Legal de la UAB Lydia Giménez-Llort.El ejercicio físico voluntario tiene un efecto protector y terapéutico contrae l Alzheimer: mejora las funciones sinápticas neuronales, el aprendizaje y la memoria, la función sensoriomotora y la ansiedad. Así lo de muestraun experimento realizado sobre modelos animales, del que son autores un equipo de investigadores de Instituto de Investigaciones Biomédicas de Barcelona (CSIC-IDIBAPS), de la UAB, de la Universidad Pablo Olavide de Sevilla y la Universidad de California. La investigación se ha publicado en el Journal of Alzheimer's Disease y forma parte de unproyecto más amplio de estimulación ambiental en la enfermedad de Alzheimer, coordinado por la investigadora del Instituto de Neurociencias y profesora del Departamento de Psiquiatría y Medicina Legal de la UAB Lydia Giménez-Llort.Voluntary physical exercise has a protective and therapeutic effect against Alzheimer's disease by improving synaptic functions between neurons, learning and memory, sensory-motor functions and less anxiety. These are the results of a study carried out with animal models by are search team from the Barcelona Institute of Biomedical Research (CSIC-IDIBAPS), Universitat Autònoma de Barcelona, Universidad Pablo de Olavide, Seville, and University of California, and published in the Journal of Alzheimer's Disease. The research forms part of a larger project on environmental stimulation in Alzheimer's disease, coordinated by lecturer Lydia Giménez-Llort from the UAB Department of Psychiatry and Legal Medicine

Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19) : A Translational Neuroscience Approach

The impact of COVID-19 on the elderly is devastating, and nursing homes are struggling to provide the best care to the most fragile. The urgency and severity of the pandemic forces the use of segregation in restricted areas and confinement in individual rooms as desperate strategies to avoid the spread of disease and the worst-case scenario of becoming a deadly trap. The conceptualization of the post-COVID-19 era implies strong efforts to redesign all living conditions, care/rehabilitation interventions, and management of loneliness forced by social distance measures. Recently, a study of gender differences in COVID-19 found that men are more likely to suffer more severe effects of the disease and are over twice as likely to die. It is well-known that dementia is associated with increased mortality, and males have worse survival and deranged neuro-immuno-endocrine systems than females. The present study examines the impact of long-term isolation in male 3xTg-AD mice modeling advanced stages of Alzheimer's disease (AD) and as compared to age-matched counterparts with normal aging. We used a battery of ethological and unconditioned tests resembling several areas in nursing homes. The main findings refer to an exacerbated (two-fold increase) hyperactivity and emergence of bizarre behaviors in isolated 3xTg-AD mice, worrisome results since agitation is a challenge in the clinical management of dementia and an important cause of caregiver burden. This increase was consistently shown in gross (activity in most of the tests) and fine (thermoregulatory nesting) motor functions. Isolated animals also exhibited re-structured anxiety-like patterns and coping-with-stress strategies. Bodyweight and kidney weight loss were found in AD-phenotypes and increased by isolation. Spleen weight loss was isolation dependent. Hippocampal tau pathology was not modified, but asymmetric atrophy of the hippocampus, recently described in human patients with dementia and modeled here for the first time in an animal model of AD, was found to increase with isolation. Overall, the results show awareness of the impact of isolation in elderly patients with dementia, offering some guidance from translational neuroscience in these times of coronavirus and post-COVID-19 pandemic. They also highlight the relevance of personalized-based interventions tailored to the heterogeneous and complex clinical profile of the individuals with dementia and to consider the implications on caregiver burden

Confinement and the Hatred of Sound in Times of COVID-19 : A Molotov Cocktail for People With Misophonia

Forced strict confinement to hamper the COVID-19 pandemic seriously affected people suffering from misophonia (M+) and those living with them. Misophonia is a complex neurophysiological and behavioral disorder of multifactorial origin, characterized by an intense physiological and emotional response produced by intolerance to auditory stimuli of the same pattern, regardless of physical properties. The present work studied the secondary impact that strict confinement caused in 342 adults (224 women: 118 men) regularly attending a medical psychological center in Barcelona. Misophonia, usually underdiagnosed, showed a prevalence of 35%, the same for women (37%) than men (31%). A retrospective analysis using a physical-psychological-social inventory of 10 variables evaluated the number of individuals that during confinement and self-confinement (March 11 - June 29, 2020) canceled (mostly M-) and/or requested a therapeutic intervention, the reasons for their request, and the strategies they used to self-manage the situation. Ten main variables indicated that the confinement exponentially increased the effects of misophonia compared with results from the same individuals during the last quarter of 2019. Most people diagnosed with misophonia continued with tele-assistance during the confinement because of this impact's self-concern. Besides the impacts as part of the general population, M+ also developed different symptoms causing significant personal, social, and job/occupational imbalance, as compared to M-. Health, fears, conflicts with neighbors, study-related difficulties were outstanding reasons for consultations. The LSB-50 test for 'Psychological and Psychosomatic Symptoms' applied to M+ revealed the increase of 8 of 9 items of this psychopathological test. Sleep disorders (coronasomnia), hostility, depression, and somatization were more severe than in previous assessments. Women presented the worst psychological and psychosomatic states (eight out of nine, as compared to one out of nine in males). The study unveiled the complex physical-psychological-social burden, the need for dissemination and a gender perspective to understand the secondary impact of COVID-19 pandemic on the mental health of the population with misophonia. The results also show that in this new COVID era people suffering from misophonia need to develop coping strategies addressing modifiable risk and protective factors. They deserve familial/social comprehension, stronger clinical support and a gender medicine perspective

PasoDoble, a Proposed Dance/Music for People With Parkinson's Disease and Their Caregivers

Managing the heterogeneity of Parkinson's disease symptoms and its progressive nature demands strategies targeting the hallmark disrupted neurotransmission but also the comorbid derangements and bolstering neuroprotection and regeneration. Strong efforts are done to find disease-modifying strategies, since slowing disease progression is not enough to hamper its burden and some motor symptoms are resistant to dopamine-replacement therapy. The inclusion of non-pharmacological strategies can provide such a multitarget umbrella approach. The silent long-term biological process that precedes the clinical onset of disease is a challenge but also an opportunity to reinforce healthy lifestyle known to exert preventive/therapeutic effects. These non-pharmacological strategies are foreseen as able to reduce the prevalence and the global impact of long-term diseases demanding strong management of patient-caregiver quality of life. In this regard, European guidelines for Parkinson's disease recommend physical-related activities such as aerobic exercise and dancing known to improve functional mobility and balance in patients. Here, we propose "PasoDoble," a novel dance/music patient-caregiver intervention with additional preventive value. The rationale is founded on evidence-based therapeutic benefits of dance/music therapy and the singular features of this widely extended Hispanic dance/music targeting motor symptoms, mood/cognition, and socialization: (i) As a dance, an easy and simple double-step pattern (back-and-forward and lateral movements) that evolves from a spontaneous individual dance to a partnered dancing, performed in social groups and involving dancing-figures of increasing complexity; (ii) "PasoDoble," as a music that can be sung, has musical rhythmicity with high groove and familiarity that will help to synchronize the steps to the rhythm of music; (iii) Widely extended (Spain, Mexico, Puerto Rico, Colombia, and USA) and easy-to-learn for others. As a regular dancing "PasoDoble" can improve and preserve function, mood and socialization, as an intervention the method is structured to improve gait and balance; facilitate movement, reaching and grasping; muscle power and joint mobility; reduce of risk of falls, and increase of aerobic capacity. Finally, this easy-to-implement into patient care and free-living environments (elderly social centers, home care) rehabilitation programs can promote positive emotions and self-esteem, with added general improvement of social attachment and recognition, thus improving the quality of life of patient-caregiver

Digging Signatures in 13-Month-Old 3xTg-AD Mice for Alzheimer's Disease and Its Disruption by Isolation Despite Social Life Since They Were Born

The severity of this pandemic's scenarios will leave significant psychological traces in low resistant and resilient individuals. Increased incidence of depression, anxiety, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder has already been reported. The loss of human lives and the implementation of physical distance measures in the pandemic and post-COVID scenarios may have a greater impact on the elderly, mostly in those with dementia, as OCD and other neuropsychiatric symptoms (NPS) are quite prevalent in this population. Modeling NPS in animals relies in neuroethological perspectives since the response to new situations and traumatic events, critical for survival and adaptation to the environment, is strongly preserved in the phylogeny. In the laboratory, mice dig vigorously in deep bedding to bury food pellets or small objects they may find. This behavior, initially used to screen anxiolytic activity, was later proposed to model better meaningless repetitive and perseverative behaviors characteristic of OCD or autism spectrum disorders. Other authors found that digging can also be understood as part of the expression of the animals' general activity. In the present brief report, we studied the digging ethograms in 13-month-old non-transgenic and 3xTg-AD mice modeling normal aging and advanced Alzheimer's disease (AD), respectively. This genetic model presents AD-like cognitive dysfunction and NPS-like phenotype, with high mortality rates at this age, mostly in males. This allowed us to observe the digging pattern's disruption in a subgroup of 3xTg-AD mice that survived to their cage mates. Two digging paradigms involving different anxiogenic and contextual situations were used to investigate their behavior. The temporal course and intensity of digging were found to increase in those 3xTg-AD mice that had lost their "room partners" despite having lived in social structures since they were born. However, when tested under neophobia conditions, this behavior's incidence was low (delayed), and the temporal pattern was disrupted, suggesting worsening of this NPS-like profile. The outcomes showed that this combined behavioral paradigm unveiled distinct features of digging signatures that can be useful to study these perseverative behaviors and their interplay with anxiety states already present in the AD scenario and their worsening by naturalistic/forced isolation

Sounds of Silence in Times of COVID-19 : Distress and Loss of Cardiac Coherence in People With Misophonia Caused by Real, Imagined or Evoked Triggering Sounds

The extreme, unprecedented situations in the current COVID-19 pandemic are risk factors for psychosocial stress for the entire population. However, strict confinement had a particular impact on people suffering from misophonia and their families. Misophonia is a condition in which hearing certain sounds triggers intense anger, disgust and even severe autonomic nervous system responses. This prospective cohort study examined the impact of strict confinement (Spain, March 14-June 21, 2020) on a sample of 24 people (16 women and eight men) who had been diagnosed with moderate to extreme misophonia and were regularly attending a medical psychology center in Barcelona. The 3-month period of confinement caused general emotional maladjustment, distress, and a transitory crisis. Long-term biomonitoring of their heart variability rate (HRV) enabled to identify a significant increase in physiological arousal after the confinement period, which had already been recorded in a loss of cardiac coherence under basal rest/relaxation conditions. Certain auditory stimuli triggered adverse responses, lowered HRV scores, and an increased stress level and heart rate. Loss of cardiac coherence in their responses to these auditory stimuli (triggering mouth, nose and other sounds), as well as to non-triggering mouth, nose and other sounds was increased when compared to two assessments performed during the previous year. Despite the limited sample size, sex differences were observed in the incidence. Loss of cardiac coherence worsened with the severity of the misophonia. Most importantly, imagined or evoked triggering sounds, as well as real ones, were enough to cause the aversive responses, as displayed by the increased loss of cardiac coherence with respect to the at-rest basal level. A semi-structured interview revealed the exceptional nature of the situations, increased hyper-sensorial sensitivity, fear of being infected with or dying from COVID-19, the patients' coping strategies, and the difficulties and constraints they faced. Finally, the article gives recommendations for better management of misophonia. Improved knowledge of this disorder would help address the current lack of health and social care, hopefully preventing this shortfall's impact on social and affective relationships, which are particulary important for well-being now and in the coming periods of physical distancing measures

Sexual Dimorphism in the Behavioral Responses and the Immunoendocrine Status in d-Galactose-Induced Aging

Altres ajuts: R.B.C. received a predoctoral grant FI-DGR (2012FI_B1 00198) from Secretaria d' Universitat i Recerca del Departament d'Economia i Coneixement de la Generalitat de Catalunya.For almost 20 years, chronic systemic d-galactose, a monosaccharide abundantly present in milk products, fruits, and vegetables, has been used as a tool to achieve models of accelerated aging. Its neurotoxicity, induced by abnormal accumulation of reactive oxygen species and advanced glycation end products, has been widely reported. However, behavioral outcomes are still controversial and little is known about sex-dependent vulnerability. We performed a comprehensive behavioral and multifunctional screening of the chronic effects of low (50 mg/kg) and high (100 mg/kg) doses of d-galactose in 6-month-old male and female gold-standard C57BL/6 mice. Twelve classical tests with convergent validity analyzed sensorimotor, emotional and cognitive domains, indicating the existence of thresholds of response. Distinct vulnerability patterns were found in a selective sex- and dose-dependent manner. In males, d-galactose induced sensorimotor impairment and immunoendocrine senescence, but the low dose resulted in improved learning and memory. Oppositely, d-galactose-treated females exhibited a dose-dependent worse motor and spatial learning, but improved memory. Behavioral outcome items point at distinct neuronal substrates underlying the functional capacity of d-galactose-treated animals to meet task-dependent performance demands. They support that males and females can be regarded as two exceptional natural scenarios to study the functional interplay in the cross talk of homeostatic networks in aging

Sex-dependent signatures, time frames and longitudinal fine-tuning of the marble burying test in normal and ad-pathological aging mice

Altres ajuts: This work was funded by UAB-GE-260408 to L.G.-L.It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.6.The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer's disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex-and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice

Crosstalk of Alzheimer's disease-phenotype, HPA axis, splenic oxidative stress and frailty in late-stages of dementia, with special concerns on the effects of social isolation : A translational neuroscience approach

Altres ajuts: Envellir bé-Saber envejecer-Healthy Aging.org Memorial Mercedes Llort Sender 2022/81/24091941/02Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer's disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic-pituitary-adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD

Impact of Behavioral Assessment and Re-Test as Functional Trainings That Modify Survival, Anxiety and Functional Profile (Physical Endurance and Motor Learning) of Old Male and Female 3xTg-AD Mice and NTg Mice with Normal Aging

Altres ajuts: UAB-GE-260408; Memorial Mercedes Llort Sender 2021/80/09241941.8Longitudinal approaches for disease-monitoring in old animals face survival and frailty limitations, but also assessment and re-test bias on genotype and sex effects. The present work investigated these effects on 56 variables for behavior, functional profile, and biological status of male and female 3xTg-AD mice and NTg counterparts using two designs: (1) a longitudinal design: naïve 12-month-old mice re-tested four months later; and (2) a cross-sectional design: naïve 16-month-old mice compared to those re-tested. The results confirmed the impact as (1) improvement of survival (NTg rested females), variability of gait (3xTg-AD 16-month-old re-tested and naïve females), physical endurance (3xTg-AD re-tested females), motor learning (3xTg-AD and NTg 16-month-old re-tested females), and geotaxis (3xTg-AD naïve 16-month-old males); but (2) worse anxiety (3xTg-AD 16-month-old re-tested males), HPA axis (3xTg-AD 16-month-old re-tested and naïve females) and sarcopenia (3xTg-AD 16-month-old naïve females). Males showed more functional correlations than females. The functional profile, biological status, and their correlation are discussed as relevant elements for AD-pathology. Therefore, repetition of behavioral batteries could be considered training by itself, with some variables sensitive to genotype, sex, and re-test. In the AD-genotype, females achieved the best performance in physical endurance and motor learning, while males showed a deterioration in most studied variables