Influence of maternal experience on behavioral response to the maternal separation stress in mother rats: Preliminary results

Fil: Aguggia, J. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Suárez, M. M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Rivarola, M. A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Pregnancy and postpartum are periods of maximum neuronal and behavioral plasticity in a female life. In the present study we investigated whether reproductive experience (number of pregnancies and parturition) affects the behavioral response to an environmental stress as the early mother-pup separation by studying parameters known to be affected by long-term stress.Fil: Aguggia, J. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Suárez, M. M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Rivarola, M. A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Neurociencias (incluye Psicofiosiología

The Italian real-life post-stroke spasticity survey: Unmet needs in the management of spasticity with botulinum toxin type A

The present national survey seeking to identify unmet needs in the management of spasticity with botulinum toxin type A focused on the use of OnabotulinumoxinA, since this is the brand with the widest range of licensed indications in Italy. Physicians from twenty-four Italian neurorehabilitation units compiled a questionnaire about \u201creal-life\u201d post-stroke spasticity management. OnabotulinumtoxinA was reported to be used in the following average doses: upper limb 316.7 \ub1 79.1 units; lower limb 327.8 \ub1 152.3; upper and lower limb 543.7 \ub1 123.7 units. Of the physicians surveyed, 37.5% felt that increasing the frequency of OnabotulinumtoxinA injection would improve its efficacy; 70.8% use electrical stimulation/electromyography guidance (one fourth of injections with no instrumental guidance). Instrumental evaluation was used by 41.7% of the physicians. The participants expressed the view that early identification of post-stroke spasticity would be facilitated by the availability of a post-stroke checklist, and that this should be used by physiotherapists (91.7%), physiatrists (58.3%), family doctors (50%), stroke unit physicians (25%), patients and caregivers (79.2%). According to our findings, the management of poststroke spasticity has several unmet needs that, were they addressed, might improve these patients\u2019 clinical outcomes and quality of life. These needs concern patient follow-up, where a clearly defined pathway is lacking; furthermore, there is a need to use maximum doses per treatment and to ensure early intervention on post-stroke spasticity

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain

Maternal high-fat diet prevents developmental programming by early-life stress

Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.Environnement psychosocial précoce, empreintes biologiques et épigénétiques et état de santé à l'âge adult

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons