Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner.

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks. 2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors. In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.

Genetic parameters and selection of soybean lines based on selection indexes.

Defining selection criteria is important to obtain promising genotypes in a breeding program. The objective of this study was to estimate genetic parameters for agronomic traits and to perform soybean line selection using selection indices. The experiment was conducted at an experimental area located at Capim Branco farm, belonging to the Federal University of Uberlândia. A total of 37 soybean genotypes were evaluated in randomized complete block design with three replicates, in which twelve agronomic traits were evaluated. Analysis of variance, the Scott-Knott test at the 1 and 5% level of probability, and selection index analyses were performed. There was genetic variability for all agronomic traits, with medium to high levels of genotype determination coefficient. Twelve lines with a total cycle up to 110 days were observed and grouped with the cultivars MSOY 6101 and UFUS 7910. Three lines, UFUS FG 03, UFUS FG 20, and UFUS FG 31, were highlighted regarding grain yield with higher values than the national average of 3072 kg/ha. The direct selection enabled the highest trait individual gains. The Williams (1962) index and the Smith (1936) and Hazel (1943) index presented the highest selection gain for the grain yield character. The genotype-ideotype distance index and the index of the sum of ranks of Mulamba and Mock (1978) presented higher values of total selection gain. The lines UFUS FG 12, UFUS FG 14, UFUS FG 18, UFUS FG 25, and UFUS FG 31 were distinguished as superior genotypes by direct selection methods and selection indexes.

Old and new challenges in Parkinson's disease therapeutics.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored.

Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells.

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles-secretome-that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.

Tips on How to Collect and Administer the Mesenchymal Stem Cell Secretome for Central Nervous System Applications.

Human mesenchymal stem cells (hMSCs) have been proposed as possible therapeutic agents for central nervous system (CNS) disorders. Recently, it has been suggested that their effects are mostly mediated through their secretome, which contains a number of neuroregulatory molecules capable of increasing cell proliferation, differentiation, and survival in different physiological conditions. Here, we present an overview of the hMSC secretome as a possible candidate in the creation of new cell-free therapies, demonstrating the process of its collection and route of administration, focusing our attention on their effects in CNS regenerative medicine.

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities.

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

Animal model for chronic massive rotator cuff tear: behavioural and histologic analysis.

PURPOSE: Massive rotator cuff tears (MRCT) are usually chronic lesions that present associated degenerative changes of the myotendinous unit that have been implicated in limitations for surgical repair. In order to develop effective therapies, it is important to establish animal models that mimic the hallmarks of the injury itself. Therefore, in the present work, we aimed to (1) optimize a rodent animal model of MRCT that closely reproduces the fatty infiltration of the cuff muscles seen in humans and (2) describe the effects of unilateral or bilateral lesion in terms of histology and behaviour. METHODS: Massive tear was defined as two rotator cuff tendons-supraspinatus and infraspinatus-section. Twenty-one Wistar rats were randomly assigned to four groups: bilateral lesion (five animals), right-sided unilateral lesion (five animals), left-sided unilateral lesion (five animals) and control (six animals). Behaviour was analyzed with open field and staircase test, 16 weeks after lesion. After that, animals were killed, and the supraspinatus and infraspinatus muscles were processed. RESULTS: Histologic analysis revealed adipocytes, fatty infiltration and atrophy in the injured side with a greater consistency of these degenerative changes in the bilateral lesion group. Behaviour analysis revealed a significant functional impairment of the fine motor control of the forepaw analyzed in staircase test where the number of eaten pellets was significantly higher in sham animals (sham = 7 ± 5.0; left unilateral = 2.6 ± 3.0; right unilateral = 0 ± 0; and bilateral = 0 ± 0, p < 0.05). A trend to reach a lower level of steps, in more injured animals, was also observed (sham animals = 3 ± 1.6 > left unilateral = 2 ± 2.1 > right unilateral = 0.8 ± 1.3 > bilateral = 0.8 ± 1.1). CONCLUSIONS: The present study has been able to establish an animal model that disclosed the hallmarks of MRCT. This can now be used as a valuable, cost-effective, pre-clinical instrument to assist in the development of advanced tissue engineered strategies. Moreover, this animal model overcomes some of the limitations of those that have been reported so far and thus represents a more reliable source for the assessment of future therapeutic strategies with potential clinical relevance.