| 1. |
- Blomgren, Klas, 1963, et al.
(författare)
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Pathological apoptosis in the developing brain
- 2007
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Ingår i: Apoptosis. - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 12:5, s. 993-1010
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Forskningsöversikt (refereegranskat)abstract
- More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further development of remaining cells, is called programmed cell death (PCD). The term apoptosis is used to describe certain morphological manifestations of PCD. Many of the effectors of this developmental cell death program are highly expressed in the developing brain, making it more susceptible to accidental activation of the death machinery, e.g. following hypoxia-ischemia or irradiation. Recent evidence suggests, however, that activation and regulation of cell death mechanisms under pathological conditions do not exactly mirror physiological, developmentally regulated PCD. It may be argued that the conditions after e.g. ischemia are not even compatible with the execution of PCD as we know it. Under pathological conditions cells are exposed to various stressors, including energy failure, oxidative stress and unbalanced ion fluxes. This results in parallel triggering and potential overshooting of several different cell death pathways, which then interact with one another and result in complex patterns of biochemical manifestations and cellular morphological features. These types of cell death are here called "pathological apoptosis," where classical hallmarks of PCD, like pyknosis, nuclear condensation and caspase-3 activation, are combined with non-PCD features of cell death. Here we review our current knowledge of the mechanisms involved, with special focus on the potential for therapeutic intervention tailored to the needs of the developing brain.
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| 2. |
- Adiels, Martin, 1976, et al.
(författare)
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Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans.
- 2015
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 6:NOV, s. 342-
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Forskningsöversikt (refereegranskat)abstract
- To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.
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| 3. |
- Backman, Lars, et al.
(författare)
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Dopamine and training-related working-memory improvement
- 2013
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier. - 0149-7634 .- 1873-7528. ; 37:9, s. 2209-2219
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Forskningsöversikt (refereegranskat)abstract
- Converging evidence indicates that the neurotransmitter dopamine (DA) is implicated in working-memory (WM) functioning and that WM is trainable. We review recent work suggesting that DA is critically involved in the ability to benefit from WM interventions. Functional MRI studies reveal increased striatal BOLD activity following certain forms of WM interventions, such as updating training. Increased striatal BOLD activity has also been linked to transfer of learning to non-trained WM tasks, suggesting a neural signature of transfer. The striatal BOLD signal is partly determined by DA activity. Consistent with this assertion, PET research demonstrates increased striatal DA release during updating of information in WM after training. Genetic studies indicate larger increases in WM performance post training for those who carry advantageous alleles of DA-relevant genes. These patterns of results corroborate the role of DA in WM improvement. Future research avenues include: (a) neuromodulatory correlates of transfer; (b) the potential of WM training to enhance DA release in older adults; (c) comparisons among different WM processes (i.e., updating, switching, inhibition) regarding regional patterns of training-related DA release; and (d) gene-gene interactions in relation to training-related WM gains.
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| 4. |
- McGlone, Francis, et al.
(författare)
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Discriminative and Affective Touch: Sensing and Feeling.
- 2014
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 82:4, s. 737-755
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Forskningsöversikt (refereegranskat)abstract
- The multimodal properties of the human somatosensory system continue to be unravelled. There is mounting evidence that one of these submodalities-touch-has another dimension, providing not only its well-recognized discriminative input to the brain, but also an affective input. It has long been recognized that touch plays an important role in many forms of social communication and a number of theories have been proposed to explain observations and beliefs about the "power of touch." Here, we propose that a class of low-threshold mechanosensitive C fibers that innervate the hairy skin represent the neurobiological substrate for the affective and rewarding properties of touch.
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| 5. |
- Menzies, John R W, et al.
(författare)
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Ghrelin, reward and motivation.
- 2013
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Ingår i: Endocrine development. - : S. Karger AG. - 1662-2979. ; 25, s. 101-11
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Forskningsöversikt (refereegranskat)abstract
- Almost all circulating gut peptides contribute to the control of food intake by signalling satiety. One important exception is ghrelin, the only orexigenic peptide hormone thus far described. Ghrelin secretion increases before meals and behavioural and electrophysiological evidence shows that ghrelin acts in the hypothalamus via homeostatic pathways to signal hunger and increase food intake and adiposity. These findings strongly suggest that ghrelin is a dynamically regulated peripheral hunger signal. However, ghrelin also interacts with the brain reward pathways to increase food intake, alter food preference and enhance food reward. Here we discuss ghrelin's role as an endocrine gut-brain reward signal in relation to homeostatic and hedonic feeding control.
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| 6. |
- Rostedt Punga, Anna, et al.
(författare)
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Keeping up appearances : Don't frown upon the effects of botulinum toxin injections in facial muscles
- 2023
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Ingår i: Clinical Neurophysiology Practice. - : Elsevier. - 2467-981X. ; 8, s. 169-173
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Forskningsöversikt (refereegranskat)abstract
- Aesthetic use of low doses of Botulinum toxin (BoNT) injections into the facial muscles has become a leading non-surgical aesthetic treatment worldwide to reduce facial wrinkles, including glabellar lines, forehead lines, and periorbital wrinkles. Within these aesthetic applications, BoNT injections intend to reduce and prevent wrinkles, and the recommended usage of 2 years is often exceeded, which may result in atrophy of the injected muscles. The long-term effects of BoNT injections in the facial muscles and the evidence of diffusion of BoNT to surrounding muscles are obvious pitfalls and challenges for clinical neurophysiologists in differential diagnosing neuromuscular transmission failures. Also, this is further complicated by the risk of developing side effects upon permanent chemical denervation of facial muscles, with less possibility for reinnervation.This review summarizes the known long-term effects of BoNT over time in different facial muscles and the use of objective electrophysiological measures to evaluate these. A better understanding of the longterm effects of BoNT is essential to avoid misdiagnosing other neuromuscular disorders.
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| 7. |
- Uvnäs-Moberg, Kerstin, et al.
(författare)
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Neuroendocrine mechanisms involved in the physiological effects caused by skin-to-skin contact - With a particular focus on the oxytocinergic system
- 2020
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Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 61:November
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Forskningsöversikt (refereegranskat)abstract
- The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system.The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed.The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective.The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby’s crawling behavior) are expressions of oxytocin’s ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin’s ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin’s ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth.The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors.It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.
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| 8. |
- Belizário, José E., et al.
(författare)
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Skeletal muscle wasting and renewal : a pivotal role of myokine IL-6
- 2016
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5:1
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Forskningsöversikt (refereegranskat)abstract
- Adult skeletal tissue is composed of heterogeneous population of cells that constantly self-renew by means of a controlled process of activation and proliferation of tissue-resident stem cells named satellite cells. Many growth factors, cytokines and myokines produced by skeletal muscle cells play critical roles in local regulation of the inflammatory process and skeletal muscle regeneration during different pathological conditions. IL-6 is a pleiotropic cytokine released in large amount during infection, autoimmunity and cancer. Low levels of IL-6 can promote activation of satellite cells and myotube regeneration while chronically elevated production promote skeletal muscle wasting. These distinct effects may be explained by a crosstalk of the IL-6/IL-6 receptor and gp130 trans-signaling pathway that oppose to regenerative and anti-inflammatory of the classical IL-6 receptor signaling pathway. Here we discuss on potential therapeutic strategies using monoclonal antibodies to IL-6R for the treatment of skeletal muscle wasting and cachexia. We also highlight on the IL-6/JAK/STAT and FGF/p38αβ MAPK signaling pathways in satellite cell activation and the use of protein kinase inhibitors for tailoring and optimizing satellite cell proliferation during the skeletal muscle renewal. Future investigations on the roles of the IL-6 classical and trans-signaling pathways in both immune and non-immune cells in skeletal muscle tissue will provide new basis for therapeutic approaches to reverse atrophy and degeneration of skeletal muscles in cancer and inflammatory diseases.
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| 9. |
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| 10. |
- Hammarstedt, Ann, 1975, et al.
(författare)
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Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity
- 2018
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Ingår i: Physiological Reviews. - : American Physiological Society. - 0031-9333 .- 1522-1210. ; 98:4, s. 1911-1941
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Forskningsöversikt (refereegranskat)abstract
- The subcutaneous adipose tissue (SAT) is the largest and best storage site for excess lipids. However, it has a limited ability to expand by recruiting and/or differentiating available precursor cells. When inadequate, this leads to a hypertrophic expansion of the cells with increased inflammation, insulin resistance, and a dysfunctional prolipolytic tissue. Epi-/genetic factors regulate SAT adipogenesis and genetic predisposition for type 2 diabetes is associated with markers of an impaired SAT adipogenesis and development of hypertrophic obesity also in nonobese individuals. We here review mechanisms for the adipose precursor cells to enter adipogenesis, emphasizing the role of bone morphogenetic protein-4 (BMP-4) and its endogenous antagonist gremlin-1, which is increased in hypertrophic SAT in humans. Gremlin-1 is a secreted and a likely important mechanism for the impaired SAT adipogenesis in hypertrophic obesity. Transiently increasing BMP-4 enhances adipogenic commitment of the precursor cells while maintained BMP-4 signaling during differentiation induces a beige/brown oxidative phenotype in both human and murine adipose cells. Adipose tissue growth and development also requires increased angiogenesis, and BMP-4, as a proangiogenic molecule, may also be an important feedback regulator of this. Hypertrophic obesity is also associated with increased lipolysis. Reduced lipid storage and increased release of FFA by hypertrophic SAT are important mechanisms for the accumulation of ectopic fat in the liver and other places promoting insulin resistance. Taken together, the limited expansion and storage capacity of SAT is a major driver of the obesity-associated metabolic complications.
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