scholarly journals Role of DSCAM in the Development of Neural Control of Movement and Locomotion

2021 ◽  
Vol 22 (16) ◽  
pp. 8511
Author(s):  
Maxime Lemieux ◽  
Louise Thiry ◽  
Olivier D. Laflamme ◽  
Frédéric Bretzner

Locomotion results in an alternance of flexor and extensor muscles between left and right limbs generated by motoneurons that are controlled by the spinal interneuronal circuit. This spinal locomotor circuit is modulated by sensory afferents, which relay proprioceptive and cutaneous inputs that inform the spatial position of limbs in space and potential contacts with our environment respectively, but also by supraspinal descending commands of the brain that allow us to navigate in complex environments, avoid obstacles, chase prey, or flee predators. Although signaling pathways are important in the establishment and maintenance of motor circuits, the role of DSCAM, a cell adherence molecule associated with Down syndrome, has only recently been investigated in the context of motor control and locomotion in the rodent. DSCAM is known to be involved in lamination and delamination, synaptic targeting, axonal guidance, dendritic and cell tiling, axonal fasciculation and branching, programmed cell death, and synaptogenesis, all of which can impact the establishment of motor circuits during development, but also their maintenance through adulthood. We discuss herein how DSCAM is important for proper motor coordination, especially for breathing and locomotion.

1997 ◽  
Vol 273 (2) ◽  
pp. G447-G455 ◽  
Author(s):  
T. Shea-Donohue ◽  
J. M. Goldhill ◽  
E. Montcalm-Mazzilli ◽  
C. Colleton ◽  
V. M. Pineiro-Carrero ◽  
...  

The role of sensory afferents in inflammation-induced alterations in myoelectric activity in vivo was investigated in the rabbit small intestine. Isolated ileal loops were implanted with serosal electrodes and exposed to ricin or vehicle after pretreatment with 125 mg/kg of subcutaneous (125 mg over 3 days) or intraluminal (640 microM) capsaicin. After 5 h of myoelectric recording, the loops were prepared for histology and for ex vivo generation of eicosanoids. Capsaicin exacerbated mucosal damage after exposure to ricin but did not alter neutrophil infiltration. Subcutaneous capsaicin alone elevated slow-wave frequency and spike events and transiently suppressed the myoelectric response to ricin. In contrast, intraluminal capsaicin alone did not alter myoelectric activity but produced a sustained inhibition of the response to ricin. Eicosanoid production was unchanged by capsaicin alone. Intraluminal capsaicin blocked increases in leukotriene C4 and prostaglandin E2 during inflammation, an effect that paralleled its inhibition of myoelectric activity. Thus the contribution of sensory afferents to altered motility during acute ileitis involves the release of mucosal inflammatory mediators that influence neural control of smooth muscle.


2015 ◽  
Vol 24 (01) ◽  
pp. 7-10 ◽  
Author(s):  
M. Pfeifer ◽  
M. Sinaki

SummaryThe objective of exercise in the treatment of osteoporosis is to improve axial stability through strengthening of back extensor muscles. Therefore, a back extension exercise program specific to one’s musculoskeletal competence and pain can be performed in a sitting position and later advanced to the prone position. When fragility is resolved, back extension is performed against resistance applied to the upper back. A significant reduction in back pain, kyphosis, and risk of falls and an improvement in the level of physical activity have been achieved through the SPEED (Spinal Proprioceptive Extension Exercise Dynamic) program. In addition, the application of a “Posture Training Support” (PTS) using a backpack may decrease kyphosis and pain related not only to compression fractures but also reduce iliocostal friction. Therapeutic exercise should address osteo - porosis-related deformities of axial posture, which can increase risk of fall and fracture. Thus, the role of a therapeutic exercise program is to increase muscle strength safely, decrease immobility-related complications, and prevent fall and fracture. As with pharmacotherapy, therapeutic exercises are individualized.


2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.


2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.


2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0015
Author(s):  
Cody R. Criss ◽  
Dustin R. Grooms ◽  
Jed A. Diekfuss ◽  
Manish Anand ◽  
Alexis B. Slutsky-Ganesh ◽  
...  

Background: Anterior cruciate ligament (ACL) injuries predominantly occur via non-contact mechanisms, secondary to motor coordination errors resulting in aberrant frontal plane knee loads that exceed the thresholds of ligament integrity. However, central nervous system processing underlying high injury-risk motor coordination errors remain unknown, limiting the optimization of current injury reduction strategies. Purpose: To evaluate the relationships between brain activity during motor tasks with injury-risk loading during a drop vertical jump. Methods: Thirty female high school soccer players (16.10 ± 0.87 years, 165.10 ± 4.64 cm, 63.43 ± 8.80 kg) were evaluated with 3D biomechanics during a standardized drop vertical jump from a 30 cm box and peak knee abduction moment was extracted as the injury-risk variable of interest. A neuroimaging session to capture neural activity (via blood-oxygen-level-dependent signal) was then completed which consisted of 4 blocks of 30 seconds of repeated bilateral leg press action paced to a metronome beat of 1.2 Hz with 30 seconds rest between blocks. Knee abduction moment was evaluated relative to neural activity to identify potential neural contributors to injury-risk. Results: There was a direct relationship between increased landing knee abduction moment and increased neural activation within regions corresponding to the lingual gyrus, intracalcarine cortex, posterior cingulate cortex, and precuneus (r2= 0.68, p corrected < .05, z max > 3.1; Table 1 & Figure 1). Conclusion: Elevated activity in regions that integrate sensory, spatial, and attentional information may contribute to elevated frontal plane knee loads during landing. Interestingly, a similar activation pattern related to high-risk landing mechanics has been found in those following injury, indicating that predisposing factors to injury may be accentuated by injury or that modern rehabilitation does not recover prospective neural control deficits. These data uncover a potentially novel brain marker that could guide the discovery of neural-therapeutic targets that reduce injury risk beyond current prevention methods. [Table: see text][Figure: see text]


1998 ◽  
Vol 143 (4) ◽  
pp. 921-933 ◽  
Author(s):  
Susana Silberstein ◽  
Gabriel Schlenstedt ◽  
Pam A. Silver ◽  
Reid Gilmore

Members of the eukaryotic heat shock protein 70 family (Hsp70s) are regulated by protein cofactors that contain domains homologous to bacterial DnaJ. Of the three DnaJ homologues in the yeast rough endoplasmic reticulum (RER; Scj1p, Sec63p, and Jem1p), Scj1p is most closely related to DnaJ, hence it is a probable cofactor for Kar2p, the major Hsp70 in the yeast RER. However, the physiological role of Scj1p has remained obscure due to the lack of an obvious defect in Kar2p-mediated pathways in scj1 null mutants. Here, we show that the Δscj1 mutant is hypersensitive to tunicamycin or mutations that reduce N-linked glycosylation of proteins. Although maturation of glycosylated carboxypeptidase Y occurs with wild-type kinetics in Δscj1 cells, the transport rate for an unglycosylated mutant carboxypeptidase Y (CPY) is markedly reduced. Loss of Scj1p induces the unfolded protein response pathway, and results in a cell wall defect when combined with an oligosaccharyltransferase mutation. The combined loss of both Scj1p and Jem1p exaggerates the sensitivity to hypoglycosylation stress, leads to further induction of the unfolded protein response pathway, and drastically delays maturation of an unglycosylated reporter protein in the RER. We propose that the major role for Scj1p is to cooperate with Kar2p to mediate maturation of proteins in the RER lumen.


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