Neuroscience
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GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1). ⋯ As loss of MAG has previously been shown to result in increased susceptibility to brain insults, we additionally assessed Gpr37-knockout (Gpr37-/-) vs. wild-type mice in the cuprizone model of demyelination. These studies revealed that Gpr37-/- mice exhibit dramatically increased loss of myelin in response to cuprizone, yet do not show any increased loss of oligodendrocyte precursor cells or mature oligodendrocytes. These findings reveal that loss of GPR37 alters oligodendrocyte physiology and increases susceptibility to demyelination, indicating that GPR37 could be a potential drug target for the treatment of demyelinating diseases such as multiple sclerosis.
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The current decerebration procedures discard the role of the thalamus in the motor control and decortication only rules out the brain cortex part, leaving a gap between the brain cortex and the subthalamic motor regions. In here we define a new preparation denominated Brain Cortex-Ablated Cat (BCAC), in which the frontal and parietal brain cortices as well as the central white matter beneath them were removed, this decerebration process may be considered as suprathalamic, since the thalamus remained intact. To characterize this preparation cat hindlimb electromyograms (EMG), kinematics and cutaneous reflexes (CR) produced by electrical stimulation of sural (SU) or saphenous (SAPH) nerves were analyzed during locomotion in intact and in BCAC. ⋯ In intact cats CR produced an inhibition of extensors, as well as excitation and inhibition of flexors, and a complex pattern of withdrawal responses in bifunctional muscles. The same stimuli applied to BCAC produced no detectable responses, but in some cats cutaneous reflexes produced by electrical stimulation of saphenous nerve reappeared when the locomotion speed increased. In BCAC, EMG and kinematic changes, as well as the absence of CR, imply that for this cat preparation there is a partial compensation due to the subcortical locomotor apparatus generating close to normal locomotion.
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Previous studies have shown that aging modifies taste sensitivity. However, the factors affecting the changes in taste sensitivity remain unclear. To investigate the cause of the age-related changes in taste sensitivity, we compared the peripheral taste detection systems in young and old mice. ⋯ Based on these findings, we conclude that changes in taste sensitivity with aging were not caused by aging-related degradation of peripheral taste organs. Meanwhile, the concentrations of several serum components that modify taste responses changed with age. Thus, taste signal-modifying factors such as serum components may have a contributing role in aging-related changes in taste sensitivity.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory. The neurodegeneration induced by AD has been linked to oxidative damage. However, little is known about the involvement of NADPH oxidase 2 (Nox2), a multisubunit enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the pathogenesis of AD. ⋯ STZ treatment increased oxidative damage and pro-inflammatory cytokines' release in Wt mice, which was not observed in gp91phox-/- mice. Nox2 deletion had a positive effect on the IL-10 baseline production, suggesting that this cytokine might contribute to the neuroprotection mechanism against STZ-induced neurodegeneration. In summary, our data suggest that the Nox2-dependent reactive oxygen species (ROS) generation contributes to the STZ-induced AD-like state.
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Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. ⋯ Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg9-bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain.