Scientific reports
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As mammals age, their neuromuscular junctions (NMJs) gradually change their form, acquiring an increasingly fragmented appearance consisting of numerous isolated regions of synaptic differentiation. It has been suggested that this remodelling is associated with impairment of neuromuscular transmission, and that this contributes to age-related muscle weakness in mammals, including humans. ⋯ Here, by comparing the structure and function of individual NMJs, we show that neuromuscular transmission at the most highly fragmented NMJs in the diaphragms of old (26-28 months) mice is, if anything, stronger than in middle-aged (12-14 months) mice. We suggest that NMJ fragmentation per se is not a reliable indicator of impaired neuromuscular transmission.
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The relationship between M1 activity representing motor information in real and imagined movements have not been investigated with high spatiotemporal resolution using non-invasive measurements. We examined the similarities and differences in M1 activity during real and imagined movements. Ten subjects performed or imagined three types of right upper limb movements. ⋯ Single virtual channel-based analysis showed that decoding accuracy significantly increased around the hand and arm areas during real and imagined movements and that these are spatially correlated. The temporal correlation of decoding accuracy significantly increased around the hand and arm areas, except for the period immediately after response onset. Our results suggest that cM1 is involved in similar neural activities related to the representation of motor information during real and imagined movements, except for presence or absence of sensory-motor integration induced by sensory feedback.
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Drug-resistant, multifocal, non-resectable epilepsies are among the most difficult epileptic disorders to manage. An approach to control previously uncontrollable seizures in epilepsy patients would consist of identifying seizure precursors in critical brain areas combined with delivering a counteracting influence to prevent seizure generation. Predictability of seizures with acceptable levels of sensitivity and specificity, even in an ambulatory setting, has been repeatedly shown, however, in patients with a single seizure focus only. ⋯ Unexpectedly, the emergence of seizure precursors was confined to non-affected brain areas. Our findings clearly indicate that epileptic networks, spanning lobes and hemispheres, underlie generation of seizures. Our proof-of-concept study is an important milestone towards new therapeutic strategies based on seizure-prediction techniques for clinical practice.
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E-52862 is a selective σ1R antagonist currently undergoing phase II clinical trials for neuropathic pain and represents a potential first-in-class analgesic. Here, we investigated the effect of single and repeated administration of E-52862 on different pain-related behaviours in several neuropathic pain models in rats: mechanical allodynia in cephalic (trigeminal) neuropathic pain following chronic constriction injury of the infraorbital nerve (IoN), mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic polyneuropathy, and cold allodynia in oxaliplatin (OX)-induced polyneuropathy. Mechanical hypersensitivity induced after IoN surgery or STZ administration was reduced by acute treatment with E-52862 and morphine, but not by pregabalin. ⋯ Interestingly, repeated E-52862 administration twice daily over 7 days did not induce pharmacodynamic tolerance but an increased antinociceptive effect in all three models. Additionally, as shown in the STZ and OX models, repeated daily treatment with E-52862 attenuated baseline pain behaviours, which supports a sustained modifying effect on underlying pain-generating mechanisms. These preclinical findings support a role for σ1R in neuropathic pain and extend the potential for the use of selective σ1R antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain.
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The domestic dog is one of our most popular companions and longest relationships, occupying different roles, from pet to working guide dog for the blind. As dogs age different behavioural issues occur and in some cases dogs may be relinquished or removed from their working service. Here we analyse a dataset on working guide dogs that were removed from their service between 1994 and 2013. ⋯ The age at withdrawal for the different withdrawal reasons suggested that dogs were more likely to develop fear/aggression related issues early on, whilst issues related to training could develop at almost any age. We found no evidence for heterosis effecting behaviour. We believe that this work is relevant to the pet dog population and had implications for understanding ageing and genetic influences on behaviour.