Neuroscience
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It is unclear how haptic touch with a stable surface reduces postural sway. We hypothesized that haptic input enhances postural stability due to alterations in axial postural tone. We measured the influence of heavy and light touch (LT) of the hands on a stable bar on axial postural tone and postural sway during stance in 14 healthy adults. ⋯ This is the first study showing that axial postural tone can be modified by remote somatosensory input and provides a potential explanation for how light touch improves postural stability. Changes in subjects' perception from trunk to surface rotation when changing from no touch (NT) to haptic touch, suggests that the CNS changes from using a global, to a local, trunk reference frame for control of posture during touch. The increase of hip postural tone during touching and gripping can be explained as a suppression of hip muscle shortening reactions that normally assist axial rotation.
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Clinical and experimental evidence demonstrates that endocannabinoids play either beneficial or adverse roles in many neurological and psychiatric disorders. Their medical significance may be best explained by the emerging concept that endocannabinoids are essential modulators of synaptic transmission throughout the central nervous system. However, the precise molecular architecture of the endocannabinoid signaling machinery in the human brain remains elusive. ⋯ However, as observed previously in rodent hippocampus, MGL was enriched in axon terminals instead of postsynaptic structures at the ultrastructural level. Taken together, these findings demonstrate the post- and presynaptic segregation of primary enzymes responsible for synthesis and elimination of 2-AG, respectively, in the human hippocampus. Thus, molecular architecture of the endocannabinoid signaling machinery supports retrograde regulation of synaptic activity, and its similar blueprint in rodents and humans further indicates that 2-AG's physiological role as a negative feed-back signal is an evolutionarily conserved feature of excitatory synapses.
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Current evidence suggests that exercise and glial cell line-derived neurotrophic factor (GDNF) independently cause significant morphological changes in the neuromuscular system. The aim of the current study was to determine if increased physical activity regulates GDNF protein content in rat skeletal muscle. Extensor Digitorum Longus (EDL) and Soleus (SOL) hind limb skeletal muscles were analyzed following 2 weeks of involuntary exercise and 4 h of field stimulation or stretch in muscle bath preparations. ⋯ Pre-treatment with α-bungarotoxin abolished the effects of field stimulation in both muscles and blocked the effect of stretch in EDL. α-bungarotoxin pre-treatment and stretch increased GDNF protein content to 240%±10% of controls in the SOL. Exposure to carbamylcholine decreased GDNF protein content to 51%±28% of controls in the EDL but not SOL. These results suggest that GDNF protein content in skeletal muscle may be controlled by stretch, where it may increase GDNF protein content, and membrane depolarization/acetylcholine (ACh) which acts to decrease GDNF protein content.
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Paclitaxel is one of the most commonly used anti-neoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. ⋯ Intraperitoneal administration of l-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived l-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.
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A mouse model of amyloid pathology was used to first examine using a cross sectional design changes in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: (1) overt amyloid labeled with β-amyloid((1-42)) and Congo Red staining, (2) metabolic function assessed by the enzyme, cytochrome oxidase, and (3) neuronal activity as assessed indirectly by the immediate-early gene (IEG), c-Fos. ⋯ Subsequent analyses concentrating on this early dysfunction revealed at 5 months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction.