Neuroscience
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Parkinson's disease (PD) is known to affect postural control, especially in situations needing a change in balance strategy or when a concurrent task is simultaneously performed. However, few studies assessing postural control in patients with PD included homogeneous population in late stage of the disease. Thus, this study aimed to analyse postural control and strategies in a homogeneous population of patients with idiopathic advanced (late-stage) PD, and to determine the contribution of peripheral inputs in simple and more complex postural tasks, such as sensory conflicting and dynamic tasks. ⋯ In DPT, postural restabilization strategies were often inefficient to maintain equilibrium resulting in falls. Postural strategies were often precarious, postural regulation involving more hip joint than ankle joint in patients with advanced PD than in controls. Difficulties in managing complex postural situations, such as sensory conflicting and dynamic situations might reflect an inadequate sensory organization suggesting impairment in central information processing.
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Efficient encoding of sensory information can be implemented by heterogeneous response properties of neurons within sensory pathways. In the auditory system, neurons in the main auditory midbrain nucleus, the inferior colliculus (IC), show heterogeneous response properties to various types of acoustic stimuli including behaviorally relevant sounds. The receptive fields of these neurons, and their spatial organization, may reveal mechanisms that underlie response heterogeneity in the IC. ⋯ We found that the tonotopic progression is discontinuous in mouse IC, and we found that there is no clear spatial organization of frequency tuning curve types. Rather, there is heterogeneity of receptive fields in the bulk of the IC such that frequency tuning characteristics and hence the structure of excitatory and inhibitory inputs does not depend on location in the IC. This heterogeneity likely provides a mechanism for efficient encoding of auditory stimuli throughout the extent of the mouse IC.
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Peripheral neuropathy is a common and major complication of diabetes, the underlying mechanisms of which are not fully understood. Using a mouse model of type II diabetes, the present study investigated the role of phosphodiesterase-5 (PDE5) in peripheral neuropathy. BKS. ⋯ Blockage of PDE5 with sildenafil increased cyclic guanosine monophosphate (cGMP) and completely abolished the effect of hyperglycemia on Schwann cells. Sildenafil upregulated cGMP-dependent protein kinase G I (PKGI), whereas inhibition of PKGI with a PKG inhibitor, KT5823, suppressed the inhibitory effect of sildenafil on Schwann cells. These data indicate that hyperglycemia substantially upregulates PDE5 expression and that the cGMP/PKG signaling pathway activated by sildenafil mediates the beneficial effects of sildenafil on diabetic peripheral neuropathy.
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Manual acupuncture (MA) has presented analgesic activity against neuropathic pain in patients and animal models, yet a series of questions remain: Is MA effectiveness dependent of acupoint selection or combination? Is it equally efficient when treatment starts on the initial (acute) or sub-chronic phase of spinal nerve ligation (SNL)-induced neuropathy? Is MA effect related to the release of endogenous opioids? Does MA produce similar effects to gabapentin? To answer these questions rats submitted to the L5/L6 SNL injury were treated with unilateral MA (ST36 (Zusanli), SP6 (Sanyingjiao) or ST36+SP6 acupoint stimulation); or with gabapentin (30 mg/kg i.p., used as positive control). Both acupoints have been demonstrated to present analgesic activity and are used in clinical practice and basic science research. ⋯ Our results demonstrate that single or combined unilateral stimulation was able to reduce mechanical hypersensitivity with treatment beginning in both acute and sub-chronic phases of SNL-induced neuropathy; MA effect was blocked by naloxone, and finally; SP6+ST36 MA presented similar effect to gabapentin (30 mg/kg). In conclusion, our results demonstrate, for the first time, that unilateral MA (ST36, SP6 or ST36+SP6) reduces hypersensitivity induced by the SNL with effect dependent of the opioid system and comparable with the one obtained with gabapentin (used as positive control).
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Amyloid beta (Aβ) has been proposed to play a central and causative role in the development of Alzheimer's disease. Aβ(25-35), the neurotoxic domain of the full-length Aβ, causes learning and memory impairments in rodents. The present study investigated the effects of a single bilateral i.c.v. infusion of pre-aggregated Aβ(25-35) (30 nmol/rat) on animals' performance in the open field, and on arginine metabolic enzymes and metabolites in the CA1, CA2/3, and dentate gyrus (DG) sub-regions of the hippocampus and prefrontal cortex (PFC) at the time point of 6-8 days after Aβ infusion. ⋯ Cluster analyses were performed to determine if the nine related neurochemical variables (arginine, citrulline, ornithine, agmatine, putrescine, spermidine, spemine, glutamate, and GABA) formed distinct groups, and whether it changed as a function of Aβ(25-35). There were substantially different clusters between the two groups in the hippocampus and PFC. These results demonstrate that Aβ(25-35) alters arginine metabolism, which further supports the prominent role of arginine and its metabolites in Alzheimer's disease (AD) pathogenesis.