Neuroscience
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Noise-induced hearing loss generally induces loudness recruitment, but sometimes gives rise to hyperacusis, a debilitating condition in which moderate intensity sounds are perceived abnormally loud. In an attempt to develop an animal model of loudness hyperacusis, we exposed rats to a 16-20 kHz noise at 104 dB SPL for 12 weeks. Behavioral reaction time-intensity functions were used to assess loudness growth functions before, during and 2-months post-exposure. ⋯ Consistent with central gain models, the gross neural responses from the auditory cortex and amygdala were proportionately much larger than those from the cochlea. However, despite central amplification, the population responses in the auditory cortex and amygdala were still below the level needed to fully account for hyperacusis and/or recruitment. Having developed procedures that can consistently induce hyperacusis in rats, our results set the stage for future studies that seek to identify the neurobiological events that give rise to hyperacusis and to develop new therapies to treat this debilitating condition.
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This study compared the effects of fatigue on corticospinal responsiveness in the upper- and lower-limb muscles of the same participants. Seven healthy males performed a 2-min maximal voluntary isometric contraction of the elbow flexors or knee extensors on four separate days. Electromyographic responses were elicited by nerve stimulation (maximal M-wave) in all sessions and by transcranial magnetic stimulation (motor-evoked potential; silent period) and spinal tract stimulation (cervicomedullary or thoracic motor-evoked potentials; silent period) in one session each per limb. ⋯ Sustained maximal contractions elicit different neurophysiological adjustments in upper- and lower-limb muscles. Specifically, motoneuronal excitability was reduced in biceps brachii, but not in rectus femoris, and this reduction required greater compensatory adjustments from the motor cortex. Therefore, changes in cortical and spinal excitability during sustained maximal exercise are likely specific to the muscle performing the task.
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We explore whether near infrared light can change patterns of resting (task-negative) and/or evoked (task-positive; eg finger-tapping) brain activity in normal, young human subjects using fMRI (functional magnetic resonance imaging). To this end, we used a vielight transcranial device (810 nm) and compared the scans in subjects after active- and sham-light sessions. Our fMRI results showed that, while light had no effect on cerebral blood flow and global resting state brain activity (task-negative), there were clear differences between the active- and sham-light sessions in the patterns of evoked brain activity after finger-tapping (task-positive). ⋯ In summary, our fMRI findings indicated that transcranially applied light did have a major impact on brain activity in normal subjects, but only when the brain region was itself functionally active, when undertaking a particular task. We suggest that these light-induced changes, particularly those in parietal association cortex, were associated with attention and novelty, and served to deactivate the so-called default mode network. Our results lay the template for our planned fMRI explorations into the effects of light in both Alzheimer's and Parkinson's disease patients.
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Accumulation of microtubule associated protein tau in the substantia nigra is associated with several tauopathies including progressive supranuclear palsy (PSP). A number of studies have used mutant tau transgenic mouse model to mimic the neuropathology of tauopathies and disease phenotypes. However, tau expression in these transgenic mouse models is not specific to brain subregions, and may not recapitulate subcortical disease phenotypes of PSP. ⋯ Furthermore, the iAAV-tau-injected mice displayed severe motor deficits including impaired movement ability, motor balance, and motor coordination compared to the control groups over a short time-course. Immunochemical analysis revealed that tau gene transfer significantly resulted in loss of tyrosine hydroxylase-positive dopaminergic neurons and elevated phosphorylated tau in the substantia nigra. Our development of dopaminergic neuron-specific neurodegenerative mouse model with tauopathy will be helpful for studying the underlying mechanism of pathological protein propagation as well as development of new therapies.
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Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. ⋯ The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.