Neuroscience
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We have further developed a behavioral model of itch and pain in the lower hindlimb (calf) originally reported by LaMotte et al. (2011) that allows comparisons with responses of lumbar dorsal horn neurons to pruritic and noxious stimuli. Intradermal (id) microinjection of the pruritogens histamine, SLIGRL-NH2 (agonist of PAR-2 and MrgprC11) and chloroquine (agonist of MrgprA3) into the calf of the lower limb elicited significant biting and a small amount of licking directed to the injection site, over a 30-min time course. Following id injection of histamine, low-threshold mechanical stimuli reliably elicited discrete episodes of biting (alloknesis) over a longer time course; significantly less alloknesis was observed following id injection of SLIGRL-NH2. ⋯ This was not observed in histamine-insensitive neurons, or following id injection of saline or SLIGRL-NH2, regardless of whether the latter activated the neuron or not. These results suggest that itch-responsive neurons are selectively sensitized by histamine but not SLIGRL-NH2 to account for alloknesis. The presently described "calf" model appears to distinguish between itch- and pain-related behavioral responses, and provides a basis to investigate lumbar spinal neural mechanisms underlying itch, alloknesis, pain and allodynia.
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Some evidence has shown an increased number of activated microglial cells in patients with schizophrenia. It is hypothesized that activated microglia may contribute to the pathogenesis of schizophrenia. We injected saline or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) into the ventral hippocampus in adult Sprague-Dawley rats via micro-pump; at the same time, the rats were intragastrically administrated with saline or minocycline once a day for 14 consecutive days. ⋯ Minocycline was able to ameliorate deficits of social interaction and PPI but not hyperlocomotion. Minocycline was also able to inhibit the microglial activation. In conclusion, intrahippocampal administration of GM-CSF in adult rats may serve as a potential schizophrenia animal model, which may be related with the microglia hypothesis of schizophrenia.
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Homer is a postsynaptic density (PSD) scaffold protein that is involved in synaptic plasticity, calcium signaling and neurological disorders. Here, we use pre-embedding immunogold electron microscopy to illustrate the differential localization of three Homer gene products (Homer 1, 2, and 3) in different regions of the mouse brain. In cross-sectioned PSDs, Homer occupies a layer ∼30-100nm from the postsynaptic membrane lying just beyond the dense material that defines the PSD core (∼30-nm-thick). ⋯ To determine whether Homer distribution is affected by acute stimulation, we examined its distribution in dissociated hippocampal cultures under different conditions. Both the pattern and density of label for Homer 1, the isoform that is ubiquitous in hippocampus, remained unchanged under high K(+) depolarization (90mM for 2-5min), N-methyl-d-asparic acid (NMDA) treatment (50μM for 2min), and calcium-free conditions (EGTA at 1mM for 2min). In contrast, Shank and calcium/calmodulin-dependent kinase II (CaMKII) accumulate at the PSD upon NMDA treatment, and CaMKII is excluded from the PSD complex under low calcium conditions.
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Spinal cord injury (SCI) is a common and serious trauma which lacks efficient treatment. Inhibition of cell death in the trauma area is important for spinal cord protection during this process. In this study, necroptosis inhibitor necrostatin-1 (Nec-1) was used to treat SCI rats, to investigate the role of Nec-1 in the recovery of SCI. ⋯ Nec-1 as a potential treatment for SCI warrants further study. To our knowledge, this is the first study on the role of Nec-1 in the treatment of traumatic SCI. Our research also found inhibition effects of Nec-1 on apoptosis, not only necroptosis - as reported by most publications.
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Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes cognitive impairment. Major pathophysiological AD characteristics include numerous senile plaque, neurofibrillary tangles, and neuronal loss in the specific regions of patients' brains. In this study, we aimed to understand disease stage-dependent regulation of histone modification for the expression of specific markers in plasma and the hippocampus of in vivo AD model. ⋯ VPA increased the protein levels of NGF in the hippocampus of Tg6799 mice at 5 and 10months of age. In addition, VPA decreased escape latencies of Tg6799 mice at 5 and 10months of age in Morris water maze assessment. Taken together, HDAC inhibition is a promising therapeutic target for AD and it needs to be considered in an age-dependent and/or stage-dependent manner.