Neuroscience
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The olfactory bulb (OB) of mammals contains the major endogenous dopamine-producing system in the forebrain. The vast majority of dopaminergic neurons consists of juxtaglomerular cells, which innervate the olfactory glomeruli and modulate the entrance of sensory information to the OB. Although dopaminergic juxtaglomerular cells have been widely investigated, the presence of dopaminergic interneurons other than juxtaglomerular cells has been largely unexplored. ⋯ They receive symmetrical and asymmetrical synapses from GABAergic and non-GABAergic axons of unidentified origin. Our data indicate that the local circuits of the EPL are more complex than previously thought. Although most of the interneurons of this layer establish dendro-dendritic synaptic relationships with principal cells, the TH-containing interneurons constitute an exception to this rule, resembling interneurons from other cortical areas.
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Cancer pain, especially cancer-induced bone pain, affects the quality of life of cancer patients, and current treatments for this pain are limited. The present study demonstrates that spinal extracellular signal-regulated kinase (ERK) activation in glial cells plays a crucial role in cancer-induced bone pain. From day 4 to day 21 after the intra-tibia inoculation with Walker 256 mammary gland carcinoma cells, significant mechanical allodynia was observed as indicated by the decrease of mechanical withdrawal thresholds in the von Frey hair test. ⋯ A single intrathecal injection of the selective MEK (ERK kinase) inhibitors PD98059 (10 μg) on day 12 and U0126 (1.25 and 3 μg) on day 14, attenuated the bilateral mechanical allodynia in the von Frey hair test. Altogether, our results suggest that ERK activation in spinal microglia and astrocytes is correlated with the onset of allodynia and is important for allodynia maintenance in the cancer pain model. This study indicated that inhibition of the ERK pathway may provide a new therapy for cancer-induced bone pain.
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Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. The present study aimed to investigate the effects of high frequency stimulation (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two different stimulation modes i.e. pre-treatment and post-treatment stimulations, mimicking the scheduled and responsive stimulations in clinical use respectively. ⋯ However, Δ(GST-ADT) increased by at least 20 μA in bilateral post-treatment group, while less in bilateral pre-treatment group. Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our data show that anti-epileptic effect of bilateral post-treatment with HFS of ANT is much stronger than that of bilateral pre-treatment HFS, indicating bilateral responsive stimulation might be more appropriate for clinical anti-epileptic treatment of ANT HFS.
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The delayed rectifier voltage-gated potassium channel Kv2.1 underlies a majority of the somatic K(+) current in neurons and is particularly important for regulating intrinsic neuronal excitability. Various stimuli alter Kv2.1 channel gating as well as localization of the channel to cell-surface cluster domains. ⋯ Further, we demonstrate that the C-terminus of Kv2.1 is not necessary for steady-state gating, sensitivity to intracellular phosphatase or NMDA-dependent modulation, though this region is required for localization of Kv2.1 to clusters. Thus, the molecular determinants of Kv2.1 localization and modulation are distinct regions of the channel that function independently.
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Histamine acts centrally to increase energy expenditure and reduce body weight by mechanisms not fully understood. It has been suggested that in the obese state hypothalamic histamine signaling is altered. Previous studies have also shown that histamine acting in the preoptic area controls thermoregulation. ⋯ Similarly, the ability of preoptic histamine signaling to increase the expression of uncoupling proteins was abolished. We also found that the expression of mRNA encoding the H1 receptor subtype in the preoptic area was significantly lower in obese animals. These results indicate that histamine signaling in the preoptic area modulates energy homeostasis by regulating body temperature, metabolic parameters and food intake and that the obese state is associated with a decrease in neurotransmitter's influence.