Neuroscience
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The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. ⋯ Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning <20 mm along the superior-inferior axis. In a subset of participants (n = 10), the cervical spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity.
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Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking. ⋯ The mRNA signal in the SVZ and the hippocampus was substantially increased by the LPS treatment without detectable changes elsewhere. These results demonstrate that KAT II is expressed in the rat brain in a region-specific manner and that gene expression is sensitive to inflammatory processes. This suggests an unrecognized role for kynurenic acid in the brain's germinal zones.
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Zinc-containing terminals are found throughout the neocortex, concentrated predominantly in layers II/III, V, and VI. Synaptic zinc is a potent neurotransmitter/modulator and, therefore, may mediate inter- or intra-cortical integration of sensory information. We have previously shown that levels of synaptic zinc are rapidly modulated in somatosensory (barrel) cortex, in an experience- and activity-dependent manner. ⋯ ZnT3 KO mice were not able to discriminate between textures having an average particle diameter less than 300 μm while control mice were able to discriminate between textures having particle diameters separated by as little as 25 μm. This loss of texture discrimination acuity in ZnT3 KO mice was whisker-dependent and was observed in young (2 months-of-age) and older mice (12 months-of-age). These results show that zincergic signaling is necessary for the normal integration of somatosensory information.
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Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. ⋯ Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development.
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Malaria, parasitic disease considered a major health public problem, is caused by Plasmodium protozoan genus and transmitted by the bite of infected female Anopheles mosquito genus. Cerebral malaria (CM) is the most severe presentation of malaria, caused by P. falciparum and responsible for high mortality and enduring development of cognitive deficits which may persist even after cure and cessation of therapy. In the present study we evaluated selected behavioral, neurochemical and neuropathologic parameters after rescue from experimental cerebral malaria caused by P. berghei ANKA in C57BL/6 mice. ⋯ Interestingly, no changes in the neuropathological markers Fluoro-Jade C, Timm staining or IBA-1 were detected. Altogether, present data indicate that behavioral and neurochemical alterations persist even after parasitemia clearance and CM recovery, which agrees with available clinical findings. Some of the molecular mechanisms reported in the present study may underlie the behavioral changes and increased seizure susceptibility that persist after recovery from CM and may help in the future development of therapeutic strategies for CM sequelae.