Neuroscience
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We have previously found that tissue type and urokinase type plasminogen activators (tPA and uPA) are induced in dorsal root ganglia (DRG) neurons after peripheral axotomy and that tPA plays crucial roles in generating neuropathic pain. Here we examined whether the plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) mRNA, endogenous inhibitors of tPA and uPA, are induced in the DRG following sciatic nerve transection. L4 and L5 DRG sections were examined using in situ hybridization histochemistry. ⋯ The precise expression patterns of PAI-1 and PAI-2 mRNA at 3 days after axotomy revealed that PAI-1 mRNA was observed in predominantly small neurons, while much of the PAI-2 mRNA was expressed in large neurons. Double-labeling analysis of these mRNAs with activated transcription factor 3, known as an injury marker, revealed that most PAI-1 and PAI-2 mRNAs was induced in injured neurons. Co-expression of PAI-1, 2 with tPA and uPA in DRG neurons suggests that these inhibitors may act in an autocrine manner to modulate extracellular proteolytic activity after nerve injury.
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Endocannabinoid signaling, mediated by presynaptic CB1 cannabinoid receptors on neurons, is fundamental for the maintenance of synaptic plasticity by modulating neurotransmitter release from axon terminals. In the rodent basal forebrain, CB1 cannabinoid receptor-like immunoreactivity is only harbored by a subpopulation of cholinergic projection neurons. However, endocannabinoid control of cholinergic output from the substantia innominata, coincident target innervation of cholinergic and CB1 cannabinoid receptor-containing afferents, and cholinergic regulation of endocannabinoid synthesis in the hippocampus suggest a significant cholinergic-endocannabinergic interplay. ⋯ Aging did not affect either the density or layer-specific distribution of CB1 cannabinoid receptor-immunoreactive processes. We concluded that organizing principles of CB1 cannabinoid receptor-containing neurons and their terminal fields within the basal forebrain are evolutionarily conserved between rodents and prosimian primates. In contrast, the areal expansion and cytoarchitectonic differentiation of neocortical subfields in primates is associated with differential cortical patterning of CB1 cannabinoid receptor-containing subcortical and intracortical afferents.
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Basic fibroblast growth factor (bFGF) is an important mitogen and neurotrophic factor that binds and signals through the high-affinity receptor, fibroblast growth factor receptor 1 (FGFR1). However, only a limited amount of information is available concerning the molecular forms and anatomical distribution of fibroblast growth factors (FGFs) in the normal human brain. We found multiple bFGF and FGFR1 mRNA transcripts which vary in expression pattern across human brain regions. ⋯ In contrast to FGFR1, bFGF mRNA expression was detected at very low levels in a small fraction of the neurons in the human hippocampus and caudal ERC. While bFGF mRNA may be expressed at low levels in neurons, bFGF-immunopositive cells with astrocytic features were detected throughout the mesial temporal lobe in rats, monkeys and humans. bFGF immunoreactive processes are found traversing the dentate gyrus, and bFGF immunoreactive cells are found in the neurogenic subgranular zone in all three mammalian species studied. The anatomical distribution of these two FGF family members suggests that bFGF is endogenously positioned to be involved in ongoing neurogenesis in the adult hippocampus, and that FGF trophic signaling to differentiated neurons could involve the release of astrocytic bFGF acting on neuronal FGFR1 in the normal adult human hippocampus.
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During spinal cord maturation neuronal excitability gradually differentiates to meet different functional demands. Spontaneous activity, appearing early during spinal development, is regulated by the expression pattern of ion channels in individual neurons. While emerging excitability of embryonic motoneurons has been widely investigated, little is known about that of spinal interneurons. ⋯ Patch clamp recordings confirmed these data, showing that ventral interneurons expressed functional ERG currents only transiently. Similar expression of the erg genes was observed at comparable ages in vivo. The role of ERG currents in regulating neuronal excitability during the earliest phases of spinal circuitry development will be examined in future studies.
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Subthalamic nucleus (STN) is a target of choice for the neurosurgical treatment of Parkinson's disease (PD). The therapeutic effect of STN lesion in PD is classically ascribed to the rescue of physiological activity in the output structures of the basal ganglia, and little is known about the possible involvement of the striatum. ⋯ We show that the beneficial motor effects produced in parkinsonian rats by STN lesion or l-DOPA therapy were paralleled by the normalization of overactive frequency and amplitude of striatal glutamate-mediated spontaneous excitatory postsynaptic currents (sEPSCs). Since neither l-DOPA treatment nor STN lesion affected sEPSCs kinetic properties, the reversal of these abnormalities in striatal excitatory synaptic transmission can be attributable to the normalization of glutamate release.