Neuroscience
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Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. ⋯ Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early.
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The involvement of the prefrontal cortex in pain processing has been recently addressed. We studied the role of the infralimbic cortex (IL) and group I metabotropic glutamate receptors (mGluRs) in descending modulation of nociception in control and monoarthritic (ARTH) conditions. Nociception was assessed using heat-induced paw withdrawal while drugs were microinjected in the IL of rats. ⋯ Finally, mGluR5 but not mGluR1 antagonists blocked the pronociceptive action of GLU in both groups. The results indicate that IL contributes to descending modulation of nociception. mGluR5 in the IL enhance nociception in healthy control and monoarthritic animals, an effect that is tonic in ARTH. Moreover, activation of IL mGluR1s attenuates nociception following the development of monoarthritis.
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MicroRNAs (miRNAs) inhibit RNA targets and may contribute to postpartum central nervous system (CNS) gene expression changes, although this has never been tested. In the present study, we directly evaluated miRNA levels using RNA sequencing during reproduction in female mice in the lateral septum (LS). We found the reliable and robust changes of miRNAs away from the virgin stage at the three other stages, namely pregnant, day 1 postpartum, and day 8 postpartum. ⋯ Previously published postpartum LS gene expression changes were enrichment for LS miRNA targets, as expected. Surprisingly, postpartum gene expression changes from other regions were also enriched against LS miRNA targets, suggesting a core group of miRNAs may act across the CNS during reproduction. Together, we directly examine miRNAs and find significant alterations in the postpartum brain.
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While the regulation of the neurogenesis and oligodendrogenesis by microRNAs has been intensively studied, little is known about the role of microRNAs (miRNAs) in the development of astrocytes. Here, we report that microRNAs play an essential role in the differentiation and maturation of white matter astrocytes in mouse spinal cord tissues. ⋯ In contrast, the expression of gray matter protoplasmic astrocyte marker was not affected. Together, our studies indicated that miRNAs are required for the differentiation and morphological maturation of white matter fibrous astrocytes in the developing spinal cord.
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During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. ⋯ Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms.