Neuroscience
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Attention deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric childhood disorder, characterized by hyperactivity, impulsivity and impaired attention, treated most frequently with methylphenidate (MPH). For children and adults with ADHD who do not respond satisfactorily or do not tolerate well stimulants such as MPH or D-Amphetamine, for them the alternative is to use Atomoxetine (ATX), a norepinephrine (NE) transporter inhibitor that increase extracellular NE. We examined the effects of ATX on behavior and hippocampal synaptic plasticity in the murine prenatal nicotine exposure (PNE) model of ADHD. ⋯ Paired-pulse ratios (PPR) were not significantly different for any condition. These results indicate that administration of ATX in a PNE model of ADHD reestablishes TBS-dependent LTP in CA3-CA1 synapses. The results suggest postsynaptic changes in synaptic plasticity as part of the mechanisms that underlie improvement of ADHD symptoms induced by ATX.
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The investigation on neurotransmission function during normal and pathologic development is a pivotal component needed to understand the basic mechanisms underlying neurodevelopmental pathologies. To study these diseases, many animal models have been generated which allowed to face the limited availability of human tissues and, as a consequence, most of the electrophysiology has been performed on these models of diseases. On the other hand, the technique of membrane microtransplantation in Xenopus oocytes allows the study of human functional neurotransmitter receptors thanks to the use of tissues from autopsies or surgeries, even in quantities that would not permit other kinds of functional studies. ⋯ Our findings retrace previous results and, in the light of this, further argue in favor of Prof. Miledi's technique of membrane microtransplantation that proves itself a very useful tool of investigation in the field of neurophysiology. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
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Accumulation of amyloid-β (Aβ) in brain tissue contributes to the pathophysiology of Alzheimer's disease (AD). We recently reported that intrahippocampal transplantation of mouse bone marrow-derived microglia-like (BMDML) cells suppresses brain amyloid pathology and cognitive impairment in a mouse model of AD. How these transplanted cells interact with resident microglia remains unknown. ⋯ Brain TGF-β1 levels and resident microglial TGF-β1R expression were increased by intrahippocampal injection of BMDML cells in a mouse model of AD. Cotreatment with the TGF-βR1 inhibitor suppressed the ability of transplanted BMDML cells to increase microglial TGF-β1R expression and decrease hippocampal Aβ levels. Taken together, these findings suggested that transplanted BMDML cells secreted TGF-β1 to stimulate Aβ phagocytosis by resident microglia and decrease brain Aβ pathology.
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White matter lesions are common when global cerebral ischemia (GCI) occurs in the elderly, and cause damage to neurological and psychological functions. Remyelination often fails because of the limited recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to mature oligodendrocytes (OLs). The activation of microglia, the most important immune cells in the central nervous system, and subsequent inflammation have been implicated in myelination repair disorder. ⋯ No effect was found on myelin in the corpus callosum. Besides, hippocampal neurons were protected by anti-FKR treatment after GCI. Collectively, our data demonstrated that downregulating of the Fractalkine/CX3CR1 signaling pathway had an anti-depressant and cognition-improvement effect by inhibiting microglia activation, promoting OPCs maturation and remyelination.
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Human visual function degrades with age. Previous studies of visual perception have shown that aged people have worse performance in the coding of orientation information. However, the neuronal mechanism still remains elusive. ⋯ Further investigation of neuronal correlation showed higher noise and signal correlations in aging monkeys than that in young monkeys. These correlation changes predicted a detrimental effect on the efficiency of population coding of orientation information. Taken together, our results suggest that the information coding efficiency of orientation information is impaired during aging and might account for the degradation of performance in human fine orientation discrimination task.