Neuroscience
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Autism Spectrum Disorder (ASD) is often found to co-exist with non-core behavioral manifestations that include difficulties in disengagement of attention to sensory cues. Here we examined whether this behavioral abnormality can be induced in rats prenatally exposed to valproic acid (VPA), a well-established teratogen associated with ASD animal models. We tested rats using an auditory-cued sensorimotor task (ACST) based on the premise that ACST will be more sensitive to developmental changes in temporal association cortex (TeA) of the posterior attention system. ⋯ However, both control and VPA-treated rats performed similarly when tested on novel object recognition (NOR) and novel context mismatch (NOCM) behavioral tasks that are known to be sensitive to normal perirhinal and prefrontal network functioning respectively. Consistent with disrupted posterior rather than frontal networks, we also report that VPA can selectively act on deep-layer TeA cortical neurons by showing that VPA increased dendritic density in isolated deep-layer TeA but not frontal neurons. These results describe a useful approach to examine the role of cue-dependent control of attention systems in rodent models of autism and suggest that disengagement impairments may arise from an inability to modify behavior through the appropriate use of sensory cue associations.
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Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. ⋯ Increased concentrations of dopamine and its metabolites, serotonin (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.
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Apoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM's role in cerebral I/R and its potential mechanism. ⋯ These results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.
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Leucine-rich repeat in Flightless-1 interaction protein 1 (Lrrfip1) is an up-regulated protein after cerebral ischemia whose precise role in the brain both in healthy and ischemic conditions is unclear. Different Lrrfip1 isoforms with distinct roles have been reported in human and mouse species. The present study aimed to analyze the Lrrfip1 transcriptional variants expressed in rat cortex, to characterize their expression patterns and subcellular location after ischemia, and to define their putative role in the brain. ⋯ The main isoform, Lrrfip1, was found to be up-regulated from the acute to the late phases of ischemia in the cytoplasm of neurons and astrocytes of the peri-infarct area. This study demonstrates that Lrrfip1 activates β-catenin, Akt, and mammalian target of rapamycin (mTOR) proteins in astrocytes and positively regulates the expression of the excitatory amino acid transporter subtype 2 (GLT-1). Our findings point to Lrrfip1 as a key brain protein that regulates pro-survival pathways and proteins and encourages further studies to elucidate its role in cerebral ischemia as a potential target to prevent brain damage and promote functional recovery after stroke.
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The distribution and functional presence of three voltage-dependent potassium channels, Kv2.1, Kv3.4, Kv4.3, respectively, were studied in the central nervous system of the snail Helix pomatia by immunohistochemical and electrophysiological methods. Cell clusters displaying immunoreactivity for the different channels were observed in all parts of the CNS, although their localization and number partly varied. Differences were also found in their intracellular, perikaryonal and axonal localization, as well as in their presence in non-neuronal tissues nearby the CNS, such as the perineurium and the aorta wall. ⋯ Voltage-clamp recordings proved that outward currents obtained from neurons displaying Kv3.4 or Kv4.3 immunoreactivity contained transient components while Kv2.1 immunoreactive cells were characterized by delayed currents. The distribution of the K(+)-channels containing neurons suggests specific roles in intercellular signaling processes in the Helix CNS, most probably related to well-defined, partly local events. The cellular localization of the K(+)-channels studied supports their involvement in both pre- and postsynaptic events at perikaryonal and axonal levels.