Neuroscience
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Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe amino acid excitotoxicity. The aim of this study was to explore the neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates EAAT2, against EBI and the potential mechanisms using in vitro experiments and a rat model of SAH. Intracisternal treatment with CEF significantly improved neurological outcomes and alleviated extracellular glutamate accumulation after SAH. ⋯ In Morris water maze (MWM) tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in spatial learning memory and reference memory. CEF promoted the nuclear translocation of p65 as well as the activation of Akt in hippocampal astrocytes in vitro and in vivo. These findings suggest that CEF may exert significant protective effects against EBI following SAH by modulating the PI3K/Akt/NF-κB signaling pathway.
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Abnormalities of mental status represent a severe complication and an important cause of death in acute pancreatitis (AP), which is characterized by a pattern of neurological signs and symptoms. As some of the symptoms of AP are also affected by catecholamine neurotransmitters, they cannot be ruled out of the pathophysiology of AP; however, little research has been performed exploring this hypothesis. Our study aimed to elucidate whether AP affects the metabolism of catecholamine neurotransmitters in rats. ⋯ The MAO-A and TH protein concentrations of the 6-h and 24-h groups also decreased. The other catecholamine concentration and enzyme activities fluctuated, but there was no statistically significant difference compared with the control group. Catecholamine neurotransmitter metabolic systems are widely affected in AP, and these fluctuations may play an important role in determining the symptomatology of AP.
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Interactions between the prelimbic cortex and the basolateral amygdala underlie fear memory processing, mostly through acquiring and consolidating the learning of a conditioned fear. More recently, studies highlighted the role of the dorsal periaqueductal gray (DPAG) in the modulation of learning fear responses. In addition, extensive data in the literature have signaled the importance of serotonin (5-HT) on fear and anxiety. ⋯ In these regions LA but not HA rats were susceptible to the anxiolytic-like effect of 5-HT1A receptor activation. It is thought that the expression of conditioned fear in HA subjects may be dependent on other 5-HT receptors, as the 5-HT1B subtype, and/or changes in other systems such as the GABA and glutamate neurotransmitters. These results increase our understanding of the rostrocaudal influence of 5-HT on the unconditioned and conditioned fear responses in LA and HA subjects and, to some extent, are in disagreement with the theoretical current that emphasizes the role of 5-HT on anxiety, mainly at the subcortical and midbrain levels.
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Bryostatin-1, a potent agonist of protein kinase C (PKC), has recently been found to enhance spatial learning and long-term memory in rats, mice, rabbits and the nudibranch Hermissenda, and to exert profound neuroprotective effects on Alzheimer's disease (AD) in transgenic mice. However, details of the mechanistic effects of bryostatin on learning and memory remain unclear. To address this issue, whole-cell recording, a dual-recording approach and extracellular recording techniques were performed on young (2-4months) Brown-Norway rats. ⋯ In addition, 8-[2-(2-pentyl-cyclopropylmethl)-cyclopropyl]-octanoic acid (DCP-LA), a selective PKCε activator, also increased the frequency and amplitude of sIPSCs. Taken together, these results suggest that bryostatin enhances GABAergic neurotransmission in pyramidal neurons by activating the PKCα & ε-dependent pathway and by a presynaptic mechanism with excitation of GABAergic interneurons. These effects of bryostatin on GABAergic transmissions and modifiability may contribute to the improvement of learning and memory previously observed to be induced by bryostatin.
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5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of the rhesus macaque prefrontal cortex. ⋯ Furthermore, we found that early-life maternal deprivation is associated, in the adult monkey cortex, with DNA hydroxymethylation changes of promoters of genes related to neurological functions and psychological disorders. These results reveal that early social adversity triggers variations in brain DNA hydroxymethylation that could be detected in adulthood.