Neuroscience
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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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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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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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Brain activities in response to acupuncture have been investigated in multiple studies; however, the neuromechanisms of low- and high-frequency transcutaneous electric acupoint stimulation (TEAS) analgesia are unclear. This work aimed to investigate how brain activity and the analgesic effect changed across 30-min low- versus high-frequency TEAS. Forty-six subjects received a 30-min 2, 100-Hz TEAS or mock TEAS (MTEAS) treatment on both behavior test and functional magnetic resonance imaging (fMRI) scan days. ⋯ In both TEAS groups, the regional CBF revealed a trend of early activation with later inhibition; also, a positive correlation between analgesia and the regional CBF change was observed in the anterior insula in the early stage, whereas a negative relationship was found in the parahippocampal gyrus in the later stage. The TEAS analgesia was specifically associated with the default mode network and other cortical regions in the 2-Hz TEAS group, ventral striatum and dorsal anterior cingulate cortex in the 100-Hz TEAS group, respectively. These findings suggest that the mechanisms of low- and high-frequency TEAS analgesia are distinct and partially overlapped, and they verify the treatment time as a notable factor for acupuncture studies.
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This study investigated the influence of vision and proprioception on the excitability of direct corticospinal (corticomotoneuronal) pathway to the soleus in young and elderly adults during upright standing. Ten young and 10 elderly adults stood upright on a rigid surface with eyes open or closed, and on foam mat with eyes open. The corticomotoneuronal excitability was investigated by assessing facilitation of the soleus H-reflex induced by subthreshold transcranial magnetic stimulation (TMS). ⋯ However, the amplitude of the H reflex conditioned by TMS relative to the amplitude of the test H reflex ratio was positively associated with EMG activity of the plantar flexor muscles during upright standing (r(2)=0.47; p<0.001). These results indicate that regardless of age the excitability of the corticomotoneuronal pathway is not modulated with changes in the sensory conditions during upright standing. Nonetheless, the corticomotoneural drive to control leg muscle during upright standing increases with the level of soleus muscle activity.