Byung Sun Kim

Intracellular gold nanoparticles increase neuronal excitability and aggravate seizure activity in the mouse brain.

Due to their inert property, gold nanoparticles (AuNPs) have drawn considerable attention; their biological application has recently expanded to include nanomedicine and neuroscience. However, the effect of AuNPs on the bioelectrical properties of a single neuron remains unknown. Here we present the effect of AuNPs on a single neuron under physiological and pathological conditions in vitro. AuNPs were intracellularly applied to hippocampal CA1 neurons from the mouse brain. The electrophysiological property of CA1 neurons treated with 5- or 40-nm AuNPs was assessed using the whole-cell patch-clamp technique. Intracellular application of AuNPs increased both the number of action potentials (APs) and input resistance. The threshold and duration of APs and the after hyperpolarization (AHP) were decreased by the intracellular AuNPs. In addition, intracellular AuNPs elicited paroxysmal depolarizing shift-like firing patterns during sustained repetitive firings (SRF) induced by prolonged depolarization (10 sec). Furthermore, low Mg2+-induced epileptiform activity was aggravated by the intracellular AuNPs. In this study, we demonstrated that intracellular AuNPs alter the intrinsic properties of neurons toward increasing their excitability, and may have deleterious effects on neurons under pathological conditions, such as seizure. These results provide some considerable direction on application of AuNPs into central nervous system (CNS).

Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models.

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex.

RationaleThe aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known.ObjectivesWe investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity.MethodsAn observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D1 receptor antagonist), or haloperidol (DA D2 receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo.ResultsThe microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment.ConclusionsThe current results demonstrated that DA D2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.

Tracing the evolution of multi-scale functional networks in a mouse model of depression using persistent brain network homology

Many brain diseases or disorders, such as depression, are known to be associated with abnormal functional connectivity in neural networks in the brain. Some bivariate measures of electroencephalography (EEG) for coupling analysis have been used widely in attempts to explain abnormalities related with depression. However, brain network evolution based on persistent functional connections in EEG signals could not be easily unveiled. For a geometrical exploration of brain network evolution, here, we used persistent brain network homology analysis with EEG signals from a corticosterone (CORT)-induced mouse model of depression. EEG signals were obtained from eight cortical regions (frontal, somatosensory, parietal, and visual cortices in each hemisphere). The persistent homology revealed a significantly different functional connectivity between the control and CORT model, but no differences in common coupling measures, such as cross correlation and coherence, were apparent. The CORT model showed a more localized connectivity and decreased global connectivity than the control. In particular, the somatosensory and parietal cortices were loosely connected in the CORT model. Additionally, the CORT model displayed altered connections among the cortical regions, especially between the frontal and somatosensory cortices, versus the control. This study demonstrates that persistent homology is useful for brain network analysis, and our results indicate that the CORT-induced depression mouse model shows more localized and decreased global connectivity with altered connections, which may facilitate characterization of the abnormal brain network underlying depression.

Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy

Many patients with epilepsy are afflicted with psychiatric comorbidities including social dysfunction. However, although social deficits have been a major concern in epilepsy treatment, the relationship between social behavioral pathogenesis and the time course of epileptogenesis is not well defined. To address this, we investigated social behavioral alterations and cortical rhythms during two distinct periods in a mouse model of temporal lobe epilepsy (TLE): 1) a seizure-free, latent period after status epilepticus and 2) the subsequent, chronic period characterized by spontaneous recurrent seizures (SRSs). We found that severe social impairments, such as reduced sociability/social novelty preference, social interaction, social learning, and enhanced defensiveness, appeared during the latent period in mice with TLE. The social dysfunctions in the latent-period mice were nearly comparable to those in the chronic-period mice. We also found that both the latent- and chronic-period mice showed similar aberrant neural activities. They showed enhanced delta-band (1-4 Hz) activity and reduced alpha- (8.5-12 Hz) and gamma-band (30-55 Hz) activity during baseline behavior. Interestingly, concomitant increases in alpha- and gamma-band activities during social behavior, which were characteristic in control mice, were not observed in either latent- or chronic-period mice. Our results indicate that social deficits and abnormal neural activities appear at an earlier stage in epileptogenesis regardless of SRS occurrence. These findings may help to understand behavioral pathogenesis in patients with TLE and at-risk patients with initial insults that develop into TLE.

The immunosuppressant cyclosporin A inhibits recurrent seizures in an experimental model of temporal lobe epilepsy

The immunosuppressant, cyclosporin A (CsA), is neuroprotective following brain injury. Previous studies suggest that CsA treatment ameliorates seizure severity during status epilepticus (SE) or cell death following SE. The antiepileptic effects of CsA on recurrent seizures, however, have not been investigated. In the present study, the effects of CsA on spontaneous recurrent seizures (SRSs) in a kainate (KA)-induced mouse model of mesial temporal lobe epilepsy (TLE) were examined. Moreover, the effects of CsA on epileptiform activity in a 4-aminopyridine (4-AP)-induced in vitro seizure model were investigated. A mesial TLE mouse model was generated with a unilateral intrahippocampal injection of KA. SRSs were determined in the ipsilateral hippocampal CA1 region with a long-term video-EEG. CsA was systemically administrated to the epileptic mice exhibiting a stable occurrence of SRSs. A 1-mg/kg dose of CsA did not have any effect on SRSs in the epileptic mice. However, a 5-mg/kg dose of CsA significantly reduced the number of SRSs and decreased the severity of the seizures in the epileptic mice. Additionally, CsA treatment inhibited spontaneous burst discharges in 4-AP-treated hippocampal slices. The results of the present study demonstrate that CsA inhibits recurrent seizures in a mouse model of mesial TLE and suggest that CsA may afford both neuroprotection against SE and antiepileptic effects during the chronic period of epilepsy.

Free radical grafting of styrene onto polyethylene in intensive mixer

The graft copolymerization of styrene onto low density polyethylene (LDPE) with dicumyl peroxide as an initiator was studied. The existence of the graft copolymer was verified by infrared spectra. The effects of the initiator concentration, the feed composition, the reaction time, and the reaction temperature were discussed. Grafting efficiency reached a maximum value with the increase of reaction time. The effect of increasing the concentration of dicumyl peroxide was to decrease the grafting efficiency up to a minimum value. Grafting efficiency was not affected much by the variation of the reaction temperature. Grafting efficiency decreased largely with the increase of the feed composition of styrene. The compatibilizing effect of the copolymer prepared in this study was demonstrated by the morphology and mechanical properties of high impact polystyrene/LDPE blends.

Social deficits in the AY-9944 mouse model of atypical absence epilepsy

Atypical absence epilepsy (AAE) showing slow spike-and-wave discharges (SWD) is characterized by severely abnormal cognition and neurodevelopmental or neurological outcomes in humans. However, despite the severe behavioral outcomes in AAE, the relationship between AAE and social-behavioral dysfunctions has not defined well, either experimentally or in patients with AAE. Experimentally, AAE can be produced by administering AY-9944 (AY), a cholesterol biosynthesis inhibitor. In this study, we characterized social behavior in the AY mouse model of AAE. AAE in the mouse was induced by repeated postnatal administration of AY every 6 days from postnatal day (P) 2 to P20. AY-treated mice exhibited spontaneous, recurrent, and synchronous SWD (4-5 Hz) in electroencephalographic recordings. AY-treated mice performed tasks involving sociability/social novelty preference, social interaction with a juvenile conspecific, observational fear, and resident-intruder aggression. They showed behavioral dysfunction in social interactions with a juvenile conspecific and sociability/social novelty preference tasks. They also exhibited reduced social fear learning in observational fear conditioning. Interestingly, they showed increased levels of offensive behaviors in a resident-intruder task. However, AY-treated mice displayed normal levels of anxiety in light/dark transition and the elevated plus maze tasks, and showed slightly increased locomotor activity in an open-field task. These results demonstrate social dysfunction in the AY-induced AAE model. Our study of social behavior can also provide valuable information about Lennox-Gastaut syndrome, in which AAE is a component. Thus, our findings may help to understand behavioral pathogenesis or characteristics of patients with AAE.