• Journal of Genetic Medicine
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• v.13 no.1
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• pp.1-13
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• 2016

Although some mutations are beneficial and are the driving force behind evolution, it is important to maintain DNA integrity and stability because it contains genetic information. However, in the oxygen-rich environment we live in, the DNA molecule is under constant threat from endogenous or exogenous insults. DNA damage could trigger the DNA damage response (DDR), which involves DNA repair, the regulation of cell cycle checkpoints, and the induction of programmed cell death or senescence. Dysregulation of these physiological responses to DNA damage causes developmental defects, neurological defects, premature aging, infertility, immune system defects, and tumors in humans. Some human syndromes are characterized by unique neurological phenotypes including microcephaly, mental retardation, ataxia, neurodegeneration, and neuropathy, suggesting a direct link between genomic instability resulting from defective DDR and neuropathology. In this review, rare human genetic disorders related to abnormal DDR and damage repair with neural defects will be discussed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.108-115
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• 2006

The inherent biology of neural stem cells (NSCs) endows them with capabilities that not only circumvent many of the limitations of other gene transfer vehicles, but that enable a variety of novel therapeutic strategies heretofore regarded as beyond the purview of neural transplantation, Most neurodegenerative diseases are characterized not by discrete, focal abnormalities but rather by extensive, multifocal, or even global neuropathology. Such widely disseminated lesions have not conventionally been regarded as amenable to neural transplantation. However, the ability of NSCs to engraft diffusely and become integral members of structures throughout the host CNS while also expressing therapeutic molecules may permit these cells to address that challenge. Intriguingly, while NSCs can be readily engineered to express specified foreign genes, other intrinsic factors appear to emanate spontaneously from NSCs and, in the context of reciprocal donor-host signaling, seem to be capable of neuroprotective and/or neuroregenerative functions. Stem cells additionally have the appealing ability to "home in" on pathology, even over great distances. Such observations help to advance the idea that NSCs - as a prototype for stem cells from other solid organs - might aid in reconstructing the molecular and cellular milieu of maid eve loped or damaged organs.

• BMB Reports
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• v.53 no.1
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• pp.20-27
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• 2020

Translocator protein (TSPO), also known as peripheral benzodiazepine receptor, is a transmembrane protein located on the outer mitochondria membrane (OMM) and mainly expressed in glial cells in the brain. Because of the close correlation of its expression level with neuropathology and therapeutic efficacies of several TSPO binding ligands under many neurological conditions, TSPO has been regarded as both biomarker and therapeutic target, and the biological functions of TSPO have been a major research focus. However, recent genetic studies with animal and cellular models revealed unexpected results contrary to the anticipated biological importance of TSPO and cast doubt on the action modes of the TSPO-binding drugs. In this review, we summarize recent controversial findings on the discrepancy between pharmacological and genetic studies of TSPO and suggest some future direction to understand this old and mysterious protein.

• Journal of Veterinary Science
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• v.23 no.2
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• pp.30.1-30.6
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• 2022

This report aims to describe the first case of muscular and collagenous choristoma in a dog. A 10-yr-old female mixed-breed dog presented with lateral recumbence, vocalization, positional vertical nystagmus, divergent strabismus, anisocoria, and status epilepticus. The clinical condition evolved to stupor and ultimately, death. Necropsy revealed a white mass causing an irregular increase in the volume of the cerebellar vermis. In histological analysis, a well circumscribed, unencapsulated mass was observed in the cerebellum, consisting of fibers of striated skeletal muscle and collagen fibers, mostly mineralized. Based on the histopathological and histochemical findings, a diagnosis of muscular and collagenous cerebellar choristoma was made.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7385-7393
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• 2013

Background: Only few epidemiological data on primary central nervous system (CNS) tumors in Shanghai have been reported. Methods: All cases of primary CNS tumors that were registered at Center for Disease Control and Prevention (CDC) were collected (1973-2007: urban Shanghai; 2003-2007: whole Shanghai city). Trends were analyzed using joinpoint analysis and rates were stratified by age, gender and region. Histological data were collected from both CDC and Huashan Hospital. Results: From 1973 to 2007, the five-year average incidence rate in urban Shanghai increased in both genders, especially in the elderly population. Joinpoint analysis showed the age-adjusted incidence rate for males increased first but then plateaued, whilst rates for females continued increasing over the 35 years. For the five-year status quo (2003-2007), rural had a higher age-adjusted incidence rate than urban populations, and females higher than males, especially those with advanced age. According to CDC (2003-2007) and Huashan Hospital (1951-2011), the two most common histological subtypes were neuroepithelial tumors (with male predominance) and meningiomas (with female predominance). Conclusions: In Shanghai, a steadily increased incidence rate of primary CNS tumors was observed in general, and in the elderly and female population in particular.

• BMB Reports
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• v.53 no.4
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• pp.234-239
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• 2020

Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures and caused by various factors and mechanisms. Malfunction of the olfactory bulb is frequently observed in patients with epilepsy. However, the morphological changes in the olfactory bulb during epilepsy-induced neuropathology have not been elucidated. Therefore, in the present study, we investigated the expression of parvalbumin (PV), one of the calcium-binding proteins, and morphological changes in the rat main olfactory bulb (MOB) following pilo-carpine-induced status epilepticus (SE). Pilocarpine-induced SE resulted in neuronal degeneration in the external plexiform layer (EPL) and glomerular layer (GL) of the MOB. PV immunoreactivity was observed in the neuronal somas and processes in the EPL and GL of the control group. However, six hours after pilocarpine administration, PV expression was remarkably decreased in the neuronal processes compared to the somas and the average number of PV-positive interneurons was significantly decreased. Three months after pilocarpine treatment, the number of PV-positive interneurons was also significantly decreased compared to the 6 hour group in both layers. In addition, the number of NeuN-positive neurons was also significantly decreased in the EPL and GL following pilocarpine treatment. In double immunofluorescence staining for PV and MAP2, the immunoreactivity for MAP2 around the PV-positive neurons was significantly decreased three months after pilocarpine treatment. Therefore, the present findings suggest that decreases in PV-positive GABAergic interneurons and dendritic density in the MOB induced impaired calcium buffering and reciprocal synaptic transmission. Thus, these alterations may be considered key factors aggravating olfactory function in patients with epilepsy.

• Toxicological Research
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• v.6 no.2
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• pp.191-204
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• 1990

Trimethyltin (TMT) induced lesions in the rat hippocampal formation was reviewed. Adult rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed between 3-60 days following exposure. On the hippocampal formation, the granule cells of fascia dentata showed early changes which subsided considerably at a later time when the destruction of the pyramidal neurons of the Ammon's horn became increasingly pronounced with time, leading to severe destruction of the structure. It is interesting to note that there was an inverse relationship of pathological involvement between the f.d. granule cells and the Ammon's horn neurons; i.e., when there was a large sparing of the granule cells. there was an extensive damage to the Ammon's horn and vice versa. This inverse relationship was also true between the $CA_3$neurons and the $CA_{1,2}$neurons in the Ammon's horn. Progressive zinc loss, as demonstrated by Timm's method, on the Mossy fibers was also observed. Similar Mossy fiber zinc depletion has been demonstrated in electrical stimulatory excitation condition of the perforant path to the hippocampus. Depletion of corticosterone, an inhibitor to the hippocampal neurons, by means of adrenalectomy will exaggerate the TMT induced hippocampal lesion. Neonatal study revealed that a unique degenerative pattern of the Ammon's horn could be established in accordance with exposure to TMT at specific maturation periods of the fippocampal formation: increasing destruction of the Ammon's horn with increasing synaptogenesis between the f.d. granule cells and the Ammon's horn neurons. Thus it is apparent that the damage of the Ammon's horn, upon exposure to TMT, may depend on the integrity and functional state of the f.d. granule cells. A hyperexcitory scheme and mechanism as the toxicity basis of TMT in the hippocampal formation is proposed and discussed.

• Journal of Korean Neurosurgical Society
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• v.30 no.7
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• pp.842-848
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• 2001

Objectives : The mortality rate of subarachnoid hemorrhage(SAH) has been reduced recently due to refinement of microsurgical technique and improved perioperative management. Also, many survivors of SAH show excellent neurological recoveries. However, we found that a high proportion of the survivors do not fully regain their premorbid status in cognitive and memory function. Object of this study is to evaluate which factors might influence on cognitive and memory impairment in ruptured aneurysmal SAH patients. Methods : In this prospective study, a series of 66 patients with aneurysmal subarachnoid hemorrhage(SAH) from 1996 to 1998, most of whom had a "good" or "fair" neurological outcome, were assessed with various tests of cognition and memory function. All patients underwent clipping operation by pterional approach. Right side approach was performed in 16 case and left 21 cases. K-WAIS(Korean-Wechsler Adult Intelligence Scale) was used as method of cognition and memory function test. The time interval between SAH and assessment varied between 4 months and 8 months, averaging 6.2 months. Statistical analyses were carried out for each test score to see whether aneurysm site(A-com : non A-com), route of approach, age and sex, vasospasm, Hunt-Hess grade and Fisher CT group at admission, Glasgow Outcome Scale(GOS) at discharge affect cognitive and memory function. Results : Aneurysm site was not shown to be associated with performance on any test, and the initial grade (Hunt-Hess grade, Fisher CT group) of SAH and vasospasm had only minimal predictive values. The grade at discharge( GOS) was proved to be the best predictor of impairment of cognition and memory function within 1 year after operation. Conclusion : The authors conclude that the diffuse effects of SAH are more important than focal neuropathology in relation to cognitive impairment in this group of patients.

• Toxicological Research
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• v.23 no.1
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• pp.33-38
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• 2007

Zinc is an endogenous transition metal that can be synaptically released during neuronal activity. However, zinc may contribute to the neuropathology associated with a variety of conditions. Carnosine expressed in glial cells can modulate the effects of zinc on neuronal excitability as a zinc chelator. We hypothesize that carnosine may protect against neurotoxicity of zinc in cortical neuronal cells. The cortical neuronal cells from newborn rats were prepared and exposed to zinc chloride and/or carnosine at various concentrations. Zinc at the doses of 0 to $500{\mu}M$ decreased neuronal cell viability in a dose-dependent manner. Additionally, at the concentrations of 100 and $200{\mu}M$, it significantly decreased cell viability in an exposed time-dependent manner (p < 0.05). Treatment with carnosine at the concentrations of 20 and $200{\mu}M$ significantly increased neuronal cell proliferation by approximately 14% and 20%, respectively, compared to the control (p < 0.05). At the concentrations of 100 and $200{\mu}M$ zinc, $20{\mu}M$ carnosine significantly increased the viability of neuronal cells by 18.3% and 12.1 %, and $200{\mu}M$ carnosine also increased it by 33.5% and 28.6%, respectively, compared to the normal control group (p < 0.01). These results suggest that carnosine at a physiologically relevant level may protect against zinc-mediated toxicity in neuronal cells as an endogenous neuroprotective agent.