This study was carried out to identify synaptic reorganization by mossy fibers of epileptic dentate gyrus by Timm sulphide silver histochemistry and to investigate degree of synaptic reorganization according to both hippocampal sclerosis and epileptiform discharge in human temporal lobe epilepsy(TLE). The control group was composed of two hippocampal tissues obtained from autopsied brain without neurological abnormalities. TLE group was composed of thirteen hippocampal tissues obtained from surgically resected temporal lobe. Among thirteen hippocampal tissues, five specimens were obtained both of two areas of each hippocampus with or without prominent epileptiform discharges on electrocorticogram(ECoG) for tailored hippocampal resection. Hippocampal cell density was quantitatively analyzed in TLE group and compared with that of control group. A portion of hippocampal tissue was observed under light microscopic and transmission electron microscopes after development with Danscher method. The results were as follows : Hippocampal cell loss was noted in all TLE group. Hippocampal cell loss greater than 30% of control values was found in 12 cases and average hippocampal cell loss was 70%(range 39-88%). The remaining 1 case had 13% hippocampal cell loss. The supragranular Timm granules were noted in inner molecular layer of dentate gyrus and tended to significantly increase in proportion as severity of hippocampal sclerosis. Average of hippocampal cell loss in two areas of five hippocampal tissues with or without prominent epileptiform discharge on ECoG was 73.6%(range 53-90%) and 66.4%(range 50-86%), which showed statistically significant (p<0.05) difference between these two areas and the supragranular Timm granules also tended to increase in the hippocampal tissue with epileptiform discharge. On transmission electron microscope, there showed distinct supragranular Timm granules correspond to mossy fiber synaptic terminals. The results of this study demonstrated that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of human TLE and the development of mossy fiber synaptic reorganization is closely related to severity of hippocampal sclerosis. The result also support the rationale for tailoring the extent of hippocampal resection by intraoperative acute recording(ECoG) according to individual pathophysiology.
Brain ; Cell Count ; Dentate Gyrus* ; Epilepsy, Temporal Lobe* ; Hippocampus ; Humans ; Presynaptic Terminals ; Sclerosis* ; Silver ; Temporal Lobe*

OBJECTIVES: Alcoholism is known to be a heritable disease. It has been hypothesized that dopamineergic systems play an important heritable role in human behavor related to alcohol dependence, such as alcohol seeking. Therefore, genes involved in this pathway, including dopamine transporter(DAT1) which is responsible for taking released dopamine back up into presynaptic terminals and terminating dopaminergic activity, are potential candidate that may affect susceptibility to alcoholism. Analysis of a 40-base pair(bp)repeat(VNTR)in the 3'untranslated region of the DAT1 gene revealed variable number of the repeat ranging from 3 to 11 copies. Therefore, in the present study, we examined the association between alcoholism and VNTR polymorphism of DAT1. METHODS: Genomic DNA analysis with polymerase chain reaction(PCR)was used to identify the presence of a VNTR polymorphism. It was carried out within a group of 94 alcoholic patients and 113 normal controls. RESULTS: 1)There were no significant differences in allelic or genotype frequencies between the group of alcoholic patients and controls. 2)There were no significant differences in the first drinking age, onset age and latency of alcoholism according to DAT1 genotypes. 3)There was a significant difference in allelic frequencies between alcoholics with family history and those without family history. CONCLUSIONS: These results suggested that VNTR polymorphism of DAT1 is unlikely to be a factor in the genetic etiology of alcoholism, but might be related to familial transmission of alcoholism.
Age of Onset ; Alcoholics ; Alcoholism* ; DNA ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Drinking ; Genotype ; Humans ; Presynaptic Terminals

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.
Animals ; Astrocytes ; Axons ; Chronic Pain ; Oligodendroglia ; Presynaptic Terminals ; Regeneration ; Spinal Cord ; Spinal Nerve Roots ; Synapses

An attempt has been made to discriminate synaptic diversity in the neostriatum of the cat with emphasis on the characteristic structures of axon terminals and postsynaptic profiles. The differentiation of the axon terminals was based on the size and shape of synaptic vesicles in the axoplasm. Three types of axon terminals could be differentiated: Type I, the terminals contained small round (45 nm in diameter) vesicles; type II, the terminals with large pleomorphic (50 nm) vesicles; and type III, the terminals contained flattened (45 x 25 nm) vesicles. The type I terminals were making asymmetrical or symmetrical synapses in contact with the somata, dendrites and dendritic spines of neurons in the neostriatum, and a few type I terminals making asymmetrical or symmetrical contact with axons were also observed. The type II and III terminals were making symmetrical contact with the somata and dendrites of neostriatal neurons. A few type II terminals formed at the node of Ranvier of myelinated nerve fibers were making symmetrical contact with large dendrites. Additionally, dendro-dendritic and serial syanpses were rarely found in the neostriatum. In the serial synapses composed of axo-dendritic and dendro-dendritic synapses, the type I terminals making asymmetrical contact and the type II making symmetrical contact were identified.
Animals ; Axons ; Cats* ; Dendrites ; Dendritic Spines ; Neostriatum* ; Nerve Fibers, Myelinated ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

Although the distribution of locus ceruleus terminals has been demonstrated in the fundus striati[nucleus accumbens septi] by light microscopy[Jones & Moore, 1977 ; Mason & Fibiger, 1979 ; Streit or et al., 1979 ; Groenewegen et al., 1980], the synaptic organization of its terminals was not clarified. The purpose of the present investigation was to demonstrate the direct monosynaptic connection of the locus ceruleus terminals to the neuronal elements of the fundus stirati, and to clarify the synaptic structures of its terminals by electron microscopy two days after unilateral electric coagulation of the locus ceruleus. In the ipsilateral fundus striati, many axon terminals undergone dark degeneration were observed. These degenerating terminals containing small clear vesicles have asymmetric synaptic contacts with dendritic spines. Already two days after locus ceruleus lesion, distinct features of terminal degenerations appeared in the fundus striati ; enlarged axon terminals with altered synaptic vesicles, decrease of synaptic vesicles detached from the synaptic site, multiplication of dense bodies and infiltration of floccular material. At the same time, a regressive change occurred in which astrocytic processes encircled totally degenerated synapses spiraled around the synaptic remnants. These observations indicate that monosynaptic noradrenertic afferent connections to the fungus striati are confirmed, and the locus ceruleus terminals characterized by small round vesicles might be formed asymmetrical axo-spinous synapses with spiny neurons in the fundus striati.
Animals ; Cats* ; Dendritic Spines ; Fungi ; Locus Coeruleus* ; Microscopy, Electron ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

The presence of the zinc ion pump antibody ZnT-3 in zinc enriched (ZEN) cerebellar axonal terminals was detected in immunohistochemical sections of mouse cerebellum. All the ZnT-3-immunoreactive structures appeared punctate in the cerebellar cortex, while the white matter including intrinsic nuclei were void. The staining intensity varied in the different phylogenetic divisions of cerebellum. Archicortex was stained most intensively while paleo and in particular neocortex was stained only faintly. The ZnT-3 fraction was detected mainly in the upper half of the granule cell layer (GCL), although where they appeared ultrastructurally in small folded varicosities located corresponding to axon terminals of the Golgi cells. In the molecular layer (ML), the ZnT-3 staining was found to be distributed diffusely but in perpendicular radiating pattern through the layer but with the most intense staining in the upper half of the layer. Ultrastructurally the coarse patches of staining found in the granule cell layers were corresponded to presynaptic axon terminals contacting with granule cells. No ZnT-3 staining was observed in the Purkinje cell layer. The present results suggest that the Golgi cells in the mouse cerebellum are one of the ZEN neurons in the mammalian brain. In conclusion, we first showed putative ZEN terminals in the mouse cerebellum. These results will provide a valuable aid for investigation of further localization of the ZEN neurons in the mammalian cerebellum. More work is needed to further characterize the ZEN terminals, and so autometallographical studies are currently being investigated in this laboratory.
Animals ; Axons ; Brain ; Cerebellar Cortex ; Cerebellum* ; Ion Pumps ; Mice* ; Neocortex ; Neurons ; Presynaptic Terminals ; Zinc*

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been reported to play important roles in the regulation of olfactory information in the mammarian olfactory bulb. Although the distribution of nitric oxide synthase (NOS)-immunoreactive neurons in the olfactory bulb in the rat and other animals have been investigated by light microscopy, ultrastructures of the synaptic organization between NOS-immunoreactive neurons have not been studied yet. This study was conducted in order to identify NOS- immunoreactive neurons in the rat olfactory bulb and to define their synaptic organizations under the electron microscope using the preembedding immunocytochemical method which utilizes anti-NOS antiserum. MATERIALS AND METHODS: The olfactory bulbs of the rats were cut into 50 micromiter thick vertical sections and immunostained using the ABS method. Stained sections were observed under the light microscope. Some of the stained sections, additionally stained with uranyl acetate and dehydrated, were embedded in Epon 812 and prepared into 80 nm thick sections to be observed under the electron microscope. RESULT: NOS-immunoreactive neurons of the rat olfactory bulb made up 25.0% of periglomerular cells and 18.9% of granule cells. NOS-immunoreactive periglomerular cells received synaptic input from unlabeled axon terminals of the olfactory nerve and unlabeled periglomerular cells within the glomeruli. The output targets of NOS immunoreactive periglomerular cells were unlabeled axon terminals of the olfactory nerve and unlabeled periglomerular cells. NOS-immunoreactive granule cells received synaptic input from unlabeled processes of granule cells and axon terminals of mitral cells, and made output synapses onto the unlabeled axon terminals of mitral cells. CONCLUSION: NOS-immunoreactive neurons are periglomerular cells and granule cells, and NO liberated from NOS cells may play important roles in the modulation of olfactory transmission.
Animals ; Microscopy ; Neurons* ; Nitric Oxide Synthase* ; Nitric Oxide* ; Olfactory Bulb ; Olfactory Nerve ; Presynaptic Terminals ; Rats* ; Synapses

Morphological development of the ciliary body was studied by electron microscope in human fetuses from 50 to 260 mm crown-rump length(11-30 weeks of gestational age). At a 50 mm(11 weeks) fetus, the anlage of ciliary body was not appeared. At a 70 mm(13 weeks) fetus, the anlage of ciliary epithelium was appeared as the folds were formed by invaginating vessels in the basal surface of pigmented epithelium at the rim of optic cup. At the time, the anlage of ciliary muscle was formed as the mesenchymal cells, which located between the rim of optic cup and the scleral condensation, different-iate into the myoblasts, and the unmyelinated nerve fibers and the axon terminals were found in the interstitial tissue of mesenchyme. At 100-260 mm(15-30 weeks) fetuses, the myoblasts of ciliary body continued to develop into typical smooth muscle cells. At 200-260 mm(20-30 weeks) fetuses, the well-developed infoldings in the basal lamina and the well-developed interdigitations in the lateral sur-face were observed at both pigmented and nonpigmented epithelia. At the time, ganglion cells, Schwan cells and axon terminals were observed in the interstitial tissue of ciliary muscle.
Basement Membrane ; Ciliary Body* ; Epithelium ; Fetus* ; Ganglion Cysts ; Humans* ; Mesoderm ; Myoblasts ; Myocytes, Smooth Muscle ; Nerve Fibers, Unmyelinated ; Presynaptic Terminals

Recent studies have revealed that mossy fiber(MF) axons of dentate granule cells undergo synaptic reorganization in both electrical kindling models of temporal lobe epilepsy (TLE) and human TLE. This synaptic reorganization has been demonstrated by Timm histochemistry which selectively labels synaptic terminals of MF because of unusually high zinc content. Of MF. In electrical kindling model and human TLE Timm granules were distributed throughout the supragranular layer of dentate gyrus where they are not normally present. These supragranular Timm granules are regarded as MF synaptic reorganization. Kindling model of generalized epilepsy can be made by repeated intraperitoneal injections of subconvulsive dosage of pentylenetetrazol (PTZ). The present study is designed to test the hypothesis that MF synaptic reorganization might be developed in PTZ kindling model In this study, the supragranular Timm granules by Timm histochemistry were scored and depth EEG was recorded in dentate gyrus of various stages of PTZ kindling rats. The scores of supragranular Timm granules were 0. 33+0.17 in stage I seizure (n=9) ; 0. 38 + 0. 14 in stage II seizure (n=13) ; 0. 44 + 0. 18 in stage III seizure (n=9) ; 1. 40+0.16 in 3 consecutive or total 5-7 stage TV or V seizure (n=10) ; 1. 86+ 0.26 in 7-10 consecutive or total 10-15 stage IV or V seizure (n=7) ; 2.50+0.22 in 1215 consecutive or total 20-30 stage IV or V seizure (n=6) ; and 0. 30+0.15 in salinen controls (n=lo). Statistical analysis showed the supragranular Timm scorwere significantly higher in stage IV or V seizure than in control and in stage 1, I or, I seizure (p<0.05 ), and tended to increase with increasing numbers of stage IV or V seizure. Depth EEG recording from dentate gyrus showed 6-9Hz rhythmic waves in saline injected control, single or polyspikes or normal waves during stage I seizure, 4-6Hz slow waves or spike-waves complexes lasting 1-2 seconds during stage II seizure, 4-6Hz slow waves or spike-waves complexes lasting 3-6 seconds during stage III seizure, 8-15Hz spikes lasting over 10 seconds during stage IV seizure and 10-30HZ spikes lastmg over 20 seconds durmg stage V seizure The results demonstrate the development of MF synaptic reorganization and a sound correlation between MF synaptic reorganization and the progression of the kindlmg phenomenon in PTZ kindling models. These findings suggest that MF synaptic reorganization might be a critical event underlying the development and . Maintenance of kindling phenomenon and epileptic state.
Animals ; Axons ; Dentate Gyrus* ; Electroencephalography ; Epilepsy, Generalized ; Epilepsy, Temporal Lobe ; Humans ; Injections, Intraperitoneal ; Pentylenetetrazole* ; Presynaptic Terminals ; Rats* ; Seizures ; Zinc

BACKGROUND: Zolmitriptan (Zomig) is a selective serotonin agonist at the 5-hydroxytryptamine (5-HT1B/1D) receptor that acts both centrally and peripherally in the trigeminal nucleus and axon terminals and at adjacent meningeal vessels. The clinical efficacy of zolmitriptan in adult migraine has been documented in several placebo-controlled studies, but not studied yet in Korea. METHODS: This multicenter, double-blind, placebo-controlled study was directed to evaluate the efficacy and tolerability of a single 2.5-mg dose of zolmitriptan for the acute treatment of a single moderate or severe migraine attack in Korean patients. A sample consisting of 129 outpatients was randomized to receive either zolmitriptan (n=67) or placebo (n=62). RESULTS: The headache response at 2 hours after treatment was significantly greater in patients receiving zolmitriptan than in patients receiving placebo (52.2% versus 30.7%, p<0.05). At 4 hours, the response rate in the zolmitriptan group (91.5%) was significantly higher than in the placebo group (65.6%; p<0.05). Among the nonheadache symptoms, phonophobia was more relieved in the zolmitriptan group than in the placebo group (p=0.038). There were no clinically serious adverse events that were judged by the physicians to be related to zolmitriptan. CONCLUSIONS: The results of this study demonstrate that zolmitriptan tablets 2.5-mg taken for acute migraine attacks are effective and well-tolerated in Korean patients. (J Korean Neurol Assoc 19(1):29~35, 2001
Adult ; Headache ; Humans ; Hyperacusis ; Korea ; Migraine Disorders* ; Outpatients ; Presynaptic Terminals ; Serotonin ; Serotonin Receptor Agonists ; Tablets ; Trigeminal Nuclei