Vardenafil Increases Cell Proliferation in the Dentate Gyrus through Enhancement of Serotonin Expression in the Rat Dorsal Raphe

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.

Immunoreactivity of Somatostatin Receptor Subtype 2 in Dorsal Root Ganglia in the Rat / 대한정형외과학회잡지

PURPOSE: Somatostatin has been suggested to play a role in the transmission of neurotransmitters and in the modulation of pain. Of the different subtypes of somatostatin receptors 2, sstr2A and sstr2B are important in the modulation and transmission of pain. The present study was carried out to investigate sstr2 immunoreactivity in rat. MATERIALS AND METHODS: Dorsal root ganglia (DRG) cells at the L4-L6 levels of the spinal cord of 10 rats (Sprague-Dawley, 200-250 g) were examined for sstr2 by immunohistochemistry. RESULTS: In the control group, sstr2A immunoreactivity was strongly positive in the dense network within laminae I and II of the dorsal horn at spinal levels (L4-L6). In contrast to sstr2A, sstr2B immunoreactivity was observed throughout laminae III-VI. In the DRG, sstr2A and sstr2B immunoreactivities were mainly found in medium-sized neurons. CONCLUSIONS: The distribution of sstr2A immunoreactive cells among sstr2 in the dorsal root ganglia (L4-6) resembles that of somatostatin. Incontrast to sstr2A, sstr2B immunoreactivity showed a different distribution. The presence of sstr2A at laminae I and II, and sstr2B at laminae III-VI of the dorsal horn may modulate sensory functions at these different regions of the spinal cord. Considering different actions according to the receptors of the neurotransmitter, the functions of the isoforms of sstr2 appear variable in terms of modulating and transmitting pain.

Age-Related Changes of Catalase Immunoreactivity in the Main Olfactory Bulbs of Wistar and Spontaneously Hypertensive Rats / 대한해부학회지

The reactive oxygen species (ROS) is well-known for the causative factors inducing ischemia, Parkinson's disease, Alzheimer, amylotrophic lateral sclerosis, hypertension and aging. Catalase (CAT) is an important endogenous antioxidant enzyme against ROS because it removes H2O2 during metabolic processes. Hence, we examined the age-related changes of CAT-immunoreactivity in the main olfactory bulbs (MOB) of the Wistar and spontaneous hypertensive rat (SHR) at various aging stages over 2 years periods; postnatal month 6 (PM 6), PM 12, PM 18 and PM 24. CAT immunoreactive (IR) neurons in Wistar rats were located in the glomerular layer (GL), external plexiform layer (EPL), internal plexiform layer (IPL) and granule cell layer (GCL). The number of CAT-IR neurons slightly decreased agedependently and nearly disappeared at PM 24. At PM 6 and PM 12, the CAT-IR neurons located in the EPL were morphologically identified as granule cells. However, at PM 18 and PM 24, CAT-IR neurons located in the EPL and mitral cell layer (MCL) were morphologically identified as tufted and mitral cells, respectively. CAT-IR neurons in the SHR were located in all layers of the MOB. The number of CAT-IR neurons and CAT immunoreactivity decreased agedependently and nearly disappeared especially in the GL and EPL at PM 24. These findings indicate that the decrease of CAT immunoreactivity may be one of the causative factors for increase of oxidative stress, and these damages may underlie age-related changes in the olfactory process. The early decrease of CAT immunoreactivity in the SHR than in the Wistar rat suggests that the early decreae of CAT may be associated with the cause of hypertensive neuronal damage.

Chronological Alteration of Calbindin D-28k and Calretinin Immunoreactivity in the Gerbil Trigeminal Ganglion After Ischemia-Reperfusion / 대한해부학회지

Many researches have focused upon temporal changes of neurotransmitters and/or neuromodulators in the central nervous system after ischemic insult. In sensory neurons, the spatial and temporal alterations of neurotransmitters have been little studied. Calbindin D-28k (CB) and calretinin (CR) have been suggested to play a role in the transmission of neurotransmitters. Therefore, in the present study we investigated the chronological alteration of CB and CR immunoreactivity in the trigeminal ganglion cells of the Mongolian gerbil after ischemic insult. In the sham operated group, CB and CR immunoreactivities were found in small -, medium -and large -sized neurons. One and two days after ischemia-reperfusion, small and large-sized CB immunoreactive neurons increased significantly. Thereafter, number of the CB immunoreactive neurons decreased markedly. Furthermore, five days after ischemia -reperfusion, CB immunoreactivity was detected in a few neurons, and its immunoreactivity was also very weak in the cytoplasm. Number of the large -sized CR immunoreactive neurons increased significantly one day after ischemia -reperfusion. Thereafter, the number of the large -sized CR immunoreactive neurons decreased. Especially, the number of the medium-sized CR immunoreactive neurons increased dramatically 4 days after ischemia-reperfusion. These results suggest that an increase of CB and CR may play an important role in modulating the mechanoception 1 day after ischemia-reperfusion, because the immunoreactivities increased in large -sized neurons which have the myenlinated A fibers. These results also suggest that significant increase of CR expression in medium -sized neurons 4 and 5 days after ischemia-reperfusion may provoke CR in modulating the nociception or thermoception because the medium-sized neurons which have the myenlinated A sigma or C fibers.

Seizure Induced Alteration of Microtubule Associated Proteins Immunoreactivities in the Mongolian Gerbil Striatum / 대한해부학회지

The present study involves a chronological and comparative analysis of both microtubule-associated protein 1A (MAP1A) and microtubule-associated protein 2 (MAP2) immunoreactivities in the striatum of both seizure resistant (SR) and seizure sensitive (SS) gerbil. The MAP1A immunoreactivity is weakly detected in perikarya of SR gerbils. However, MAP1A immunoreactivity is more accumulated in perikarya and dendrites in the pre-seizure group. At 30 min postictal, MAP1A immunoreactivity in the perikarya is decreased. At 3 hr postictal, MAP1A immunoreactivity in perikarya and dendrites is similarly decreased to the level of SR gerbils. The MAP2 immunoreactivity is weakly detected in the perikarya and dendrites of SR gerbils. However, MAP2 immunoreactivity is more accumulated in perikarya and dendrites. In particular, the neuropil between unstained fiber tracts obviously contains strong MAP2 immunoreactivity. At 30 min postictal, MAP2 immunoreactivity isn't almost observed in striatum. At 3 hr postictal, the MAP2 immunoreactivity is not different in the 30 min post -seizure groups but is only observed in the neuropil. However, at 12 hr postictal, the decrease of both MAP1A and MAP2 immunoreactivities had recovered to the pre -seizure level of SS gerbils. These results suggest that MAPs immunoreactivity in the striatum is different in SR and SS gerbils, and that this difference may be the results of seizure activity in this animal.

The Distribution of CGRP Containing Cells Innervating the Calcaneal Tendon in Rat Dorsal Root Ganglia / 대한해부학회지

This study was performed to investigate origins of the dorsal root ganglion cells containing calcitonin gene -related peptide (CGRP) which innervate the calcaneal tendon in the rat. We used the horseradish peroxidase (HRP) or fluoro -gold (FG) to trace retrogradely somatic afferents in dorsal root ganglion cells after unilateral injections into the rat calcaneal tendon. HRP or fluoro -gold labeled DRG cells for the calcaneal tendon were seen generaaly in lumbosacral (L1 to S1) DRGs ipsilaterally. In lumbosacral DRGs, the largest number of labeled cells were found in the L6 DRG. Many DRG cell bodies contained the CGRP throughout the L1~S1. A plenty of HRP -or FG -labeled cells innervating the calcaneal tendon were also identified to contain the CGRP in L1~S1 DRGs. These FG +/- CGRP DRG cells innervating the calcaneal tendon were primarily found in the L6 DRG. These results suggest that the main sensory DRG for the calcaneal tendon is the L6. This fact may be available in diagnosis and treatment of neurogenic pain in the calcaneal tendon.

Correlation between Tear EGF Concentration and Severity of Dry Eye

PURPOSE: The purpose of this study is to evaluate the difference of tear EGF(epidermal growth factor) concentration between in dry eyes and normal ones, and the relationship between the tear EGF concentration and the severity of corneal epithelial lesion in dry eyes. METHODS: In 43 normal eyes and 52 dry eyes, tear samples were collected with polyester rod(Transob) from the lower fornix after topical anesthesia. EGF concentration was determined by ELISA(enzyme linked immunosorbent assay). Other methods of dry eye examination were also used which include Schir-mer I test, measurement of tear film break up time and fluorescein scoring of corneal epithelial lesion. RESULTS: Tear EGF concentration was significantly lower in dry eyes with corneal epithelial lesion than in normal eyes or dry eyes without corneal epithelial lesion(P<0.05). There was a significant correlation between tear EGF concentration and the severity of corneal epithelial lesion in dry eyes(r=-0.65, P<0.05). In dry eyes with corneal epithelial lesion, tear EGF concentration decreased, which was correlated with the severity of corneal epithelial lesion. CONCLUSIONS: These findings suggest that EGF may be included in the therapeutic armamentarium of dry eyes with corneal erosion.