BACKGROUND: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to α-tocopherol. It has been reported that α-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs). METHODS: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol (0–50 µM) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion. RESULTS: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP. CONCLUSION: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.
Acid Phosphatase ; Antioxidants ; Bone Resorption ; Cell Fusion ; Dentin ; Gene Expression ; Macrophage Colony-Stimulating Factor ; Macrophages ; Molecular Structure ; Osteoclasts ; p38 Mitogen-Activated Protein Kinases ; Propofol ; RANK Ligand ; RNA, Messenger

Melatonin affects diverse physiological functions through its receptor and plays an important role in the central nervous system. In the present study, we compared immunoreactivity patterns of arylalkylamine N-acetyltransferase (AANAT), an enzyme essential for melatonin synthesis, and melatonin receptor type 1B (MT2) in the spinal cord of young adult (2~3 years) and aged (10~12 years) beagle dogs using immunohistochemistry and Western blotting. AANAT-specific immunoreactivity was observed in the nuclei of spinal neurons, and was significantly increased in aged dog spinal neurons compared to young adult spinal neurons. MT2-specific immunoreactivity was found in the cytoplasm of spinal neurons, and was predominantly increased in the margin of the neuron cytoplasm in aged spinal cord compared to that in the young adult dogs. These increased levels of AANAT and MT2 immunoreactivity in aged spinal cord might be a feature of normal aging and associated with a feedback mechanism that compensates for decreased production of melatonin during aging.
Age Factors ; Aging/physiology ; Animals ; Arylalkylamine N-Acetyltransferase/*analysis/immunology/physiology ; Blotting, Western ; Dogs ; Fluorescent Antibody Technique ; Male ; Receptor, Melatonin, MT2/*analysis/immunology/physiology ; Spinal Cord/*chemistry/immunology/physiology

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.
Animals ; Artifacts ; Basal Ganglia ; Deep Brain Stimulation ; Dopamine ; Electric Stimulation ; Globus Pallidus ; Neurons ; Parkinson Disease ; Rats ; Subthalamic Nucleus

Alpha-synuclein (alpha-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of alpha-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that alpha-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that alpha-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging.
Adult ; Aged ; Aging ; alpha-Synuclein ; Animals ; Dogs ; Glial Fibrillary Acidic Protein ; Gliosis ; Humans ; Mammals ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease ; Peripheral Nervous System ; Spinal Cord ; Young Adult

In this study, we characterize the hemodynamic changes in the main olfactory bulb of anesthetized Sprague-Dawley (SD) rats with near-infrared spectroscopy (NIRS, ISS Imagent) during presentation of two different odorants. Odorants were presented for 10 seconds with clean air via an automatic odor stimulator. Odorants are: (i) plain air as a reference (Blank), (ii) 2-Heptanone (HEP), (iii) Isopropylbenzene (IB). Our results indicated that a plain air did not cause any change in the concentrations of oxygenated (Delta[HbO2]) and deoxygenated hemoglobin (Delta[Hbr]), but HEP and IB induced strong changes. Furthermore, these odor-specific changes had regional differences within the MOB. Our results suggest that NIRS technology might be a useful tool to identify of various odorants in a non-invasive manner using animals which has a superb olfactory system.
Animals ; Benzene Derivatives ; Hemodynamics ; Hemoglobins ; Ketones ; Odors ; Olfactory Bulb ; Oxygen ; Rats ; Spectroscopy, Near-Infrared

Neurogenesis in the adult brain occurs continuously throughout life. The main olfactory bulb (MOB) is the first central relay of the olfactory system. We examined proliferation of newly generated cells in each layer of the gerbil MOB after 5 min of transient cerebral ischemia using doublecortin (DCX), a marker of neuronal progenitors. Many DCX immunoreactive neuroblasts were found in the all layers of the MOBs of control and ischemia groups. Ten to 15 days after ischemia/reperfusion, no difference in numbers of DCX immunoreactive neuroblasts was found in the MOB. Thirty days after ischemia/reperfusion, significant increase of DCX immunoreactive cells was observed in all layers of ischemic MOB. This result indicates that neuroblasts increase in the MOB from 30 days after transient cerebral ischemia in gerbils.
Adult ; Brain ; Gerbillinae ; Humans ; Ischemia ; Ischemic Attack, Transient ; Neurogenesis ; Neurons ; Olfactory Bulb

A brain-machine interface (BMI) has recently been introduced to research a reliable control of machine from the brain information processing through single neural spikes in motor brain areas for paralyzed individuals. Small, wireless, and implantable BMI system should be developed to decode movement information for classifications of neural activities in the brain. In this paper, we have developed a totally implantable wireless neural signal transmission system (TiWiNets) combined with advanced digital signal processing capable of implementing a high performance BMI system. It consisted of a preamplifier with only 2 operational amplifiers (op-amps) for each channel, wireless bluetooth module (BM), a Labview-based monitor program, and 16 bit-RISC microcontroller. Digital finite impulse response (FIR) band-pass filter based on windowed sinc method was designed to transmit neural signals corresponding to the frequency range of 400 Hz to 1.5 kHz via wireless BM, measuring over -48 dB attenuated in the other frequencies. Less than +/-2% error by inputting a sine wave at pass-band frequencies for FIR algorithm test was obtained between simulated and measured FIR results. Because of the powerful digital FIR design, the total dimension could be dramatically reduced to 23x27x4 mm including wireless BM except for battery. The power isolation was built to avoid the effect of radio-frequency interference on the system as well as to protect brain cells from system damage due to excessive power dissipation or external electric leakage. In vivo performance was evaluated in terms of long-term stability and FIR algorithm for 4 months after implantation. Four TiWiNets were implanted into experimental animals' brains, and single neural signals were recorded and analyzed in real time successfully except for one due to silicon- coated problem. They could control remote target machine by classify neural spike trains based on decoding technology. Thus, we concluded that our study could fulfill in vivo needs to study various single neuron-movement relationships in diverse fields of BMI.
Automatic Data Processing ; Brain ; Brain-Computer Interfaces ; Neural Prostheses ; Organothiophosphorus Compounds ; Signal Processing, Computer-Assisted ; Silanes

The aim of this study is to verify the feasibility of control of one-dimensional (1-D) rotating machine using neural activities of Prefrontal cortex (PFC) in a BCI system. In this study, adult male Sprague-Dawley rats received bilateral implantation of recording micro-electrodes in PFC area. The spontaneous activities of a pair of PFC neurons of water-deprived rats were encoded and converted through a triple-step threshold comparator algorithm to three commands for one-dimensional movement control of a robotic wheel for accessing water. Averaged activities of two PFC neurons were quantized in every 200 ms to four ranges of activities around the mean firing rates (+/-0.5 SD) and were converted to four values. After comparison of the values of two chosen neuron units, direction and speed of rotation were decided. Rats were trained to complete one-dimensional control task to obtain water reward. The results indicated the percentage of stop event increased alone with more training. Different brain activity significantly influenced total water-drinking duration and non-water-drinking duration. Events generated from neuronal activity differed according to variant experimental sessions. Correlation between two signal units impacted controlling performance. Overall, the results of this study suggest that rats were able to manipulate the 1-D BCI system by differentially modulating PFC single neuron activities according to different circumstances.
Adult ; Animals ; Brain ; Brain-Computer Interfaces ; Fires ; Humans ; Male ; Neurons ; Prefrontal Cortex ; Rats ; Rats, Sprague-Dawley ; Reward ; Water

Choi JH et al. Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus; Correlation with Memory Impairment. Korean J Anat (2009) 42(1): 41-48. Please note that there is error in the above article:On page 47 (ACKNOWLEDGEMENTS) on lines 39-40 in the right column, "(MOEHRD) (KRF-2007-8R07- 0301-064-S000100)" should be "(MOEHRD, Basic Research Promotion Fund) (KRF-2007-412-J00502)"

The distributions of calretinin (CR)- and parvalbumin (PV)-immunoreactive neurons in the main olfactory bulb (MOB) of the goat were examined in this study. As in other animals, the goat MOB has a characteristic laminar structure with laminar types and distribution patterns in each layer. CR-immunoreaction was observed in all layers of the MOB, except for the olfactory nerve layer. Most of CR-immunoreactive neurons were observed in the glomerular and granule cell layers. Relatively small number of CR-immunoreactive neurons was detected in other layers. These CR-immunoreactive neurons were interneurons. PV-immunoreaction was detected in all layers. In contrast to CR, olfactory nerve bundles were immunostained with PV. Most of PV-immunoreactive neurons were distributed in the glomerular and granule cell layers. PV-immunoreactive neurons were interneurons. This result suggests that CR and PV may play important roles in the olfactory signal modulation through interneurons in the goat MOB.
Animals ; Calcium-Binding Protein, Vitamin D-Dependent ; Calcium-Binding Proteins ; Goats ; Immunohistochemistry ; Interneurons ; Neurons ; Olfactory Bulb ; Olfactory Nerve ; Smell