Anoxia ; Brain ; Brain Ischemia ; Cell Death ; Cognition ; Hippocampus ; Ischemia ; Neuregulin-1 ; Neurons ; Neuroprotection ; Neuroprotective Agents

PURPOSE: Hypoxia-mediated neurotoxicity contributes to various neurodegenerative disorders, including Alzheimer disease. Neuregulin-1 (NRG1) plays an important role in the development and plasticity of the brain. The aim of the present study was to investigate the neuroprotective effect and the regulating hypoxic inducible factor of NRG1 in cobalt chloride (CoCl₂) induced hypoxia. METHODS: Hypoxia was induced in SH-SY5Y cells by CoCl₂ treatment. SH-SY5Y cells were pretreated with NRG1 and then treated with CoCl₂. Western blotting, immunocytochemistry, and lactate dehydrogenase (LDH) release assays were performed to examine neuroprotective properties of NRG1 in SH-SY5Y cells. RESULTS: Our data showed that CoCl₂ induced cytotoxicity and changes of hypoxia-inducible factor-1α (HIF-1α) and p53 expression in SH-SY5Y cells. However, pretreatment with NRG1 inhibited CoCl₂-induced accumulation of HIF-1α and p53 stability. In addition, NRG1 significantly attenuated cell death of SH-SY5Y induced by CoCl₂. CONCLUSIONS NRG1 can regulate HIF-1α and p53 to protect neurons against hypoxic damage.

Apoptosis inducing factor (AIF) has been proposed to act as a putative reactive oxygen species scavenger in mitochondria. When apoptotic cell death is triggered, AIF translocates to the nucleus, where it leads to nuclear chromatin condensation and large-scale DNA fragmentation which result in caspase-independent neuronal death. We performed this study to investigate the possibility that, in addition to caspase-dependent neuronal death, AIF induced neuronal death could be a cause of neuronal death in Alzheimer's disease (AD). We have found that AIF immunoreactivity was increased in the hippocampal pyramidal neurons in the Alzheimer brains compared to those of healthy, age-matched control brains. Nuclear AIF immunoreactivity was detected in the apoptotic pyramidal CA1 neurons at the early stage of AD and CA2 at the advanced stage. Nuclear AIF positive neurons were also observed in the amygdala and cholinergic neurons of the basal forebrain (BFCN) from the early stages of AD. The results of this study imply that AIF-induced apoptosis may contribute to neuronal death within the hippocampus, amygdala, and BFCN in early of AD.
Alzheimer Disease ; Amygdala ; Apoptosis ; Apoptosis Inducing Factor ; Brain ; Cell Death ; Cholinergic Neurons ; Chromatin ; DNA Fragmentation ; Hippocampus ; Mitochondria ; Neurons ; Prosencephalon ; Reactive Oxygen Species

The aim of this study was to propose new more reliable peripheral nerve transection model to overcome the defect of the traditional sciatic axotomy model by specifically transecting L5 spinal nerve just after emerging from the intervertebral foramen and confining analysis area to the L5 spinal segment. The adult male Sprague-Dawley rats, weighing 300~350 g at the time of surgery, were used for the experiments. Four different experimental groups were used. 1. Sciatic nerve transection (Sc-Tx) group: transect the sciatic nerve in the popliteal fossa where it divided into the common peroneal nerve and tibial nerve. 2. L5 spinal nerve transection (L5-Tx) group: L5 spinal nerve was specifically transected. 3. Suture (Su) group: L5 spinal nerve was transected and immediately sutured. 4. Control group: the same surgical procedure with L5 spinal nerve transection group was performed except for the excision of L5 spinal nerve. To distinguish L5 motoneurons from the other level ones, the animals were received the retrograde tracer, FluoroGold into the axotomized proximal nerve stump. Serial coronal frozen sections at 40 microm thick through the L4 to L6 spinal segment was performed and the resultant total number of sections was about 180. Approximate serial 50 sections (approximately 2 mm) could be considered as the L5 segment based on the number of the fluorescent signals (above 20). L5 spinal segment could be differentiated from L4 and L6 segment based on their morphological characteristics under Cresyl violet stain. In L5-Tx group, at 2 and 4 weeks post-transection, the number of L5 spinal motoneurons was reduced by 8%. Meanwhile, Sc-Tx and Su groups showed no statistically notable changes. In this study, the authors could propose more reliable peripheral nerve axotomy model than the conventional sciatic nerve axotomy model by specifically transecting L5 spinal nerve and confining the investigating area within the L5 spinal segment.
Adult ; Animals ; Axotomy ; Benzoxazines ; Frozen Sections ; Humans ; Male ; Peripheral Nerve Injuries ; Peripheral Nerves ; Peroneal Nerve ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; Spinal Nerves ; Sutures ; Tibial Nerve ; Viola

The aim of this study was to propose new more reliable peripheral nerve transection model to overcome the defect of the traditional sciatic axotomy model by specifically transecting L5 spinal nerve just after emerging from the intervertebral foramen and confining analysis area to the L5 spinal segment. The adult male Sprague-Dawley rats, weighing 300~350 g at the time of surgery, were used for the experiments. Four different experimental groups were used. 1. Sciatic nerve transection (Sc-Tx) group: transect the sciatic nerve in the popliteal fossa where it divided into the common peroneal nerve and tibial nerve. 2. L5 spinal nerve transection (L5-Tx) group: L5 spinal nerve was specifically transected. 3. Suture (Su) group: L5 spinal nerve was transected and immediately sutured. 4. Control group: the same surgical procedure with L5 spinal nerve transection group was performed except for the excision of L5 spinal nerve. To distinguish L5 motoneurons from the other level ones, the animals were received the retrograde tracer, FluoroGold into the axotomized proximal nerve stump. Serial coronal frozen sections at 40 microm thick through the L4 to L6 spinal segment was performed and the resultant total number of sections was about 180. Approximate serial 50 sections (approximately 2 mm) could be considered as the L5 segment based on the number of the fluorescent signals (above 20). L5 spinal segment could be differentiated from L4 and L6 segment based on their morphological characteristics under Cresyl violet stain. In L5-Tx group, at 2 and 4 weeks post-transection, the number of L5 spinal motoneurons was reduced by 8%. Meanwhile, Sc-Tx and Su groups showed no statistically notable changes. In this study, the authors could propose more reliable peripheral nerve axotomy model than the conventional sciatic nerve axotomy model by specifically transecting L5 spinal nerve and confining the investigating area within the L5 spinal segment.
Adult ; Animals ; Axotomy ; Benzoxazines ; Frozen Sections ; Humans ; Male ; Peripheral Nerve Injuries ; Peripheral Nerves ; Peroneal Nerve ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; Spinal Nerves ; Sutures ; Tibial Nerve ; Viola

PURPOSE: To investigate the effect of dark rearing immediately after birth on the maturation of the visual relay neurons in the lateral geniculate nucleus. METHODS: Fifty neonatal rats were used. Neonates of the control groups were raised under a normal light/dark cycle. Neonates of the experiment groups were dark reared and isolated from light during the entire experimental period, then exposed to the sun light for 1 hour before sacrifice. RESULTS: In the control groups, the neurons in the dorsal lateral geniculate nucleus developed normally at each age tested. In the experiment groups, the cytoplasm of the large neurons in the dorsal lateral geniculate nucleus of 2-week-old rats contained small vesicles, and the cytoplasm of the large neurons of 4-week-old rats was converted into a vacuole-like space. Moreover, c-Fos immunoreactivity of the large neurons in the dorsal lateral geniculate nucleus in the experiment groups was significantly increased compared to that of the control groups. CONCLUSIONS: We suppose that the maturation of the neurons in the lateral geniculate nucleus might be influenced by light stimulation during the critical period. Furthermore, c-Fos could be a marker of the functional activity of the visual relay neurons of the lateral geniculate nucleus in albino rats.
Animals ; Animals, Newborn ; Critical Period (Psychology) ; *Dark Adaptation ; Geniculate Bodies/*metabolism ; Immunohistochemistry ; *Light ; Neurons/*metabolism ; Proto-Oncogene Proteins c-fos/*metabolism ; Rats ; Rats, Sprague-Dawley

Neuregulin-1 (NRG1) plays important roles in the development and plasticity of the brain, and has also been reported to exhibit potent neuroprotective properties. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its role in Alzheimer's disease (AD). AD is characterized by progressive impairment of cognition and behavioral disturbance that strongly correlate with degeneration and death of neurons in the cerebral cortex and limbic brain areas, such as the hippocampus and the amygdala. Here, we show that the ErbB4 and phospho-ErbB4 immunoreactivities were higher intensity in the neurons of the CA1-2 transitional field of AD brains as compared to age-matched controls. Also, ErbB4 expression was increased in the neurons of the cortico medial nucleus amygdala, human basal forebrain and superior frontal gyrus of AD brains. In cerebral cortex and hippocampus of amyloid precursor protein/presenilin 1 double transgenic mice, ErbB4 immunoreactivity significantly increased in comparison to age-matched wild type control. These results suggest that up-regulating of ErbB4 immunoreactivity may involve in the progression of pathology of AD.
Adult ; Alzheimer Disease ; Amygdala ; Amyloid ; Animals ; Brain ; Cerebral Cortex ; Cognition ; Hippocampus ; Humans ; Mice ; Mice, Transgenic ; Neuregulin-1 ; Neurons ; Plastics ; Prosencephalon

In order to present the optimal neuroscience tutorial material for medical students and researchers, this study is aimed to make neuro-digital slide and neuro-atlas based on the histological specimens of human spinal cord and brain stem. Cadavers which had agreed for organ donation for research purpose were used in this study. Brains and spinal cords were extracted within 24 hours after death, and then fixed with 10% neutral buffered formalin. Paraffin blocks were made with the following regions; 8 regions from the spinal cord (the levels of the upper cervical segment, the cervical enlargement, the upper thoracic segment, the mid thoracic segment, the lower thoracic segment, the upper lumbar segment, the lumbar enlargement, the sacral segment), 14 regions from the brain stem (the levels of the spinomedullary junction, the pyramidal decussation, the medial lemniscus decussation, the obex, the mid-olivary medulla, the upper medulla, the pontomedullary junction, the lower pons, the mid pons, the upper pons, the isthmus rhombencephali, the inferior colliculus, the superior colliculus, the posterior commissure). Using virtual microscope software, we made digital neuro-slides which can be used anywhere and anytime regardless of equipment of microscope. To help understanding anatomy and functions of nervous tissue, we also made neuro-atlas based on the digital slide images. As results, the outline and detailed structures of nuclei and tracts are easily discriminated and also matched with marks and nomenclatures of neuro-atlas. Moreover, the cytoarchitecture of each nucleus and histological features can be well distinguished. We hope that this product would be used as a useful neuroscience tutorial material for the medical and paramedical school students, clinical trainees like interns and residents, and also neuroscience researchers.
Brain ; Brain Stem ; Formaldehyde ; Humans ; Inferior Colliculi ; Neurosciences ; Paraffin ; Pons ; Pyramidal Tracts ; Spinal Cord ; Students, Medical ; Superior Colliculi ; Tissue and Organ Procurement

Neuregulin-1 (NRG1) signaling participates in the synaptic plasticity, maintenance or regulation of adult brain. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its localization in Alzheimer's disease (AD) brains. We previously reported that ErbB4 immunoreactivity showed regional difference in the hippocampus of age-matched control. In the present paper, immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology staging were performed in age-matched control (Braak stage 0, n=6) and AD (Braak stage I/V, n=10). Here, we found that ErbB4 immunoreactivity was significantly increased in apoptotic hippocampal pyramidal neurons in the brains of AD patients, compared to those of age-matched control subjects. In AD brains, ErbB4 immunoreactivity was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons. These results suggest that up-regulation of ErbB4 immunoreactivity in apoptotic neuron may involve in the progression of pathology of AD.
Adult ; Alzheimer Disease ; Animals ; Apoptosis ; Brain ; Hippocampus ; Humans ; Neuregulin-1 ; Neurons ; Plastics ; Up-Regulation

During the routine gross anatomical dissection, bilateral absence of the musculocutaneous nerve and unilateral brachioradial artery were found in a 76-year-old Korean male cadaver. At the apex of the axilla, the lateral cord of the brachial plexus united into the median nerve without branching off the musculocutaneous nerve. The flexor arm musculatures, normally innervated by the musculocutaneous nerve, were innervated by two separate branches from the median nerve. The distal one continued as the lateral antebrachial cutaneous nerve. In addition, the radial artery of the left arm was originated from the middle one-third of the brachial artery. At bifurcation, it lay deep to the median nerve and crossed it medially. However, at the elbow, it crossed again the median nerve anterolaterally. Just above the cubital fossa, it anastomosed with the brachial artery. The arterial distribution of the right arm was normal. The separate reports which described the absence of the musculocutaneous nerve or brachioradial artery have been reported. However, this combined variation has not been documented until now.
Aged ; Arm ; Arteries ; Axilla ; Brachial Artery ; Brachial Plexus ; Cadaver ; Elbow ; Humans ; Male ; Median Nerve ; Musculocutaneous Nerve ; Radial Artery