BACKGROUND AND OBJECTIVES: It is well-established that neurogenesis continues to occur during life in the restricted brain areas, such as the glomerular and granule cell layers of the olfactory bulb. Doublecortin is a protein required for neuronal migration in the developing brian and olfactrory bulb, and is expressed in postmitotic migrating and differentiating neurons during embryonic and postnatal development periods. We investigated age-related changes of doublecortin positive cells in the olfactory bulb of aged rat compared with new born rat. MATERIALS AND METHOD: Four months old (control group, n=7) and 24 months old (aged group, n=7) male Fischer 344 rats were used in this study. Olfactory bulbs of the rats were cut into 40 micro m-thick coronal sections and immunostained. We counted the doublecortin positive cells and neurofibrils, and measured the optical density of doublecortin by layer. We compared the results between the aged group and the control group. RESULTS: In the olfactory bulbs of aged group, we observed less doublecortin positive cells, neurofibrils and lower optical density than the control group. Doublecortin is expressed during life in migratory neuroblasts of the olfactory bulb of the rats. This expression is reduced in the aged group and the reduced degree is variable according to the layer. CONCLUSION: Age-related changes of the olfactory bulb are associated with the reduction of postnatal neurogenesis, especially during the migration and differentiaion stages. This changes result in reduction of interneurons of the olfactory bulb, and may be responsible for the decreased olfactory function.
Aging ; Animals ; Brain ; Child, Preschool ; Humans ; Interneurons ; Male ; Neurofibrils ; Neurogenesis ; Neurons ; Olfactory Bulb* ; Rats*

The purpose of this study was to determine the effect of treatment with thyrotropin releasing hormone(TRH) on the somatosensory evoked potentials(SSEPs) and ultrastructures of myelinated nerve fibers in injured spinal cords. Spinal cords of cats were injured expermentally at the second lumbar vertebra level with 20gm-20cm(400gm-cm) impact force using modified Allen's weight drop method. The animals were treated with TRH(2mg/Kg, bolus, then 2mg/Kg/hour, IV, for 4 hours) 1 hour after injury. SSEPs were checked serially in both treated and untreated groups for 24 hours. And the fine strucures of myelinated nerve fibers in the white matters were observed in electronmicroscope before and after the injury in both groups. In treated groups, the inital positive waves were re-elicited 3 hours after injury which was eliminated immediately after injury. Fine structure of the myelinated nerve fibers were changed progressively. With time after injury, the myelinated nerve fibers showed enlarged periaxonal spaces, irregulary contoured axons, and disarray of myelin sheaths. By 4 hours after injury, there appeared marked separation and disrray of myelin sheaths, and mitochondria and neurofibrils in axoplasm showed serve degeneration. The result of this study suggested that TRH has a beneficial effect on the re-elicitation of SSEP's and the preservation of myelinated nerve fibers in the acute stage of spinal cord injury.
Animals ; Axons ; Cats ; Evoked Potentials, Somatosensory* ; Mitochondria ; Myelin Sheath* ; Nerve Fibers, Myelinated* ; Neurofibrils ; Spinal Cord Injuries ; Spinal Cord* ; Spine ; Thyrotropin* ; Thyrotropin-Releasing Hormone*

Alzheimer's disease (AD) is a common disease in elder people. Its incidence rate is about 5% in people above 60 years old. It has become an important factor that seriously impacts the development of families and society, and caused wildly attention all over the world. In this article, we discuss the mechanisms of AD in four aspects and put forward the strategies of drug therapy.
Aged ; Alzheimer Disease ; drug therapy ; etiology ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; metabolism ; Apoptosis ; drug effects ; Cholinesterase Inhibitors ; therapeutic use ; Female ; Humans ; Male ; Nerve Growth Factor ; metabolism ; Neurofibrils ; pathology ; Nootropic Agents ; therapeutic use ; Plaque, Amyloid ; metabolism ; Synapses ; pathology

Alzheimer's disease, the most common cause of dementia, is characterized by two major pathological hallmarks: amyloid plaques and neurofibrillary tangles. Based on these two indicators, an amyloid cascade hypothesis was proposed, and accordingly, most current therapeutic approaches are now focused on the removal of beta-amyloid peptides (Abeta from the brain. Additionally, strategies for blocking tau hyperphosphorylation and aggregation have been suggested, including the development of drugs that can block the formation of tangles. However, there are no true disease-modifying drugs in the current market, though many drugs based on theories other than Abeta and tau pathology are under development. The purpose of this review was to provide information on the current development of AD drugs and to discuss the issues related to drug development.
Alzheimer Disease ; Amyloid ; Brain ; Dementia ; Neurofibrillary Tangles ; Peptides ; Plaque, Amyloid

Alzheimer's disease(AD) is a progressive dementia characterized by global cognitive decline and is defined pathologically by amyloid plaques and neurofibrillary tangles. In the past 10 years, important progress has been made in the understanding of the pathogenic mechanism of AD, and new therapeutic targets have become available that should allow the underlying disease process to be tackled directly. In this respect, the 'amyloid hypothesis' has been become the dominant theory in the cause of AD. New strategies for conquering the AD include attempts to stop the production of beta-amyloid protein(Abeta), increasing Abeta clearance, or interfere with Abeta aggregation and precipitation into fibril or plaques. This review summarizes recent advances in research on AD and inspects the perspective of research in potential therapies of AD.
Aged ; Alzheimer Disease* ; Amyloid ; Dementia ; Humans ; Neurofibrillary Tangles ; Plaque, Amyloid

The pathophysiologic process of Alzheimer's disease (AD) begins years before the diagnosis of clinical dementia. This concept of preclinical AD has arisen from the observation of AD pathologic findings such as senile plaques and neurofibrillary tangles in the brains of people who at the time of death had normal cognitive function. Recent advances in biomarker studies now provide the ability to detect the pathologic changes of AD, which are antecedent to symptoms of the illness, in cognitively normal individuals. Functional and structural brain alterations that begin with amyloid-beta accumulation already show the patterns of abnormality seen in individuals with dementia due to AD. The presence of preclinical AD provides a critical opportunity for potential interventions with disease-modifying therapy. This review focuses on the studies of antecedent biomarkers for preclinical AD.
Aging ; Alzheimer Disease ; Biomarkers ; Brain ; Dementia ; Neurofibrillary Tangles ; Plaque, Amyloid

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model .
Alzheimer Disease ; Amyloid beta-Peptides ; Humans ; Neurofibrillary Tangles ; tau Proteins

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.
Alzheimer Disease ; Amyloid beta-Peptides ; Humans ; Neurofibrillary Tangles ; tau Proteins

BACKGROUND: Alzheimer's disease (AD) is characterized by the pathology of amyloid plaques and tau-associated neurofibrillary tangles. Acetylcholine esterase (AChE) transforms the beta-amyloid monomer into an oligomer, and increases beta-amyloid aggregation in the brain. Increased beta-amyloid breaks the cytoskeleton of the brain by hyperphosphorylation of the tau protein. Previous studies support that AChE inhibitor has an inhibitory effect on toxicity of the beta-amyloid and phophorylated tau protein. The purpose of this study was to analyze the CSF beta-amyloid 1-42 (A beta 1-42) and phosphorylated tau protein in AD and determine their difference depending on whether AChE inhibitor was taken or not. METHODS: Subjects included 16 AD, 14 normal controls, and 15 disease controls. Nine of AD group had taken an AChE inhibitor while the remainder had not. The CSF A beta 1-42 and phosphorylated tau were measured by ELISA. RESULTS: The CSF A beta 1-42 levels were lower in AD patients than in other groups (p<0.01). We also found increased CSF A beta 1-42 levels in the AChE inhibitor users, compared with non-users. CONCLUSIONS: The level of CSF A beta 1-42 may have a diagnostic value in the patients with cognitive impairments. Also, we may expect the effect of AChE inhibitor on Alzheimer's pathology by measuring CSF A beta 1-42 levels. Therefore, the level of CSF A beta 1-42 may serve as a biological surrogate marker for AD treatment.
Acetylcholine ; Alzheimer Disease ; Biomarkers ; Brain ; Cytoskeleton ; Humans ; Neurofibrillary Tangles ; Plaque, Amyloid ; tau Proteins

A patient presenting with the characteristic clinical features of the dementia of Pick's type is described, in whom neuropathological examination of brain biopsy material revealed atypical features, including extensive subcotical gliosis with mild cortical neuronal loss and without any neuronal cytoskeletal inclusions (Pick bodies, neurofibrillary tangles, and Lewy bodies) and amyloid deposits (senile plaques). And she has the suggestive family history of the same clinical features in her two brothers. So, the clinical and pathological features are discussed with particular reference to typical Alzheimer's disease and Pick's disease, and it is proposed that the case should be classified as familial progressive subcortical gliosis.
Alzheimer Disease ; Biopsy ; Brain ; Dementia ; Gliosis* ; Humans ; Neurofibrillary Tangles ; Neurons ; Pick Disease of the Brain ; Plaque, Amyloid ; Siblings