Different types of visual cells in the photoreceptor layer of the retinae of the treeshrew (Tupaia belangeri chinensis) as revealed by scanning microscopy.

BACKGROUND: The retinae of treeshrew have never been evaluated by scanning electron microscopic studies. MATERIALS AND METHODS: This work described the visual cells in the photoreceptor layer of the retinae of treeshrew (Tupaia belangeri chinensis) living on the high plateau of Yunnan, China, via scanning electron microscopy. RESULTS: Results indicated five morphologically different types of cones, two of which contain oil droplets in their inner segments. To our knowledge, no prior studies have reported oil droplets in the visual cells of higher mammals, only in lower vertebrate and primitive mammals. In addition, this study revealed one type of degenerative visual cell without outer segments. CONCLUSIONS: The findings signal the needs for additional studies to understand the physiological functions and phylogenetic relationships of the diversity of visual cells in this group of mammal.

Mutated tau, amyloid and neuroinflammation in Alzheimer disease-A brief review.

This review discussed the importance of mutated tau, amyloid and neuroinflammatory factors and microglia in Alzheimer disease. In particular tau, CD4 and TNF alpha were included in the review and the colocalizations of these factors were highlighted. It is important to realize the Alzheimer disease may result from the interactions of these factors. Some of these factors may coexist at the same region and at the same time e.g. mutated tau and amyloid in plaques. A summary scheme of etiology leading to the disease was included.

Long term ketamine and ketamine plus alcohol toxicity - what can we learn from animal models?

This review addressed the adverse effects of the frequently-used recreational drug, ketamine through using mice and monkey models. Our laboratory has documented initially that ketamine can induce the formation of hyperphosphorlated tau (hypertau), which is a hallmark of Alzheimer's disease (AD), in the cerebral cortex of both mice and monkeys as well as apoptosis in neurons in these species. Besides the cerebral cortex, other centers in the central nervous system (CNS) and peripheral nervous system (PNS) are also influenced by ketamine. Cerebellum was found to be down-regulated in both mice and humans after long-term of ketamine administration and it was caused by the apoptosis of Purkinje cells. Deleterious effects in other organs reported in long-term ketamine users include of kidney dysfunction leading to proteinuria, fibrosis of the urinary bladder and reduction in size of the urinary bladder leading to frequent urination, increase of liver fibrosis and cardiac problems such as premature ventricular beats. Moreover, ketamine is usually co-administrated with other chemicals such as caffeine or alcohol. It has been reported increased harmful effects when ketamine was used in combination with the above substances. Mechanisms of damages of ketamine might be due to 1) up-regulation of NMDA receptors leading to overestimation of glutamatergic system or 2) the metabolite of ketamine which was a hydroquinone exerted toxicity.

Extract of white button mushroom affects skin healing and angiogenesis.

White button mushroom extract was examined in this study on (1) its potential effect on angiogenesis in chorioallantoic culture and (2) its recovering effect on the skin after injury in the ICR mice. Methods used included TUNEL assay on apoptosis, immunohistochemistry for vascular endothelial growth factor (VEGF), proliferative cell nuclear antigen (PCNA), epidermal growth factor (EGF), transforming growth factor ß (TGF-ß), and immune factor CD4 and western blotting. The results of chorioallantoic culture showed that the mushroom treatment led to significant increase in densities of VEGF sites. In the skin injury, ICR mice model increased EGF, PCNA, and collagen fibers, along with decrease of TUNEL positive apoptotic cells and limited reaction of TGF-ß and CD4 indicated that white button mushroom extract appeared to have beneficial effects on skin in regeneration and after injury.

Long-term ketamine and ketamine plus alcohol treatments produced damages in liver and kidney.

Ketamine is one of the common recreational drugs used in rave parties and it is frequently taken with alcohol. In spite of this, the potential toxicity of ketamine in liver and kidney has not been fully documented. In this study, ICR mice were treated for periods of 6, 16 and 28 weeks with 30 mg/kg ketamine injected daily intraperitoneally, and together with alcohol (0.5 ml of 10% alcohol for each mouse) during the last 4 weeks of the treatment periods. Our experimental results showed significant damage in liver, including fatty degeneration of liver cells, fibrosis and increase in liver glutamic oxaloacetic transaminase, proliferative cell nuclear antigen and lactate dehydrogenase after 16 weeks of treatment with ketamine. Hydropic degenerations of the kidney tubules were observed as early as 6 weeks of treatment. Long-term ketamine administration (28 weeks) led to atresia of glomeruli in the kidney. Proteinuria was confirmed in the 67% of the ketamine-treated animals after 28 weeks of treatment. It was apparent that ketamine when taken chronically (16 weeks of treatment and thereafter) affected both liver and kidney definitively. The damages in both liver and kidney of these mice were more severe when the animals were treated with both ketamine and alcohol.

Serotonin and its receptors in the human CNS with new findings - a mini review.

Serotonin (5-hydroxytryptamine, 5-HT) is well known to be closely associated with emotional disorders, such as depression and schizophrenia. The seven main members of 5-HT receptor family including the different subtypes are involved in the functional pathways in the brain and their balance in activity helps to maintain the normal mental stability. As any detrimental changes in the 5-HT system is believed to alter emotion in human, different drugs including serotonin reuptake inhibitors (SSRIs) are nowadays commonly used as anti- depressives. In this review, 5-HT(1A) and 5-HT(2A) receptors and serotonergic positive cells in the human were highlighted in particular. It is hoped that this review will give a map of these major 5-HT receptors and serotonergic neurons in the human CNS to facilitate further deciphering of their functions.

How would composite traditional Chinese medicine protect the brain--an example of the composite formula "Pien Tze Huang".

Chinese medicine has a long history of several thousand years. The main form of Traditional Chinese Medicine (TCM) is composite, i.e. a mixture of up to 10 medicinal products. Thus a composite prescription of 4-5 kinds of Chinese medicinal products may contain several hundred kinds of chemical composition. The active ingredients and clinical efficacy of which are difficult to characterize. We aim to review the Chinese literature of TCMs with neuroprotective effects. We illustrate with our study on Pien Tze Huang (PZH) the use of in vivo tests in the study of composite TCM. Our results show evidence that PZH might have neuropreventive effects in rats.

Permanent deficits in brain functions caused by long-term ketamine treatment in mice.

Ketamine, an injectable anesthetic, is also a popular recreational drug used by young adults worldwide. Ketamine is a non-competitive antagonist of N-methyl-d-aspartate receptor, which plays important roles in synaptic plasticity and neuronal learning. Most previous studies have examined the immediate and short-term effects of ketamine, which include learning and cognitive deficits plus impairment of working memory, whereas little is known about the long-term effects of repeated ketamine injections of common or usual recreational doses. Therefore, we aimed to evaluate the deficits in brain functions with behavioral tests, including wire hang, hot plate and water maze tests, plus examine prefrontal cortex apoptotic markers, including Bax, Bcl-2 and caspase-3, in mice treated with 6 months of daily ketamine administration. In our study, following 6 months of ketamine injection, mice showed significant deterioration in neuromuscular strength and nociception 4 hours post-dose, but learning and working memory were not affected nor was there significant apoptosis in the prefrontal cortex. Our research revealed the important clinical finding that long-term ketamine abuse with usual recreational doses can detrimentally affect neuromuscular strength and nociception as part of measurable, stable and persistent deficits in brain function.

TUNEL and growth factor expression in the prefrontal cortex of Alzheimer patients over 80 years old.

To elucidate factors underlying the increased risk of developing Alzheimers disease (AD) in older individuals, the prefrontal cortices of younger (58-79 years) and of older (over 80 years) AD patients were examined by silver impregnation, TUNEL assay and immunohistochemistry for hyperphosphorylated tau, LDH and two growth factors (BDNF, NGF). Quantitative data were compared with those of age-matched controls. TUNEL-positive cells were mainly located in superficial cortical layers of younger and in deeper layers of older AD patients. Their density was more than 5 times higher in older AD than in younger AD (p < or = 0.05), but apoptotic cell morphology was rarely seen. Significantly more neuronal somas were contacted by degenerating fibers both in younger and older AD cortices. Density of tau-immunoreactive cells, which were virtually absent in controls, was twice as high in older AD patients as in younger AD individuals (p < or = 0.05). In younger AD, TUNEL positive cells generally lacked tau immunoreaction, whereas in older AD, most cells were double-labeled for hyperphosphorylated tau and TUNEL (p < or = 0.05). Numerical density of BDNF-immunoreactive cells was significantly reduced by 20 percent in older AD patients, compared to both control individuals and younger AD patients, whereas density of NGF-positive cells was the same in all patient groups examined. The distinct differences between younger and older AD patients suggest a faster progression of AD in older patients.

Silver impregnation of the prefrontal cortices in the brains with long postmortem delay.

Silver impregnation was performed histologically on the prefrontal parts of brains, which had long postmortem delay of one month while under 4 degrees C refrigeration. The brains were from individuals from 60+- to 80+-years old. It was evident from these specimens that, as a whole, the outer layers of the brains degenerated first while the inner layers remained to be silver stainable and had near normal morphology after silver impregnation, even in the oldest specimens. Comparatively, the postmortem degeneration was worse in the outer cortical layers of the older individual when compared with the younger.