Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New strategies have recently been developed where infusion of neurotrophic factors into the brain can rescue different populations of neurons. Infusion of nerve growth factor (NGF) has been used in combination with transplants of chromaffin tissue to the striatum in the rat model of Parkinson's disease as well as to patients suffering from Alzheimer's disease. In this study we have evaluated the distribution of recombinant human NGF (rhNGF) in different brain areas and evaluated morphological and electrophysiological effects after continuous infusion for 2 weeks of rhNGF (500 micrograms/ml) into the striatum of normal rats. One week after termination of rhNGF infusion, NGF levels in the infused striata were 10-fold increased while in contralateral striata normal levels were found. Extracellular recordings from striatal neurons revealed a significantly decreased spontaneous firing rate (0.76 +/- 0.07 Hz) in rats infused with rhNGF compared to vehicle-infused control animals (1.36 +/- 0.16 Hz). Local application of rhNGF during recordings showed no direct inhibitory effect of NGF on neuronal discharge rate. Immunohistochemistry, using antibodies against acetyl cholinesterase (AChE) and glial fibrillary acidic protein (GFAP), revealed a 38.7 +/- 7.0% increase in optical density of AChE immunoreactivity close to the NGF source and an increase in GFAP-positive profiles that was restricted close to the implanted dialysis fibre. In situ hybridization showed an increase in mRNAs for choline acetyltransferase, trkA, p75 and muscarinic m2 receptor in the large neurons of rhNGF-infused striatum. Messenger RNAs for m1 and m4 receptors in striatal neurons were not changed. Thus, chronic infusion of rhNGF into the striatum caused a cholinergic hyperinnervation and reduced spontaneous activity of striatal neurons.
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PMID:Chronic infusion of nerve growth factor into rat striatum increases cholinergic markers and inhibits striatal neuronal discharge rate. 892 Dec 73

The periodontal ligament has a rich sensory nerve supply which serves as a sensory apparatus in addition to tooth support. The periodontal ligament contains nociceptors and low-threshold mechanoreceptors. Stimuli applied to teeth evoke various oral reflexes, which make smooth mastication possible via the periodontal mechanoreceptors. Recent morphological and physiological studies have revealed that Ruffini endings, categorized as low-threshold slowly adapting type II (SA II), are essential mechanoreceptors in the periodontal ligament. The periodontal Ruffini endings are ultrastructurally characterized by expanded axon terminals filled with a number of mitochondria and terminal or lamellar Schwann cells. The axon terminals of the periodontal Ruffini endings have finger-like projections, i.e. axonal spines, extending into the surrounding tissue to detect the deformation of collagen fibers. As histochemical marker enzymes for the periodontal Ruffini endings, the axon terminals and terminal Schwann cells are reactive for cytochrome oxidase activity and both acid phosphatase activity and non-specific cholinesterase activity, respectively. Many experimental studies also have revealed that periodontal Ruffini endings have high potential for neuroplasticity, confirmed by intense immunoreactivity for p75-NGFR and GAP-43. Mechanical stimuli due to tooth eruption and occlusion might be a prerequisite for the differentiation and maturation of the periodontal Ruffini endings. Further investigations are needed for clarifying the involvement of growth factors and the molecular mechanism of the development and regeneration processes of the Ruffini endings.
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PMID:[Morphological basis on periodontal Ruffini endings]. 961 78

The periodontal ligament receives a rich sensory nerve supply and contains many nociceptors and mechanoreceptors. Although its various kinds of mechanoreceptors have been reported in the past, only recently have studies revealed that the Ruffini endings--categorized as low-threshold, slowly adapting, type II mechanoreceptors--are the primary mechanoreceptors in the periodontal ligament. The periodontal Ruffini endings display dendritic ramifications with expanded terminal buttons and, furthermore, are ultrastructurally characterized by expanded axon terminals filled with many mitochondria and by an association with terminal or lamellar Schwann cells. The axon terminals of the periodontal Ruffini endings have finger-like projections called axonal spines or microspikes, which extend into the surrounding tissue to detect the deformation of collagen fibers. The functional basis of the periodontal Ruffini endings has been analyzed by histochemical techniques. Histochemically, the axon terminals are reactive for cytochrome oxidase activity, and the terminal Schwann cells have both non-specific cholinesterase and acid phosphatase activity. On the other hand, many investigations have suggested that the Ruffini endings have a high potential for neuroplasticity. For example, immunoreactivity for p75-NGFR (low-affinity nerve growth factor receptor) and GAP-43 (growth-associated protein-43), both of which play important roles in nerve regeneration/development processes, have been reported in the periodontal Ruffini endings, even in adult animals (though these proteins are usually repressed or down-regulated in mature neurons). Furthermore, in experimental studies on nerve injury to the inferior alveolar nerve, the degeneration of Ruffini endings takes place immediately after nerve injury, with regeneration beginning from 3 to 5 days later, and the distribution and terminal morphology returning to almost normal at around 14 days. During regeneration, some regenerating Ruffini endings expressed neuropeptide Y, which is rarely observed in normal animals. On the other hand, the periodontal Ruffini endings show stage-specific configurations which are closely related to tooth eruption and the addition of occlusal forces to the tooth during postnatal development, suggesting that mechanical stimuli due to tooth eruption and occlusion are a prerequisite for the differentiation and maturation of the periodontal Ruffini endings. Further investigations are needed to clarify the involvement of growth factors in the molecular mechanisms of the development and regeneration processes of the Ruffini endings.
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PMID:The Ruffini ending as the primary mechanoreceptor in the periodontal ligament: its morphology, cytochemical features, regeneration, and development. 1075 11

Neurotrophin-4/5 (NT-4/5) - a member of the neurotrophic factors - is a ligand for TrkB, which has been reported to be expressed in the mechanoreceptive Ruffini endings of the periodontal ligament. The present study examined developmental changes in the terminal morphology and neural density in homozygous mice with a targeted disruption of the nt-4/5 gene and wild-type mice by immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal marker, and by quantitative analysis using an image analyzer. Postnatal development of terminal Schwann cells was also investigated by enzymatic histochemistry for non-specific cholinesterase activity (ChE). Furthermore, the immuno-expression of TrkB and low affinity nerve growth factor receptor (p75-NGFR) was surveyed in the periodontal Ruffini endings as well as trigeminal ganglion. At postnatal 1 week, the lingual periodontal ligament of both types of mice contained PGP 9.5-positive nerve fibers showing a tree-like ramification with axonal swellings in their course. In both types of mice at 2 weeks of age, comparatively thick nerve fibers with a smooth outline increased in number, and frequently ramified to form nerve terminals with dendritic profiles. However, no typical Ruffini endings with irregular outlines observed in the adult wild-type mice were found in the periodontal ligament at this stage. At postnatal 3 weeks, typical Ruffini endings with irregular outlines were discernable in the periodontal ligament of the wild-type mice while the dendritic endings showing smooth outlines were restricted to the homozygous mice. After postnatal 8 weeks, both types of mice showed an increase in the number of Ruffini endings, but the morphology differed between the wild-type and NT-4/5 homozygous mice. In the wild-type mice, a major population of the Ruffini endings expanded their axonal branches and developed many microprojections, resulting in a reduction of endings with smooth outlines. In contrast, we failed to find such typical Ruffini endings in the periodontal ligament of the homozygous mice: A majority of the periodontal Ruffini endings continued to show smooth outlines at postnatal 12 weeks. Quantitative analysis on neural density demonstrated a reduction in the homozygous mice with a significant difference by postnatal 8 weeks. Enzymatic histochemistry for non-specific ChE did not exhibit a distinct difference in the distribution and density of terminal Schwann cells between wild-type and homozygous mice. Furthermore, TrkB and p75-NGFR mRNA and proteins did not differ in the trigeminal ganglion between the two types. The periodontal Ruffini endings also displayed immunoreactivities for TrkB and p75- NGFR in both phenotypes. These findings suggest that the nt-4/5 gene depletion caused a delay in the formation and maturation of the periodontal Ruffini endings in the mice by inhibiting the growth of the periodontal nerves at an early stage, and indicate that multiple neurotrophins such as NT- 4/5 and BDNF might play roles in the development and/or maturation of the periodontal Ruffini endings.
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PMID:Neurotrophin-4/5-depletion induces a delay in maturation of the periodontal Ruffini endings in mice. 1647 47

This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.
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PMID:Alleviating effects of Bushen-Yizhi formula on ibotenic acid-induced cholinergic impairments in rat. 2548 64