Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica (Linn) During Growth Spurt Period in Rats

Centella asiatica (CeA) is a creeping herb, growing in moist places in India and other Asian Countries. Ayurvedic system of medicine, an alternate system of medicine in India, uses leaves of CeA for memory enhancement. Here, we have investigated the role of CeA fresh leaf juice treatment during growth spurt period of rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. The present study was conducted on neonatal rat pups. The rat pups (7-days-old) were fed with 2, 4 and 6 ml/kg body of fresh leaf juice of CeA for 2, 4 and 6 weeks. After the treatment period, the rats were killed, brains removed and amygdaloid neurons impregnated with Silver nitrate (Golgi staining). Amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure dendritic length) quantified. These data were compared with those of age-matched control rats. The results showed a significant increase in dendritic length (intersections) and dendritic branching points along the length of dendrites of the amygdaloid neurons of rats treated with 4 and 6 ml/kg body weight/day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that constituents/active principles present in CeA fresh leaf juice has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders

Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: behavioral and ultrastructural approaches

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats. Materials and methods: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl’s staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes. Results: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil. Conclusion: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA

Asiatic Acid Inhibits Liver Fibrosis by Blocking TGF-beta/Smad Signaling In Vivo and In Vitro

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl4) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury

Partialk-trees: Algorithms and applications

Partial k-trees are a recursively defined class of graphs that allow efficient algorithms for a variety of combinatorial optimization problems. An O(n\sp2) algorithm for the Bisection Width problem on partial k-trees is presented. The O(n\sp2) Bi-section width algorithm forms the basis for a polynomial time grid embedding for partial k-trees. The embedding is provably good, in the sense that the resulting layout is no more than O(A log\sp4 N) where A is the optimal layout for any N node, degree 4, partial k-tree. A Theory of Structure Preserving Expansions is presented and characterized. The machinery for successively deriving partial k-trees, as a hierarchy of graphs of bounded complexity has been developed. The graphs at each level are derived by expanding the parent graphs at the previous level. The expansion process is Structure Preserving, in the sense that each expanded graph is a partial k\sp\prime-tree for some k\sp\prime. The expansion of planar partial k trees is considered in detail and bounds on k\sp\prime are developed for the important case of expanding tree subgraphs of the parent graphs. A linear time algorithm for the Steiner tree problem on partial k-trees is presented. This is also the largest class of graphs for which a polynomial time Steiner tree algorithm is currently known. The framework of structure preserving expansions and the linear time algorithm for the Steiner tree problem have been applied to the physical design of VLSI circuits. An optimal algorithm for hierarchical floorplanning and Global Routing has been developed. The hierarchical floorplanning algorithm developed in this thesis, allows expansion of modules to any fixed k modules at a lower level, without placing any restrictions on the geometry of the placement

Loss of NRF2 results in decreased neuronal arborization and synaptic density and causes exacerbated age-related cognitive impairment.

Background: As the brain ages, free radicals accumulate and cause damage to cellular macromolecules. This increased oxidative damage is thought to contribute to the cognitive decline observed in aging. Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) has been shown to improve neuronal health in aging and neurodegenerative diseases. Yet exactly how NRF2 participates in maintaining synaptic and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects synaptic density and cognitive performance in aged mice. Methods: Dendritic arborization and synaptic was evaluated in hippocampal neurons isolated from mice lacking NRF2 (NRF2KO) and from wild-type (WT) C57BL6 mice. Mitochondrial function of these neurons was evaluated using the Seahorse XF platform. Hippocampal and cortical expression of synaptic genes were measured. Results: NRF2KO neurons had significantly reduced dendritic complexity relative to WT neurons as well as reduced synaptic gene expression. Similar deficits in synaptic gene expression were observed in the brains of aged NRF2KO mice relative to WT mice. Conclusions: These data point to a role for NRF2 in maintaining synaptic health and cognitive function during aging and suggest that the transcription factor may be a viable target for cognitive enhancing interventions. Because increased oxidative stress and cognitive impairment also occur together in many neurodegenerative conditions the therapeutic potential of NRF2 activating agents may extend beyond healthy aging

Microprocessor-based polynomial generator

A new method of generating polynomials using microprocessors is proposed. The polynomial is generated as a 16-bit digital word. The algorithm for generating a variety of basic 'building block' functions and its implementation is discussed. A technique for generating a generalized polynomial based on the proposed algorithm is indicated. The performance of the proposed generator is evaluated using a commercially available microprocessor kit