GABA and 5-HT chitosan nanoparticles decrease striatal neuronal degeneration and motor deficits during liver injury

The metabolic alterations resulted from hepatic injury and cell loss lead to synaptic defects and neurodegeneration that undoubtedly contribute motor deficits. In the present study, GABA and 5-HT chitosan nanoparticles mediated liver cell proliferation influenced by growth factor and cytokines and neuronal survival in corpus striatum of partially hepatectomised rats was evaluated. Liver cell proliferation was initiated and progressed by the combined effect of increased expression of growth factor, insulin like growth factor-1 and decreased expressions of cytokines, tumor necrosis factor-alpha and Akt-1. This was confirmed by the extent of incorporation of thymidine analogue, BrdU, in the DNA of rapidly dividing cells. Inappropriate influx of compounds to corpus striatum resulting from incomplete metabolism elevated GABA(B) and 5-HT2A neurotransmissions compared to those treated with nanoparticles. This directly influenced cyclic AMP response element binding protein, glial cell derived neurotrophic factor and brain derived neurotrophic factor in the corpus striatum that facilitate neurogenesis, neuronal survival, development, differentiation and neuroprotection. Motor deficits due to liver injury followed striatal neuronal damage were scored by grid walk and rotarod studies, which confirmed the regain of motor activity by GABA and 5-HT chitosan nanoparticle treatment. The present study revealed the therapeutic significance of GABA and 5-HT chitosan nanoparticles in liver based diseases and related striatal neuronal damage that influenced by GABA and 5-HT.