Abstract
Cerebral ischemic injuries and neurodegenerative disorders lead to death or impairment of neurons in the central nervous system. Application of stem cell based therapies, namely stimulation of endogenous neurogenesis or cell transplantation, are promising strategies and currently under investigation. Carbon monoxide (CO) is an endogenous product of heme degradation by heme oxygenase. Although there is no published data reporting CO as a factor involved in stem cell differentiation, several evidences support this hypothesis. This gasotransmitter induces mitochondrial biogenesis, which is also broadly described to be involved in metabolic shifts during neuronal differentiation process. Likewise, CO-induced pathways can occur via generation of small amounts of ROS, which are also important signaling molecules in neuronal differentiation. The CO effect on modulation of neuronal differentiation is assessed in three different models with increasing complexity: human neuroblastome SH-S5Y5 cell line, human teratocarcinome NT2 cell line and hippocampal organotypic slice cultures (HOSC). CO does increase the final yield of post-mitotic neurons. During neuronal differentiation, CO promotes an increase on precursor cell proliferation and in parallel CO inhibits cell death. Furthermore, cell mitochondrial population is increased by CORM-A1 supplementation. Further work is needed for assessing the mechanisms underlying CO effects in neuronal differentiation, namely by targeting modulation of cellular metabolic pathways, redox alterations and autophagy related pathways. In conclusion, CO appears as a promising therapeutic molecule to stimulate endogenous neurogenesis or to improve in vitro neuronal production for cell therapy strategies.
Highlights
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia
The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression
No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression
Summary
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors
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