Abstract
The effects of cholinergic insult were studied in the hippocampal formation of cholinergic lesioned rats at metabolic and cellular levels by in vivo nuclear magnetic resonance spectrometry and immuno-histochemical approaches. Cholinergic deafferentation was induced by injection of the cholinergic immunotoxin 192 IgG-saporin into the medial septum. The immunotoxin effects were tested at 3, 7, and 30 days post-lesion. Rats with cholinergic deafferentation of the hippocampus showed a lack of NeuN immunoreactivity cells, indicating neuronal loss in hippocampal formation. This neuronal loss was more pronounced in the dentate gyrus, underlining the greater sensitivity of this region to the cholinergic insult. Interestingly, this neuronal loss was not associated with metabolic alteration. These data suggest that the remaining neurons upregulated their functional activity, which would contribute to maintaining the relatively stable level of metabolites and memory abilities. No alteration in GFAP and OX42 immunostaining and in glutamine and myoionositol metabolite concentration was observed in the deafferented regions.
Highlights
Epigenetic alterations play important roles in a wide variety of physiological and pathological events [1]
The inner and outer segments of photoreceptor cells were difficult to discern. These eye defects were even observed in embryos as early as E12.5, so they believe that SIRT1 have an important role in eye morphogenesis and retinal development [22]
By performing in situ hybridization with radioactive probes, SIRT1 mRNA was detected in the Outer Nuclear Layer (ONL), Inner Nuclear Layer (INL), and Ganglion Cell Layer (GCL) of the retina
Summary
Epigenetic alterations play important roles in a wide variety of physiological and pathological events [1]. The human sirtuins family, homologs of the yeast silent information regulator 2(Sir2), belongs to class III HDACs. They are NAD+-dependent deacetylases and contain seven members (SIRT1-7) with varied functions, structures, and localizations [5]. From the finding an ability to maintain chromatin silencing and genome stability [17], SIRT1 has been linked to variety of physiological and pathological processes and diseases such as DNA repair, cell fate, metabolic regulation, apoptosis, cell survival, aging, inflammation, angiogenesis, oxidative stress, neurodegenerative diseases, cancer and cardiovascular dysfunction.
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