Neuroprotective Effects of N-Acetyl-Methoxytryptamine in a Neurotoxic Mice Model of Huntington’s Disease Induced by Quinolinic Acid

Authors: Avilés-Reyes RX*, Palacios P and Vega M

DOI: 10.23880/nnoaj-16000138

Volume 4, Issue 2

Abstract

Huntington’s Disease (HD) is an autosomal dominant neuropathology associated with severe degeneration in neurons of the basal ganglia. It is characterized by progressive motors symptoms, cognitive deficits and dementia. The genetic mutation induces trinucleotide repeat expansion (TNR) of cytosine, adenine and guanine (CAG). The CAG-repeat is translated into a poly glutamine (polyQ) stretch caused by molding of DNA “loop out” structures and DNA slippage during the replication. This expanded sequence encodes a mutant huntingtin (mHtt), which is associated to neuronal dysfunction, cellular death, ubiquitous molecular and cellular anomalies. Furthermore, there are progressive impairments in motor control, cognitive function and mood. Quinolinic acid (QA) is an excitotoxic compound in humans and animals that has been linked to HD. N-acetyl-methoxytryptamine (MLT) is a hormone that produce anti-oxidant and anti-inflammatory effects on cell damage. The principal aim of this study is to know if QA induces damage in striatal astrocytes and neurons and to evidence how MLT can participate as a neuroprotectant agent against the neurotoxic injury. We inoculate QA intrastriatal in 8 weeks old wild type (WT) female mice as endogenous neurotoxic model of HD. Here, we worked with three different groups of mice, and the striatal injection was administrated in all animals. PBS were inoculated in control mice; the second group was injected only QA; and the last group was pre-treated with MLT 30 min before the QA injection. Immunoblots, oxidative stress biomarkers, histological assay of astrocytes and neurons were evaluated as well as rotarod and open field tests. There was a reduction in proteins levels of BDNF and NeuN in QA mice. Contrary effects in lysates showed NF-κB, IκBα, HTT, GFAP and NRs. The analysis of CAT, SOD, Gpx and GSH showed decreased activity, while MDA displayed increased activation in QA mice. The animals pre-treated with MLT revers the tendency of proteins and antioxidant biomarkers; the HTT perinuclear staining in neurons was reduced. NeuN histochemistry showed a greater number of NeuN + cells; the astrogliosis was attenuated; and locomotor activities improved. Analysis of RT-PCR do no show significant diferences between teatments. This study suggests that MLT can induce a compensatory response to neurotoxic stress againts neuro-glial injury. Thus, increasing MLT levels may be a promising treatment for HD disorder.

Keywords: HD; QA; MLT; Astrogliosis; NRs; NF-kB; BDNF

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