Recovery of Olfactory Function After Excitotoxic Lesion of the Olfactory Bulbs Is Associated with Increases in Bulbar SIRT1 and SIRT4 Expressions

• Published in: Molecular neurobiology 2019-08, Vol.56 (8), p.5643-5653
• Main Authors: Marin, Concepció, Langdon, Cristobal, Alobid, Isam, Fuentes, Mireya, Bonastre, Mercè, Mullol, Joaquim
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Dopamine receptors; Excitotoxicity; Glutamatergic transmission; Glutamic acid receptors; Interneurons; Lesions; Male; Molecular modelling; N-Methyl-D-aspartic acid; N-Methylaspartate; NAD; Neurobiology; Neurodegenerative diseases; Neurogenesis; Neurology; Neurosciences; Neurotoxins - toxicity; Olfaction; Olfactory bulb; Olfactory Bulb - drug effects; Olfactory Bulb - pathology; Olfactory Bulb - physiopathology; Olfactory discrimination; Olfactory discrimination learning; Parkinson's disease; Proteins; Rats, Sprague-Dawley; Rodents; SIRT1 protein; Sirtuin 1 - metabolism; Sirtuins; Sirtuins - metabolism; Smell - drug effects; Spontaneous recovery; Subventricular zone; Traumatic brain injury
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-019-1472-y

Excitotoxicity consists in a cascade of intracellular events initiated by an excessive release of glutamate and hyperactivation of glutamatergic receptors that is involved in several pathologies, including traumatic brain injury and neurodegenerative diseases such as Parkinson’s disease. Both disorders are a common cause of olfactory dysfunction. We previously reported a role for glutamate excitotoxicity in olfactory dysfunction showing an olfactory deficit 1 week after lesion and a spontaneous recovery 2 weeks after excitotoxicity lesion of the olfactory bulbs (OBs). The olfactory dysfunction recovery was associated with an increase in subventricular zone neurogenesis and an increase in the OB glomerular dopaminergic interneurons. However, the underlying molecular mechanisms involved in the OB dopaminergic differentiation and olfactory recovery are still unknown. To investigate the role of silent information regulator family proteins sirtuins (SIRTs), a family of NAD+-dependent histone deacetylases, on the olfactory function recovery, we examined the OB SIRT (SIRT1, SIRT2, and SIRT4) expressions after OB excitotoxic lesions in rodents. N -methyl- d -aspartate (NMDA) OB administration induced a decrease in the number of correct choices in the discrimination tests 1 week after lesions ( p