Olfactory Training Prevents Olfactory Dysfunction Induced by Bulbar Excitotoxic Lesions: Role of Neurogenesis and Dopaminergic Interneurons

• Published in: Molecular neurobiology 2019-12, Vol.56 (12), p.8063-8075
• Main Authors: Marin, Concepció, Laxe, Sara, Langdon, Cristobal, Alobid, Isam, Berenguer, Joan, Fuentes, Mireya, Bernabeu, Montserrat, Mullol, Joaquim
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Central nervous system; Discrimination Learning - drug effects; Discrimination Learning - physiology; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - physiology; Excitatory Amino Acid Agonists - toxicity; Excitotoxicity; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Interneurons; Interneurons - drug effects; Interneurons - physiology; Lesions; Male; Movement disorders; N-Methyl-D-aspartic acid receptors; N-Methylaspartate - toxicity; Neurobiology; Neurodegenerative diseases; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neurology; Neuroprotection; Neurosciences; Odorants; Olfaction; Olfaction disorders; Olfaction Disorders - chemically induced; Olfaction Disorders - physiopathology; Olfactory bulb; Olfactory Bulb - drug effects; Olfactory Bulb - pathology; Olfactory Bulb - physiology; Olfactory discrimination; Olfactory discrimination learning; Parkinson's disease; Pramipexole; Rats; Rats, Sprague-Dawley; Smell - drug effects; Smell - physiology; Subventricular zone; Traumatic brain injury
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-019-1639-6

Glutamatergic excitotoxicity is involved in pathologies affecting the central nervous system, including traumatic brain injury (TBI) and neurodegenerative diseases, such as Parkinson’s disease (PD), in which olfactory dysfunction is an early symptom. Interestingly, our group has recently shown that bilateral administration of the glutamate agonist, N -methyl- d -aspartate (NMDA) in the olfactory bulbs (OBs) induces an olfactory dysfunction 1 week after lesions. Although a wide range of treatments have been attempted, no standard therapy has been established to treat olfactory disorders. Increasing evidence suggests a beneficial effect of olfactory training (OT) in olfactory function. However, the mechanisms underlying OT effects remain unknown. We investigated the effects of OT on the olfactory dysfunction induced by excitotoxicity in bilateral OB NMDA–lesioned animals. We compared OT effects with the ones obtained with neuroprotective therapies (pramipexole and MK801). We studied the underlying mechanisms involved in OT effects investigating the changes in the subventricular zone (SVZ) neurogenesis and in the number of periglomerular dopaminergic interneurons. One week after lesion, NMDA decreased the number of correct trials in the olfactory discrimination tests in the non-trained group ( p