Olfactory function in an excitotoxic model for secondary neuronal degeneration: Role of dopaminergic interneurons

Abstract

Secondary neuronal degeneration (SND) occurring in Traumatic brain injury (TBI) consists in downstream destructive events affecting cells that were not or only marginally affected by the initial wound, further increasing the effects of the primary injury. Glutamate excitotoxicity is hypothesized to play an important role in SND. TBI is a common cause of olfactory dysfunction that may be spontaneous and partially recovered. The role of the glutamate excitotoxicity in the TBI-induced olfactory dysfunction is still unknown.We investigated the effects of excitotoxicity induced by bilateral N-Methyl-D-Aspartate (NMDA) OB administration in the olfactory function, OB volumes, and subventricular zone (SVZ) and OB neurogenesis in rats. NMDA OB administration induced a decrease in the number of correct choices in the olfactory discrimination tests one week after lesions (p<0.01), and a spontaneous recovery of the olfactory deficit two weeks after lesions (p<0.05). A lack of correlation between OB volumes and olfactory function was observed. An increase in SVZ neurogenesis (Ki67+ cells, PSANCAM+ cells (p<0.01) associated with an increase in OB glomerular dopaminergic immunostaining (p<0.05) were related to olfactory function recovery.The present results show that changes in OB volumes cannot explain the recovery of the olfactory function and suggest a relevant role for dopaminergic OB interneurons in the pathophysiology of recovery of loss of smell in TBI.