Disorders of the Nervous System
Author: Felix Fares Taie | Email: ffarestaie@fmed.uba.ar
Félix Fares Taie1°2°, Agostina Stahl1°2°, Germán La Iacona1°2°, Irene Taravini3°, Gustavo Murer1°2°, Lorena Rela1°2°
1° Universidad de Buenos Aires, Facultad de Medicina, Departamento de Ciencias Fisiológicas, Buenos Aires, Argentina
2° CONICET, Universidad de Buenos Aires, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), Buenos Aires, Argentina
3° Laboratorio de Neurobiología Experimental. LNE-ICTAER-UNER-CONICET, Gualeguaychú, Entre Ríos, Argentina
Dopaminergic denervation of the striatum results in medium spiny neurons (MSN) dendritic spine loss. Microglia—central nervous system’s immune myeloid cells—react to inflammation associated with neurodegenerative processes, and potentially enhance their phagocytic activity.
This study aims at examining whether inhibiting microglial reactivity can provide therapeutic benefits and/or prevent the dendritic spine pruning of MSN.
We induced hemi-parkinsonism in D1-Tomato mice by injecting the toxin 6-OHDA into the left medial forebrain bundle. Control mice experienced a sham lesion. After one week to allow for complete denervation in parkinsonian mice, half the animals in each group received doxycycline in the drinking water for five weeks to inhibit microglial reactivity, while the other half drank regular water. Following treatment, tissue underwent immunohistochemical analysis, and we quantified the dendritic spine density of MSN.
Our results replicated the reduction in dendritic spine density in MSN in parkinsonian animals compared to sham-controls. A significant increase in dendritic spine density was observed in MSN of parkinsonian mice following doxycycline treatment, with an increased proportion of spines with immature morphology. We observed no significant improvements in global locomotion.
These results contribute to the hypothesis of microglial involvement in striatal circuit remodeling, in addition to its participation in dopaminergic neuron loss.