Early cognitive impairment behind nigro-striatal circuit neurotoxicity: are astrocytes involved?

HERRERA M.; GHERSI MARISA; ARTUR DE LA VILLARMOIS E.; DEZA-PONZIO R.; VIRGOLINI M.; PEREZ MARIELA; MOLINA V.; BELLINI M. *EQUALLY CONTRIBUTION; HEREÑÚ CLAUDIA*EQUALLY CONTRIBUTION

ASN Neuro

SAGE Journal

Lugar: Illinois; Año: 2020

1759-0914

Cognitive dysfunction is one of the most severe non-motor symptoms ofnigro-striatal impairment. This occurs as a result of functional andmorphological changes of different neuronal circuits, includingmodifications in the plasticity and architecture of hippocampal synapses.Such alterations can be implicated in the genesis andprogression of dementia associated with neurodegenerative diseasesincluding parkinson-like symptoms. The aim of the present study was tocharacterize the onset of memory deficit after neurotoxicity with 6-hydroxydopamine (6-OHDA) in an animal model, and its correlation withhippocampal dysfunction. For this, we bilaterally microinjected 6-OHDAin dorsolateral Caudate-Putamen unit (CPu) and then, animals wereweekly tested for working memory, spatial short-term memory andmotor performance. We evaluated tyrosine hydroxylase as dopaminemarker, Aldehyde Dehydrogenase 2 mitochondrial detoxification enzymeand glial fibrillar acid protein astrocyte marker immunoreactivity indifferent involved areas: CPu, substantia nigra, prefrontal cortex andhippocampus. We observed a specific prefrontal cortex and nigro-striatalpathway TH reduction while ALDH2 showed a decrease-positive area inall the studied regions. Moreover, GFAP showed a specific CPu decreaseand hippocampus increase of positive areaat 3rd week after toxicity. Wealso evaluated the threshold to induce long- term potentiation ashippocampal excitability. Our findings showed reduced hippocampalsynaptic transmission accompanied by deficits in memory processes,without affecting motor performance at 3rd-week post 6-OHDAadministration. Our results suggest that, three weeks after neurotoxicadministration, astrocytes and ALDH2 mitochondrial enzymemodifications participate on altered properties that negatively affecthippocampal function and consequently cognitive behavior.