PMID- 32466659
OWN - NLM
STAT- MEDLINE
DCOM- 20210915
LR  - 20210915
IS  - 1759-0914 (Electronic)
IS  - 1759-0914 (Linking)
VI  - 12
DP  - 2020 Jan-Dec
TI  - Early Cognitive Impairment Behind Nigrostriatal Circuit Neurotoxicity: Are 
      Astrocytes Involved?
PG  - 1759091420925977
LID - 10.1177/1759091420925977 [doi]
LID - 1759091420925977
AB  - Cognitive dysfunction is one of the most severe nonmotor symptoms of 
      nigrostriatal impairment. This occurs as a result of profound functional and 
      morphological changes of different neuronal circuits, including modifications in 
      the plasticity and architecture of hippocampal synapses. Such alterations can be 
      implicated in the genesis and progression of dementia associated with 
      neurodegenerative diseases including Parkinson-like symptoms. There are few 
      studies regarding cognitive changes in nigrostriatal animal models. The aim of 
      this study was to characterize the onset of memory deficit after induction of 
      neurotoxicity with 6-hydroxydopamine (6-OHDA) and its correlation with 
      hippocampal dysfunction. For this, we bilaterally microinjected 6-OHDA in 
      dorsolateral Caudate-Putamen unit (CPu) and then, animals were tested weekly for 
      working memory, spatial short-term memory, and motor performance. We evaluated 
      tyrosine hydroxylase (TH) as a dopamine marker, aldehyde dehydrogenase 2 (ALDH2), 
      a mitochondria detoxification enzyme and astrocyte glial fibrillar acid protein 
      (GFAP) an immunoreactivity marker involved in different areas: CPu, substantia 
      nigra, prefrontal cortex, and hippocampus. We observed a specific prefrontal 
      cortex and nigrostriatal pathway TH reduction while ALDH2 showed a 
      decrease-positive area in all the studied regions. Moreover, GFAP showed a 
      specific CPu decrease and hippocampus increase of positively stained area on the 
      third week after toxicity. We also evaluated the threshold to induce long-term 
      potentiation in hippocampal excitability. Our findings showed that reduced 
      hippocampal synaptic transmission was accompanied by deficits in memory 
      processes, without affecting motor performance on the third-week post 6-OHDA 
      administration. Our results suggest that 3 weeks after neurotoxic administration, 
      astrocytes and ALDH2 mitochondrial enzyme modifications participate in altering 
      the properties that negatively affect hippocampal function and consequently 
      cognitive behavior.
FAU - Herrera, Macarena L
AU  - Herrera ML
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
AD  - Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP-CONICET), 
      Facultad de Ciencias Medicas, Universidad Nacional de La Plata,  Buenos Aires, 
      Argentina.
FAU - Deza-Ponzio, Romina
AU  - Deza-Ponzio R
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - Ghersi, Marisa S
AU  - Ghersi MS
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - de la Villarmois, Emilce A
AU  - de la Villarmois EA
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - Virgolini, Miriam B
AU  - Virgolini MB
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - Perez, Mariela F
AU  - Perez MF
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - Molina, Victor A
AU  - Molina VA
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
FAU - Bellini, Maria J
AU  - Bellini MJ
AD  - Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP-CONICET), 
      Facultad de Ciencias Medicas, Universidad Nacional de La Plata,  Buenos Aires, 
      Argentina.
FAU - Herenu, Claudia B
AU  - Herenu CB
AUID- ORCID: 0000-0002-3135-7024
AD  - Instituto de Farmacologia Experimental de Cordoba (IFEC-CONICET), 
      Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional 
      de Cordoba.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - ASN Neuro
JT  - ASN neuro
JID - 101507115
RN  - 8HW4YBZ748 (Oxidopamine)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*pathology
MH  - Cognitive Dysfunction/chemically induced/*pathology/psychology
MH  - Corpus Striatum/drug effects/*pathology
MH  - Locomotion/drug effects/physiology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Oxidopamine/*toxicity
MH  - Parkinsonian Disorders/chemically induced/*pathology/psychology
MH  - Rats
MH  - Rats, Wistar
MH  - Substantia Nigra/drug effects/*pathology
PMC - PMC7263115
OTO - NOTNLM
OT  - 6-OHDA
OT  - ALDH2
OT  - astrocytes
OT  - cognitive dysfunction
OT  - neurotoxicity
OT  - synaptic plasticity
EDAT- 2020/05/30 06:00
MHDA- 2021/09/16 06:00
PMCR- 2020/05/28
CRDT- 2020/05/30 06:00
PHST- 2020/05/30 06:00 [entrez]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/09/16 06:00 [medline]
PHST- 2020/05/28 00:00 [pmc-release]
AID - 10.1177_1759091420925977 [pii]
AID - 10.1177/1759091420925977 [doi]
PST - ppublish
SO  - ASN Neuro. 2020 Jan-Dec;12:1759091420925977. doi: 10.1177/1759091420925977.