Time course study of microglial and behavioral alterations induced by 6-hydroxydopamine in rats.
Understanding the mechanisms responsible for nonmotor manifestations of Parkinson's disease (PD) is crucial in the search for new therapeutic approaches. The aim of the present study was to evaluate the time course of behavioral, neurochemical, and microglial responses after a retrograde partial lesion of the nigrostriatal pathway induced by bilateral injection of 6-hydroxydopamine (6-OHDA). The results showed that 6-OHDA was able to produce both anhedonic and anxiety behaviors; however, an increase of microglial density in some brain areas (substantia nigra, hippocampus and striatum) and deficits in locomotor activity was observed only one week after the lesion. Striatal levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were reduced by approximately 60% at all times tested. Conversely, increased levels of serotonin (5-HT) and its metabolite were also noted in the striatum only at the first week. These data extend our previous findings and suggest that the retrograde and partial damage of dopaminergic neurons in the substantia nigra can induce effects resembling premotor symptoms of PD, two and three weeks after injury.
Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: pereiras.thiago@outlook.com.
Thiago Pereira da
TP
Silva
Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Anicleto
A
Poli
Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Daniela Balz
DB
Hara
Department of Pharmacology, Biological Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Reinaldo Naoto
RN
Takahashi
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003863:Depression / Q000139:chemically induced / Q000523:psychology; D004195:Disease Models, Animal; D005518:Food Preferences; D006624:Hippocampus / Q000378:metabolism; D007113:Immunity, Innate; D008297:Male; D018782:Maze Learning; D017628:Microglia / Q000378:metabolism*; D009043:Motor Activity; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism* / Q000523:psychology*; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage
D015306:Biogenic Monoamines; D013395:Sucrose; D016627:Oxidopamine; D000118:Acetylglucosaminidase
6-Hydroxydopamine; Dopaminergic neurons; Neuroinflammation; Parkinson's disease