Repeated Heat Exposure Impairs Nigrostriatal Dopaminergic Neurons in Mice

Abstract

Environmental heat stress is associated with physical stress responses, including changes in monoamines, protein expression, and neuronal circuits and damage to neurons in the brain. This study determined the effects of heat stress on the nigrostriatal dopaminergic system based on behavioral, histological, and neurochemical analyses. To evaluate behavioral changes after heat exposure, we subjected mice to the pole and open field tests. The data suggested that heat stress for 7 d significantly impaired movement. Then, we conducted a histological analysis using tyrosine hydroxylase (TH) immunoreactivity in the striatum and substantia nigra (SN). Heat stress induced a significant deficit in TH-positive fibers and cells after 14-and 21-d exposure, respectively. We also measured the striatal dopamine (DA), 4-hydroxy-3-methoxy-phenylacetic acid, and 3,4-dihydroxyphenylacetic acid levels. The data suggested that DA turnover rate increased with heat exposure in a time-dependent manner, resulting in the significant decrease of DA after 28 d. Moreover, the expression of heat shock protein 70 (HSP70) was increased in the mouse SN with up to 14-d heat exposure, but decreased after 21 d of the stress. And glucose-regulated protein 78 (GRP78) was gradually increased in the mouse SN with 28-d heat exposure. The caspase-3 activity was also increased after 14-d heat exposure. These findings are the first evidence that repeated heat stress impairs nigrostriatal dopaminergic neurons, motor function, and DA availability with changes of HSP70 and GRP78 expressions and caspase-3 activity in mice.Key words repeated heat stress; dopaminergic neuron; heat shock protein 70; glucose-regulated protein 78; caspase-3 Extreme environmental temperatures induce systemic metabolic disorders accompanied by hyperthermia, behavioral, physiological, and biochemical changes, which might be considered pathophysiological indices for assessing heat stress.

Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon

“…In addition, other dopaminergic genes - DBH , TH , and ADCY1 - were also down-regulated by HS. This is consistent with the finding that heat stress reduces TH immunoreactivity in striatal dopamine neurons in mice and impairs nigrostriatal dopaminergic neurons and motor function [58].…”

Heat stress-induced memory impairment is associated with neuroinflammation in mice

“…To clearly elucidate the heat-cognition relationship, we examined the dependency on heat exposure time. Based on a previous report [6, 14], we chose the following experimental methods and conditions: humidity (60 ± 10 %), temperature (43 °C), exposure duration (15 min/day), subject number (n = 12), and memory test paradigms (Y-maze, novel object recognition task, and passive avoidance test). By conducting a longitudinal study, we clearly demonstrated that heat exposure per se had an inhibitory effect on cognition in mice.…”

“…A number of studies showed that heat stress can cause cell death in the brain [6, 35, 36, 50]. Activated glial cells in the brain produce neurotoxic factors that subsequently lead to neuronal death [44].…”

“…Many reports demonstrated that heat stress induces various physiological and pathophysiological responses, such as heat adaptation, hyperthermia, hypoglycemia, water loss, gastric hemorrhage, spermatogenic dysfunction, systemic metabolic disorders, increased blood pressure and heart rate, decreased food consumption and body weight gain, and increased blood glucocorticoid levels and vasopressin release [1–5]. In addition, a number of studies also showed that thermal stress has a profound impact on brain structure and function, leading to neural circuit modification, neuronal loss, neurological defects, convulsions, heat stroke, and accelerated brain dysfunction induced by insults [6–11]. In view of global warming, heat-related diseases have attracted much concern among researchers.…”

Association analysis between SNPs in the 5'-flanking region of the chicken GRP78 gene, thermotolerance parameters, and tissue mRNA expression

“…Jia et al (2013) found that pretreatment with prostaglandin E1 and somatostatin alleviated ER stress by the induction of HSP70 (another member of the HSP70 family) and GRP78. Kim et al (2013) demonstrated that GRP78 gradually increased in the mouse substantia nigra with 28-day heat exposure. Recently, GRP78 expression was found to be related to disease occurrence.…”