Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation

• Published in: Neuroscience 2017-09, Vol.358, p.79-92
• Main Authors: Chauhan, Nishant Ranjan, Kapoor, Medha, Prabha Singh, Laxmi, Gupta, Rajinder Kumar, Chand Meena, Ramesh, Tulsawani, Rajkumar, Nanda, Sarita, Bala Singh, Shashi
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - metabolism; Analysis of Variance; Animals; Biogenic Monoamines - metabolism; Blood Pressure - physiology; Body Temperature - physiology; Corticotropin-Releasing Hormone - metabolism; Cyclooxygenase 2 - metabolism; Encephalitis - etiology; Encephalitis - pathology; Encephalitis - physiopathology; Glial Fibrillary Acidic Protein - metabolism; glutamate; Heart Rate - physiology; heat-stress; Hot Temperature - adverse effects; hypothalamus; Male; monoamines; neuroinflammation; NF-kappa B - metabolism; oxidative stress; Oxidative Stress - physiology; Random Allocation; Rats; Rats, Sprague-Dawley; Zearalenone - analogs & derivatives; Zearalenone - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.06.023

•Baroreflex responsiveness is intact under Moderate HS and early stages of Severe HS.•HTH elicits normal neurotransmitter release in response to Moderate HS.•Severe HS induces neuroinflammation in HTH causing Monoamines & Glu imbalance culminating in thermoregulatory dysfunction. Heat Stress (HS) induces diverse pathophysiological changes, which include brain ischemia, oxidative stress and neuronal damage. The present study was undertaken with the objective to ascertain whether neuroinflammation in Hypothalamus (HTH) caused under HS affects monoamine levels and hence, its physiological role in thermoregulation. Rats were exposed to HS in a heat simulation environmental chamber (Ambient temperature, Ta=45±0.5°C and Relative Humidity, RH=30±10%) with real-time measurement of core temperature (Tc) and skin temperature (Ts). Animals were divided into two subgroups: Moderate HS (MHS) (Tc=40°C) and Severe HS (SHS)/Heat stroke (Tc=42°C). Rats with MHS showed an increase in Mean Arterial Pressure (MAP) and Heart Rate (HR) while fall in MAP and rise in HR was observed in rats with SHS. In addition, oxidative stress and an increase in pyknotic neurons were observed in HTH. High levels of Adrenocorticotropic-hormone (ACTH), Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) in the systemic circulation and progressive increase in EPI and DA levels in HTH were recorded after the thermal insult. Moreover, a substantial increase in Glutamate (Glu) level was observed in HTH as well as in systemic circulation of heat stroke rats. We found a rise in NE whereas a fall in Serotonin (5-HT) level in HTH at MHS, without perturbing inflammatory mediators. However, rats with SHS exhibited significant elevations in NF-kB, IL-1β, COX2, GFAP and Iba1 protein expression in HTH. In conclusion, the data suggest that SHS induces neuroinflammation in HTH, which is associated with monoamines and Glu imbalances, leading to thermoregulatory disruption.