Neuroprotective effects of hibernation-regulating substances against low-temperature-induced cell death in cultured hamster hippocampal neurons

• Published in: Brain research Vol. 1108; no. 1; pp. 107 - 116
• Main Authors: Tamura, Yutaka, Monden, Mayuko, Shintani, Mitsuteru, Kawai, Ami, Shiomi, Hirohito
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 07.09.2006; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine; Adenosine - pharmacology; Analgesics, Opioid - pharmacology; Animals; Biological and medical sciences; Body Temperature - physiology; Cell death; Cell Death - drug effects; Cell Death - physiology; Cells, Cultured; Cricetinae; Cultured hippocampal cell; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Hibernation; Hibernation - physiology; Hippocampus - metabolism; Histamine - pharmacology; Histamine H1 Antagonists - pharmacology; Hypothermia, Induced - adverse effects; Injections, Intraventricular; Narcotic Antagonists - pharmacology; Nerve Degeneration - drug therapy; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neurons - metabolism; Neuroprotective Agents - pharmacology; Opioid; Purinergic P1 Receptor Antagonists; Receptors, Opioid - drug effects; Receptors, Opioid - metabolism; Receptors, Purinergic P1 - metabolism; Syrian hamster; Thermoregulation. Hibernation. Estivation. Ecophysiology and environmental effects; Thyrotropin-Releasing Hormone - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Opioid; Syrian hamster; Adenosine; Cultured hippocampal cell; Cell death; Hibernation; Neuroprotection; Temperature; Rodentia; Central nervous system; Opiates; In vitro; Opioid peptide; Encephalon; Vertebrata; Mammalia; Animal; Hamster; Hippocampus
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.06.020

The neuroprotective effects of hibernation-regulating substances (HRS) such as adenosine (ADO), opioids, histamine and thyrotropin-releasing hormone (TRH) on low-temperature-induced cell death (LTCD) were examined using primary cultured hamster hippocampal neurons. LTCD was induced when cultures were maintained at <22 °C for 7 days. ADO (10–100 μM) protected cultured neurons from LTCD in a dose-dependent manner. The neuroprotective effects of ADO were reversed by both 8-cyclopenthyltheophilline (CPT; A 1 receptor antagonist) and 3,7-dimethyl-1-propargylxanthine (DMPX; A 2 receptor antagonist). Morphine (a non-selective opioid receptor agonist) was also effective in attenuating LTCD at an in vitro dose range of 10–100 μM. The neuroprotective effects of morphine were antagonized by naloxone (a non-selective opioid receptor antagonist). In addition, although [D-Ala 2, N-Me-Phe 4, Gly-ol 5]-enkephalin (DAMGO; μ-opioid receptor agonist), [D-Pen 2,5]-enkephalin (DPDPE; δ-opioid receptor agonist) and U-69593 (κ-opioid receptor agonist) were also effective, LTCD of cultured hippocampal neurons was not affected by TRH. Furthermore, histamine produced hypothermia in Syrian hamsters and protected hippocampal neurons in vitro at 100 μM. The neuroprotective effect of histamine was reversed by pyrilamine (H 1 receptor antagonist). Apoptosis was probably involved in LTCD. These results suggest that ADO protected hippocampal neurons in vitro via its agonistic actions on both A 1 and A 2 receptors, whereas morphine probably elicited its neuroprotective effects via agonistic effects on the μ-, δ- and κ-opioid receptors. In addition, histamine also protected hippocampal neurons via its agonistic action on the H 1 receptor. Thus, HRS-like adenosine-, opioid- and histamine-like hypothermic actions would most likely induce neuroprotective effects against LTCD in vitro.