In vivo stress and chronic glucocorticoid exposure influence the neuroinflammation and dopaminergic neurotoxicity associated with methamphetamine

Details

• Personal Author:
  Bowyer JF ; Kelly KA ; Miller DB ; O'Callaghan JP
• Description:
  Upregulation of proinflammatory cytokines/chemokines in brain ("neuroinflammation") accompanies brain injury/disease and systemic infections. Following nerve terminal damage after acute exposure to dopaminergic neurotoxicant, methamphetamine (METH), we documented elevated neuroinflammation, which may serve as a modulator or mediator of astroglial/microglial activation. Activated glia (associated with all types of brain injury) may be neuroprotective or exacerbate neural damage. Our prior genetic and pharmacological interventions have resulted in partial suppression of METH induced neuroinflammation without affecting neurotoxicity/astrogliosis. Here, mice were pretreated with the stress hormone corticosterone (CORT;400 mg/L drinking water) for 1 week or repeated in vivo stress for 5d, consisting of social reorganization and cage shaking. METH administration alone (20mg/kg,s.c.) caused significant increases in proinflammatory cytokine (TNFalpha,IL6,CCL2,IL1beta,LIF,OSM) mRNA expression in striatum at 12h. By 72h marked astrocytic hypertrophy (GFAP protein/immunohistochemistry(IHC)), microglial activation (isolectin IHC) and dopaminergic nerve terminal damage (TH protein /IHC) was observed in striatum. Chronic CORT pretreatment caused exacerbated inflammation, astrocyte hypertrophy and microglial activation after METH exposure in the striatum, hippocampus and cortex. Of note, chronic CORT pretreatment exacerbated METH-induced decreases in TH protein (to 10% of control) in striatum. However, repeated in vivo stress exposure completely blocked striatal dopaminergic neurotoxicity and reduced the neuroinflammatory response to METH. As the levels of chronic CORT approached or exceeded those associated with high physiological stress, our data suggest that chronic CORT therapy or sustained physiological stress sensitizes the CNS neuroinflammatory and neurotoxic responses to METH. Also, more severe or prolonged in vivo stressor application may be required to produce priming of the CNS similar to exogenous CORT. [Description provided by NIOSH]
• Subjects:
  Adrenal Cortex Hormones Chronic Disease Endocrine System Environmental Monitoring Histocytochemistry Immune System Laboratories Nervous System Occupational Exposure Occupational Health Safety Substance-Related Disorders

  More +
• Keywords:
  Brain-function Brain-matter Chronic-exposure Chronic-inflammation Corticoids Corticosteroids Cytochemistry Drug-abuse Exposure-assessment Exposure-levels Histochemical-analysis Hormone-activity Hormones Immune-reaction Immunochemistry In-vivo-study Laboratory-animals Laboratory-testing Nerve-damage Neurological-reactions Neurophysiological-effects Neurotoxins Pharmacodynamics Proteins Stress

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Arkansas ; California ; OSHA Region 3 ; OSHA Region 6 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  220-221
• Volume:
  126
• NIOSHTIC Number:
  nn:20040617
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):220-221
• CAS Registry Number:
  Dopamine (CAS RN 51-61-6) ; Methamphetamine (CAS RN 537-46-2)
• Federal Fiscal Year:
  2012
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a670c0b28075cb7140b334aa40e783e7ed435ad08ec764e1ffc9f34d98ee3a1c373af3ca0de2afb5abd3e582426608f890d3f127fa06adae35d638bd0c050fd9
• Download URL:
  https://stacks.cdc.gov/view/cdc/193416/cdc_193416_DS1.pdf
• File Type:
  [PDF - 486.47 KB ]