Systemic administration of 3-nitropropionic acid points out a different role for active caspase-3 in neurons and astrocytes

Neurochem Int. 2010 Feb;56(3):443-50. doi: 10.1016/j.neuint.2009.12.001. Epub 2009 Dec 5.

Abstract

The intraperitoneal administration of 3-nitropropionic acid, which is commonly used to induce toxicity models of Huntington's disease in experimental animals, produces severe brain injury in the lateral part of the striatum. We studied the presence of active caspase-3 in neurons and astrocytes from brains of rats treated with 3-nitropropionic acid following a subacute administration protocol. Active caspase-3 was almost absent in the core of the striatal lesion. However, it was expressed, albeit weakly, in the neurons present in the rim of the lesion. In cortex and non-injured striatal areas, and in the cortex and striatum of control animals, active caspase-3 staining was widely distributed and vivid, but localized in the cell bodies of astrocytes rather than in neurons. In treated animals, some of the active caspase-3 positive neurons localized in the rim of the lesion were also positive for TUNEL staining. This indicates the presence of a caspase-mediated apoptotic process. TUNEL was not present in control animals or in the astrocytes of treated animals. Thus, the presence of active caspase-3 in astrocytes may be merely constitutive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Astrocytes / drug effects
  • Astrocytes / enzymology*
  • Astrocytes / pathology
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism*
  • Convulsants / toxicity
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Huntington Disease / enzymology
  • Huntington Disease / physiopathology
  • In Situ Nick-End Labeling
  • Male
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects
  • Neurons / enzymology*
  • Neurons / pathology
  • Neurotoxins / toxicity
  • Nitro Compounds / toxicity*
  • Propionates / toxicity*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Convulsants
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • Caspase 3
  • 3-nitropropionic acid