PACAP-mediated neuroprotection of neurochemically identified cell types in MSG-induced retinal degeneration

J Mol Neurosci. 2008 Nov;36(1-3):97-104. doi: 10.1007/s12031-008-9059-5. Epub 2008 Apr 17.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is neuroprotective in animal models of different brain pathologies and injuries, including cerebral ischemia, Parkinson's disease, and different types of retinal degenerations. We have previously shown that PACAP is protective against monosodium glutamate (MSG)-induced retinal degeneration, where PACAP-treated retinas has more retained structure and PACAP induces anti-apoptotic while it inhibits pro-apoptotic signaling pathways. The aim of the present study was to investigate cell-type specific effects of PACAP in MSG-induced retinal degeneration by means of immunohistochemistry. Rat pups received MSG (2 mg/g b.w.) applied on postnatal days 1, 5, and 9. PACAP (100 pmol in 5 microl saline) was injected into the right vitreous body, while the left eye received only saline. Retinas were processed for immunocytochemistry after 3 weeks. Immunolabeling was determined for vesicular glutamate transporter 1, tyrosine hydroxylase, calretinin, calbindin, parvalbumin, and vesicular gamma-aminobutyric acid (GABA) transporter. In the MSG-treated retinas, the cell bodies and processes in the inner nuclear, inner plexiform, and ganglion cell layers displayed less immunoreactivity for all antisera. Apart from photoreceptors, only one major retinal cell type examined in this study; the calbindin-immunoreactive horizontal cell seemed not to be affected by MSG application. After simultaneous application of MSG and PACAP, staining of retinas was similar to that of normal eyes, with no significant alterations in immunoreactive patterns. These findings further support the neuroprotective function of PACAP in MSG-induced retinal degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 2
  • Calbindins
  • Food Additives / pharmacology
  • Immunohistochemistry
  • Neuroprotective Agents / metabolism*
  • Parvalbumins / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism*
  • Rats
  • Rats, Wistar
  • Retina* / cytology
  • Retina* / drug effects
  • Retina* / pathology
  • Retinal Degeneration* / chemically induced
  • Retinal Degeneration* / pathology
  • S100 Calcium Binding Protein G / metabolism
  • Sodium Glutamate / pharmacology*
  • Tyrosine 3-Monooxygenase / metabolism
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism

Substances

  • Calb2 protein, rat
  • Calbindin 2
  • Calbindins
  • Food Additives
  • Neuroprotective Agents
  • Parvalbumins
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • S100 Calcium Binding Protein G
  • Slc17a7 protein, rat
  • Slc32a1 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Tyrosine 3-Monooxygenase
  • Sodium Glutamate