The neuroprotective and neurogenic effects of neuropeptide Y administration in an animal model of hippocampal neurodegeneration and temporal lobe epilepsy induced by trimethyltin

J Neurochem. 2012 Jul;122(2):415-26. doi: 10.1111/j.1471-4159.2012.07770.x. Epub 2012 May 21.

Abstract

The effects of intracerebroventricular administration of neuropeptide Y (NPY), which is believed to play an important role in neuroprotection against excitotoxicity and in the modulation of adult neurogenesis, were evaluated in an animal model of hippocampal neurodegeneration and temporal lobe epilepsy represented by trimethyltin (TMT) intoxication. A single TMT injection (8 mg/kg) causes, in the rat brain, massive neuronal death, selectively involving pyramidal neurons, accompanied by glial activation and enhanced hippocampal neurogenesis. Our data indicate that intracerebroventricular administration of exogenous NPY (at the dose of 2 μg/2 μL, 4 days after TMT-administration), in adult rats, exerts a protective role in regard to TMT-induced hippocampal damage and a proliferative effect on the hippocampal neurogenic niche through the up-regulation of Bcl-2, Bcl2l1, Bdnf, Sox-2, NeuroD1, Noggin and Doublecortin genes, contributing to delineate more clearly the role of NPY in in vivo neurodegenerative processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Apoptosis Regulatory Proteins / biosynthesis
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Bromodeoxyuridine
  • Doublecortin Protein
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / drug therapy*
  • Epilepsy, Temporal Lobe / pathology*
  • Female
  • Gene Expression / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Immunohistochemistry
  • Injections, Intraventricular
  • Nerve Degeneration / etiology
  • Nerve Degeneration / prevention & control*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neurogenesis / drug effects*
  • Neurogenesis / genetics
  • Neuropeptide Y / administration & dosage
  • Neuropeptide Y / pharmacology*
  • Neuroprotective Agents*
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, Neuropeptide Y / drug effects
  • Trimethyltin Compounds*

Substances

  • Antimetabolites
  • Apoptosis Regulatory Proteins
  • Brain-Derived Neurotrophic Factor
  • Dcx protein, rat
  • Doublecortin Protein
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Neuroprotective Agents
  • Receptors, Neuropeptide Y
  • Trimethyltin Compounds
  • trimethyltin
  • RNA
  • Bromodeoxyuridine