Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice

Eur J Neurosci. 2011 Feb;33(4):689-98. doi: 10.1111/j.1460-9568.2010.07563.x. Epub 2011 Jan 13.

Abstract

Heterozygous reeler mice (HRM), haploinsufficient for reelin, have been proposed to be a genetic mouse model of schizophrenia. Beside behavioural similarities, HRM also demonstrate several neuroanatomical traits similar to patients suffering from schizophrenia. In the present study using immunocytochemical procedures, we investigated HRM and wild-type mice (WT) for differences in the numbers and densities of glutamic acid decarboxylase (GAD)67 and parvalbumin (PARV)-immunoreactive (IR) neurons in the hippocampus, tyrosine hydroxylase (TH)-IR neurons in the ventral tegmental area (VTA) and substantia nigra (SN), and serotonin transporter (5-HT-T)-IR neurons of the raphe nuclei. We found that HRM, compared with WT, show a significant decrease of GAD67-IR neurons in hippocampal subregion CA1 [stratum pyramidale (SP)], CA2 [stratum oriens (SO), stratum pyramidale (SP) and stratum radiatum (SR)] and dentate gyrus [granule cell layer (GL)], and also a significant decrease of PARV-containing neurons in CA1 (SO, SP) and CA2 (SP). No morphological differences were found in the SN/VTA or raphe nuclei. In conclusion, these results support a hippocampal γ-aminobutyric acid (GABA)ergic dysfunction in HRM as previously described by other authors, and may be based on a downregulation of GAD67 and PARV expressions. In summary, the reelin haploinsufficient mouse may provide a useful model for studying the interaction between reelin and hippocampal GABAergic system, its effect on dendritic spine maturation and plasticity related to schizophrenia.

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Neurologic Mutants*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Reelin Protein
  • Schizophrenia / physiopathology
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Biomarkers
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • gamma-Aminobutyric Acid
  • Tyrosine 3-Monooxygenase
  • RELN protein, human
  • Reln protein, mouse
  • Serine Endopeptidases
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1