2. Academic Validation
  3. Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB

Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB

  • Brain Res. 2021 Oct 1:1768:147577. doi: 10.1016/j.brainres.2021.147577.
Agata Płoska 1,  Paulina Cieślik 2,  Anna Siekierzycka 3,  Leszek Kalinowski 4,  Joanna M Wierońska 5
Affiliations

Affiliations

  • 1 Medical University of Gdansk, Department of Medical Laboratory Diagnostics - Biobank Fahrenheit BBMRI.pl, Debinki Street 7, 80-211 Gdansk, Poland; Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7, 80-211 Gdansk, Poland. Electronic address: agata.ploska@gumed.edu.pl.
  • 2 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 12 Smętna Street, 31-343 Kraków, Poland. Electronic address: cieslik@if-pan.krakow.pl.
  • 3 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 12 Smętna Street, 31-343 Kraków, Poland. Electronic address: anna.siekierzycka@gumed.edu.pl.
  • 4 Medical University of Gdansk, Department of Medical Laboratory Diagnostics - Biobank Fahrenheit BBMRI.pl, Debinki Street 7, 80-211 Gdansk, Poland; Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7, 80-211 Gdansk, Poland; BioTechMed Center/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Narutowicza 11/12, 80-223 Gdansk, Poland. Electronic address: leszek.kalinowski@gumed.edu.pl.
  • 5 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 12 Smętna Street, 31-343 Kraków, Poland. Electronic address: wierons@if-pan.krakow.pl.
PMID: 34217728 DOI: 10.1016/j.brainres.2021.147577
Abstract

The olfactory bulbectomized (OBX) rat model is a well-established model of depression in which antidepressant drugs reverse deficits in the passive avoidance test 14 days after administration. Recently, the olfactory bulbectomized rat model has been proposed to be a model of Alzheimer's disease (AD), and the available data indicate similarities between the changes that typically occur in AD and those observed in OBX Animals. In the present study, the occurrence of neurochemical impairments related to AD were investigated 8 months after OB ablation. The expression of the nitric oxide synthases eNOS and nNOS, receptor for advanced glycation endproducts (RAGEs) and dimethylarginine dimethylaminohydrolase (DDAH1) in the prefrontal cortices (PFCs), hippocampi and striata of olfactory bulbectomized and sham-operated rats was evaluated. Subsequently, the impact of the administration of a positive allosteric modulator of the mGlu5 receptor, CDPPB (14 days, 2.5 or 5 mg/kg), on OBX-related changes was assessed. OB ablation induced typical deficits in passive avoidance. Significant aberrations in the expression of both isoforms of NOS were observed in the hippocampus and striatum, and the expression of DDAH1 was increased in the PFCs of OBX Animals. CDPPB at a dose of 5 mg/kg ameliorated cognitive impairment in the passive avoidance test and partially reversed the changes in eNOS and nNOS expression induced by the lesion. The results of this study confirm that some of the neurochemical changes observed in OBX Animals may resemble those associated with AD pathology and that activation of the mGlu5 receptor may partially counteract these pathological alterations.

Keywords

Endothelial nitric oxide synthase; Metabotropic glutamate receptor 5; Neuronal nitric oxide synthase; Nitric oxide; Olfactory bulbectomy.

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