Oral administration of BDNF and/or GDNF normalizes serum BDNF level in the olfactory bulbectomized rats: A proof of concept study

Pharmacol Rep. 2019 Aug;71(4):669-675. doi: 10.1016/j.pharep.2019.03.005. Epub 2019 Mar 16.

Abstract

Background: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier.

Methods: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid.

Results: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit.

Conclusion: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.

Keywords: BDNF; GDNF; Neurotrophins; Olfactory bulbectomy; Rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Transport
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Brain Diseases / blood*
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / blood*
  • Brain-Derived Neurotrophic Factor / cerebrospinal fluid
  • Disease Models, Animal
  • Male
  • Nerve Growth Factors / administration & dosage
  • Nerve Growth Factors / blood*
  • Nerve Growth Factors / cerebrospinal fluid
  • Olfactory Bulb / surgery
  • Proof of Concept Study
  • Rats, Sprague-Dawley
  • Recombinant Proteins

Substances

  • Brain-Derived Neurotrophic Factor
  • CDNF protein, human
  • Nerve Growth Factors
  • Recombinant Proteins
  • BDNF protein, human