Oral administration of BDNF and/or GDNF normalizes serum BDNF level in the olfactory bulbectomized rats: A proof of concept study.
Administration, Oral
Animals
Biological Transport
Blood-Brain Barrier
/ drug effects
Brain Diseases
/ blood
Brain-Derived Neurotrophic Factor
/ administration & dosage
Disease Models, Animal
Male
Nerve Growth Factors
/ administration & dosage
Olfactory Bulb
/ surgery
Proof of Concept Study
Rats, Sprague-Dawley
Recombinant Proteins
BDNF
GDNF
Neurotrophins
Olfactory bulbectomy
Rats
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
20
09
2018
revised:
08
02
2019
accepted:
11
03
2019
pubmed:
14
6
2019
medline:
17
1
2020
entrez:
14
6
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31195344
pii: S1734-1140(18)30551-6
doi: 10.1016/j.pharep.2019.03.005
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
CDNF protein, human
0
Nerve Growth Factors
0
Recombinant Proteins
0
BDNF protein, human
7171WSG8A2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
669-675Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.