Notwithstanding major advances in psychotherapeutics, their efficacy and specificity remain limited. The slow onset of beneficial outcomes and numerous adverse effects of widely used medications remain of chief concern, warranting in-depth studies. The majority of frontline therapies are thought to enhance the endogenous monoaminergic drive, to initiate a cascade of molecular events leading to lasting functional and structural plasticity. They also involve alterations in trophic factor signalling, including brain-derived neurotrophic factor (BDNF), VGF (non-acronymic), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), glial cell-derived neurotrophic factor (GDNF), and others. In several major mental disorders, emerging data suggest protective and restorative effects of trophic factors in preclinical models, when applied on their own. Antidepressant outcomes of VGF and FGF2, for instance, were shown in experimental animals, while BDNF and GDNF prove useful in the treatment of addiction, schizophrenia, and autism spectrum disorders. The main challenge with the effective translation of these and other findings in the clinic is the knowledge gap in action mechanisms with potential risks, as well as the lack of effective platforms for validation under clinical settings. Herein, we review the state-of-the-art and advances in the therapeutic use of trophic factors in several major neuropsychiatric disorders.
- MeSH
- duševní poruchy farmakoterapie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nanočásticový lékový transportní systém * MeSH
- neuroplasticita účinky léků MeSH
- neurotrofní faktory aplikace a dávkování MeSH
- přehledová literatura jako téma MeSH
- preklinické hodnocení léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
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.
- MeSH
- aplikace orální MeSH
- biologický transport MeSH
- bulbus olfactorius chirurgie MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor aplikace a dávkování krev mozkomíšní mok MeSH
- nemoci mozku krev MeSH
- neurotrofní faktory aplikace a dávkování krev mozkomíšní mok MeSH
- ověření koncepční studie MeSH
- potkani Sprague-Dawley MeSH
- rekombinantní proteiny MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The focus of this study was to compare the role of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the regeneration of experimental skin and cartilage trauma. The role of VEGF in this process is known since decade; the NGF participation on this process has been first discussed within the spinal cord injury repair. We hypothesized that both VEGF and NGF induce angiogenesis and take part on the repair process. The angiogenesis response and the cartilage regeneration after phVEGF(165) plasmid and rat pcNGF plasmid administration were investigated using BALB/c mice. PhVEGF(165) and pcNFG were injected into the right mice ear and plain vector injection into the left ear the day before trauma. The next day, all mice were ear-punched, resulting in 2-mm diameter puncture through the center of both pinnae. In BALB/c mouse strain, a significantly faster cartilage repair was observed after phVEGF(165) and pcNGF injection into punched ear area in comparison to the control group. It has been shown that the healing process is after VEGF and NGF injection driven differentially. In case of VEGF is the cartilage wound repaired by induction of new chondrocytes differentiation. In the case of NGF, the regeneration is supported by immature leukocytes attracted into the punched area. The leukocytes induct angiogenesis so far indirectly by inflammation. The NGF-induced inflammation environment may be a part of mosaic creating the complete picture of regeneration.
- MeSH
- chondrogeneze * účinky léků fyziologie MeSH
- fyziologická neovaskularizace * účinky léků fyziologie MeSH
- genetické vektory MeSH
- hojení ran * účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- kůže zranění MeSH
- látky indukující angiogenezi aplikace a dávkování MeSH
- modely u zvířat MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neurotrofní faktory * aplikace a dávkování genetika MeSH
- plazmidy MeSH
- ušní chrupavka zranění fyziologie MeSH
- vaskulární endoteliální růstový faktor A * aplikace a dávkování genetika MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
