Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson’s disease

Hernandez-Chan, Nancy G.; Bannon, Michael J.; Orozco-Barrios, Carlos E.; Escobedo, Lourdes; Zamudio, Sergio; Cruz, Fidel de la; Góngora‐Alfaro, José L.; Armendáriz‐Borunda, Juan; Reyes-Corona, David; Espadas-Álvarez, Armando J.; Flores-Martínez, Yazmin M.; Ayala-Dávila, José; Hernández-Gutiérrez, María Eugenia; Pavón, Lenin; García-Villegas, Refugio; Nadella, Rasajna; Martínez‐Fong, Daniel

doi:10.1186/s12929-015-0166-7

Cited by 63 publications

(59 citation statements)

References 73 publications

(115 reference statements)

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“…It was also shown that the BDNF administration recovers spontaneous motor behavior in the rat model of PD [95]. Combined treatment with a D3 receptor agonist and BDNF in 6-OHDA lesioned rats led to the stabilization of gait parameters, accelerated recovery of motor coordination and balance, and full recovery from muscle rigidity [96].…”

Section: Study In Pd Animal Modelsmentioning

confidence: 97%

“…In the animal models of PD, BDNF brain content was augmented through direct injection of BDNF [88,89], gene transduction by viral vectors [90][91][92][93][94], or delivery via nonviral carriers [95,96] and also via secretion from genetically engineered cells [97][98][99][100][101]. The effects of BDNF treatment were studied in two research schemes in which BDNF was administered before and after the induction of PD.…”

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

“…Similarly controversial results were obtained when induction of parkinsonism by 6-OHDA lesion was followed by BDNF treatment. There seemed to be no recovery of the dopaminergic neurons number in SN [92,95,97,98]. However, Kim et al [92] demonstrated dopaminergic axon regrowth when the Bdnf gene was transduced 6 weeks after the axonal lesion.…”

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

“…Moreover, BDNF treatment of brain slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice was able to restore the impaired synaptic plasticity [102]. In addition, Hernandez-Chan et al [95] observed an increase in the striatal level of DA, while in SN there was no recovery of DA content. Therefore, it seems that even though BDNF does not induce neurogenesis, it exerts a positive influence on the remaining neurons.…”

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

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BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

Pałasz

Wysocka

Gąsiorowska

et al. 2020

IJMS

341

197

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Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson's disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient's brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.

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Section: Study In Pd Animal Modelsmentioning

confidence: 97%

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

Section: Study In Pd Animal Modelsmentioning

confidence: 99%

See 2 more Smart Citations

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

Pałasz

Wysocka

Gąsiorowska

et al. 2020

IJMS

341

197

View full text Add to dashboard Cite

show abstract

“…BDNF is a nerve growth factor produced in different regions in the brain with the highest levels in the hippocampus and cerebral cortex and is essential for neuronal function and survival throughout life (Nagahara and Tuszynski, 2011;Zuccato and Cattaneo, 2009). BDNF is considered as a key target for drug development in neurodegenerative diseases (The BDNF StudyGroup, 1999;Hernandez-Chan et al, 2015;Levivier et al, 1995;Lu et al, 2013;Nagahara et al, 2009;Shruthi et al, 2017;Silva et al, 2015). Intraventricular delivery (Beck et al, 1994;Schäbitz et al, 1997) and intravenous bolus (Müller et al, 2008;Schäbitz et al, 2000Schäbitz et al, , 2007 of BDNF, has been shown to be protective in cerebral ischemia in rat, whereas blockade of endogenous BDNF activity was reported to intensify cerebral ischemia (Larsson et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

14-3-3ζ protein protects against brain ischemia/reperfusion injury and induces BDNF transcription after MCAO in rat

Khalesi¹,

Bandehpour²,

Bigdeli³

et al. 2019

JAB

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Brain ischemia is a leading cause of death and disability worldwide that occurs when blood supply of the brain is disrupted. Brainderived neurotrophic factor (BDNF) is a protective factor in neurodegenerative conditions. Nevertheless, there are some problems when exogenous BDNF is to be used in the clinic. 14-3-3ζ is a pro-survival highly-expressed protein in the brain that protects neurons against death. This study evaluates 14-3-3ζ effects on BDNF transcription at early time point after ischemia and its possible protective effects against ischemia damage. Human 14-3-3ζ protein was purified after expression. Rats were assigned into four groups, including sham, ischemia, and two treatment groups. Stereotaxic cannula implantation was carried out in the right cerebral ventricle. After one week, rats underwent middle cerebral artery occlusion (MCAO) surgery and received 14-3-3ζ (produced in our laboratory or standard form as control) in the middle of ischemia time. At 6 h of reperfusion after ischemia, brain parts containing the hippocampus, the cortex, the piriform cortex-amygdala and the striatum were collected for real time PCR analysis. At 24 h of reperfusion after ischemia, neurological function evaluation and infarction volume measurement were performed. The present study showed that 14-3-3ζ could up-regulate BDNF mRNA at early time point after ischemia in the hippocampus, in the cortex and in the piriform cortex-amygdala and could also improve neurological outcome and reduce infarct volume. It seems that 14-3-3ζ could be a candidate factor for increasing endogenous BDNF in the brain and a potential therapeutic factor against brain ischemia.

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Tetramethylpyrazine induces the release of BDNF from BM‐MSCs through activation of the PI3K/AKT/CREB pathway

Chen

Guo

et al. 2021

Cell Biology International

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Compelling evidences suggest that transplantation of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) can be therapeutically effective for central nervous system (CNS) injuries and neurodegenerative diseases. The therapeutic effect of BM‐MSCs mainly attributes to their differentiation into neuron‐like cells which replace injured and degenerative neurons. Importantly, the neurotrophic factors released from BM‐MSCs can also rescue injured and degenerative neurons, which plays a biologically pivotal role in enhancing neuroregeneration and neurological functional recovery. Tetramethylpyrazine (TMP), the main bioactive ingredient extracted from the traditional Chinese medicinal herb Chuanxiong, has been reported to promote the neuronal differentiation of BM‐MSCs. This study aimed to investigate whether TMP regulates the release of neurotrophic factors from BM‐MSCs. We examined the effect of TMP on brain‐derived neurotrophic factor (BDNF) released from BM‐MSCs and elucidated the underlying molecular mechanism. Our results demonstrated that TMP at concentrations of lower than 200 μM increased the release of BDNF in a dose‐dependent manner. Furthermore, the effect of TMP on increasing the release of BDNF from BM‐MSCs was blocked by inhibiting the phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (AKT)/cAMP‐response element binding protein (CREB) pathway. Therefore, we concluded that TMP could induce the release of BDNF from BM‐MSCs through activation of the PI3K/AKT/CREB pathway, leading to the formation of neuroprotective and proneurogenic microenvironment. These findings suggest that TMP possesses novel therapeutic potential to promote neuroprotection and neurogenesis through improving the neurotrophic ability of BM‐MSCs, which provides a promising nutritional prevention and treatment strategy for CNS injuries and neurodegenerative diseases via the transplantation of TMP‐treated BM‐MSCs.

show abstract

Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson’s disease

Cited by 63 publications

References 73 publications

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

14-3-3ζ protein protects against brain ischemia/reperfusion injury and induces BDNF transcription after MCAO in rat

Tetramethylpyrazine induces the release of BDNF from BM‐MSCs through activation of the PI3K/AKT/CREB pathway

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