AGE-RELATED DECREASE FOR IN VIVO BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) EXPRESSION IN RESPONSE TO CAVERNOUS NERVE AXOTOMY: A NEUROMODULATORY TARGET FOR ENHANCING NERVE RECOVERY

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

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Identification of brain-derived neurotrophic factor promoter regions mediating tissue-specific, axotomy-, and neuronal activity-induced expression in transgenic mice.

The Journal of Cell Biology ◽

10.1083/jcb.128.1.185 ◽

1995 ◽

Vol 128 (1) ◽

pp. 185-199 ◽

Cited By ~ 87

Author(s):

T Timmusk ◽

U Lendahl ◽

H Funakoshi ◽

E Arenas ◽

H Persson ◽

...

Keyword(s):

Transgenic Mice ◽

Reporter Gene ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Bdnf Gene ◽

Promoter Regions ◽

Bdnf Expression ◽

High Level ◽

Genomic Regions

The structure of rat brain-derived neurotrophic factor (BDNF) gene is complex; four 5' exons are linked to separate promoters and one 3' exon is encoding the BDNF protein. To analyze the relative importance of the regulatory regions in vivo, we have generated transgenic mice with six different promoter constructs of the BDNF gene fused to the chloramphenicol acetyl transferase reporter gene. High level and neuronal expression of the reporter gene, that in many respects recapitulated BDNF gene expression, was achieved by using 9 kb of genomic sequences covering the promoter regions that lie adjacent to each other in the genome (promoters I and II and promoters III and IV, respectively) and by including sequences of BDNF intron-exon splice junctions and 3' untranslated region in the constructs. The genomic regions responsible for the in vivo upregulation of BDNF expression in the axotomized sciatic nerve and in the brain after kainic acid-induced seizures and KCl-induced spreading depression were mapped. These data show that regulation of the different aspects of BDNF expression is controlled by different regions in vivo, and they suggest that these promoter constructs may be useful for targeted expression of heterologous genes to specific regions of the central and peripheral nervous systems in an inducible manner.

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Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression—Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study

Cancers ◽

10.3390/cancers12030688 ◽

2020 ◽

Vol 12 (3) ◽

pp. 688

Author(s):

Adrian Tiron ◽

Irina Ristescu ◽

Paula A. Postu ◽

Crina E. Tiron ◽

Florin Zugun-Eloae ◽

...

Keyword(s):

Cancer Progression ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Long Term Effects ◽

Short Term ◽

Bdnf Expression ◽

In Vivo Models

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1α, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.

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Restoration of Long-Term Potentiation in Middle-Aged Hippocampus After Induction of Brain-Derived Neurotrophic Factor

Journal of Neurophysiology ◽

10.1152/jn.00336.2006 ◽

2006 ◽

Vol 96 (2) ◽

pp. 677-685 ◽

Cited By ~ 98

Author(s):

Christopher S. Rex ◽

Julie C. Lauterborn ◽

Ching-Yi Lin ◽

Eniko A. Kramár ◽

Gary A. Rogers ◽

...

Keyword(s):

Neurotrophic Factor ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Brain Derived Neurotrophic Factor ◽

Aged Rats ◽

Middle Aged ◽

Age Related ◽

Term Potentiation

Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.

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Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

Current Alzheimer Research ◽

10.2174/1567205016666190408123947 ◽

2019 ◽

Vol 16 (4) ◽

pp. 344-352

Author(s):

Radhika Khosla ◽

Avijit Banik ◽

Sushant Kaushal ◽

Priya Battu ◽

Deepti Gupta ◽

...

Keyword(s):

Neurodegenerative Disorders ◽

Neurotrophic Factor ◽

Animal Studies ◽

Neurodegenerative Disorder ◽

Indirect Evidence ◽

Brain Derived Neurotrophic Factor ◽

Common Disease ◽

Inverse Association ◽

Bdnf Expression ◽

Strong Inverse Association

Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer’s and Parkinson’s disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.

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The GSK-3β/β-Catenin Signaling–Mediated Brain–Derived Neurotrophic Factor Pathway Is Involved in Aluminum-Induced Impairment of Hippocampal LTP In Vivo

Biological Trace Element Research ◽

10.1007/s12011-021-02582-9 ◽

2021 ◽

Author(s):

Huifang Zhang ◽

Yingchao Han ◽

Ling Zhang ◽

Xiaofang Jia ◽

Qiao Niu

Keyword(s):

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Gsk 3Β

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P1-031: Age-related cerebral changes of brain-derived neurotrophic factor in a model of Alzheimer's disease in APP23 transgenic mice

Alzheimer s & Dementia ◽

10.1016/j.jalz.2006.05.406 ◽

2006 ◽

Vol 2 ◽

pp. S103-S103

Author(s):

Olaf Schulte-Herbrüggen ◽

Uwe Deicke ◽

Uwe Otten ◽

Dorothee Abramowski ◽

Matthias Staufenbiel ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Model Of Alzheimer’S Disease ◽

Age Related

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Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

Clinical Science ◽

10.1042/cs20160009 ◽

2016 ◽

Vol 131 (2) ◽

pp. 123-138 ◽

Cited By ~ 56

Author(s):

Veronica Begni ◽

Marco Andrea Riva ◽

Annamaria Cattaneo

Keyword(s):

Synaptic Plasticity ◽

Stress Response ◽

Neurotrophic Factor ◽

Molecular Mechanisms ◽

Depressive Disorders ◽

Brain Derived Neurotrophic Factor ◽

Mitogen Activated Protein Kinase ◽

Bdnf Expression ◽

Pathological Conditions ◽

Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

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