Cell Biology of BDNF and its Relevance to Schizophrenia

Lu, Bai; Martinowich, Keri

doi:10.1002/9780470751251.ch10

Cited by 82 publications

(63 citation statements)

References 52 publications

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“…Changes in BDNF expression in the inner ear that may have a genetic, epigenetic, or environmental origin may thus have to be reconsidered in the context of these findings for their consequences for hearing. Accordingly, a gradual age-related loss of BDNF in the cochlea, as previously shown to occur in the third life span in rats and gerbils , or altered BDNF levels in psychiatric and neurodegenerative disorders (Lu and Martinowich, 2008;Krishnan and Nestler, 2010;Pardon, 2010), may be discussed in the context of altered loudness perception that has been described in these diseases (Frisina, 2009;Aznar and Knudsen, 2011). Finally, the current ideas to propose BDNF as a promising future therapeutic for hearing deficits (Pettingill et al, 2011) may be revisited in the context of the present study.…”

Section: Ko Micementioning

confidence: 79%

“…In the adult CNS it displays an important role for memory and cognitive functions (Thoenen, 2000;Bramham and Messaoudi, 2005;Minichiello, 2009), as well as for the development and maintenance of mature dendritic complexity and spine density in selected brain centers (Rauskolb et al, 2010). On the other hand, unbalanced regulation of BDNF can also be harmful as discussed in the context of neuropathic pain (Biggs et al, 2010) or in psychiatric and neurodegenerative disorders (Hu and Russek, 2008;Lu and Martinowich, 2008;Krishnan and Nestler, 2010;Pardon, 2010;Aznar and Knudsen, 2011). So far it is elusive whether either of these predicted roles of BDNF is relevant for the mature auditory system because constitutive BDNF KO mice, in which a role of BDNF for survival of neonatal vestibular neurons has been described (Ernfors et al, 1995;Fritzsch et al, 2004), die too early to assess the role of BDNF in the mature auditory system.…”

Section: Introductionmentioning

confidence: 99%

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Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss

Zuccotti¹,

Kuhn²,

Johnson³

et al. 2012

Journal of Neuroscience

120

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The precision of sound information transmitted to the brain depends on the transfer characteristics of the inner hair cell (IHC) ribbon synapse and its multiple contacting auditory fibers. We found that brain derived neurotrophic factor (BDNF) differentially influences IHC characteristics in the intact and injured cochlea. Using conditional knock-out mice (BDNF Pax2 KO) we found that resting membrane potentials, membrane capacitance and resting linear leak conductance of adult BDNF Pax2 KO IHCs showed a normal maturation. Likewise, in BDNF Pax2 KO membrane capacitance (⌬C m ) as a function of inward calcium current (I Ca ) follows the linear relationship typical for normal adult IHCs. In contrast the maximal ⌬C m , but not the maximal size of the calcium current, was significantly reduced by 45% in basal but not in apical cochlear turns in BDNF Pax2 KO IHCs. Maximal ⌬C m correlated with a loss of IHC ribbons in these cochlear turns and a reduced activity of the auditory nerve (auditory brainstem response wave I). Remarkably, a noise-induced loss of IHC ribbons, followed by reduced activity of the auditory nerve and reduced centrally generated wave II and III observed in control mice, was prevented in equally noise-exposed BDNF Pax2 KO mice. Data suggest that BDNF expressed in the cochlea is essential for maintenance of adult IHC transmitter release sites and that BDNF upholds opposing afferents in high-frequency turns and scales them down following noise exposure.

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Section: Ko Micementioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss

Zuccotti¹,

Kuhn²,

Johnson³

et al. 2012

Journal of Neuroscience

120

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“…BDNF has in turn been implicated in bipolar disorder [18,[55][56][57][58] and schizophrenia [59,60].…”

Section: Discussionmentioning

confidence: 99%

Hyperactivity and Enhanced Curiosity of Mice Expressing PKB/SGK-resistant Glycogen Synthase Kinase-3 (GSK-3)

Ackermann

Kempe²,

Läng³

et al. 2010

Cell Physiol Biochem

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Background: Mounting evidence suggests that bipolar disorder symptoms could be favorably influenced by modification of glycogen synthase kinase-3 (GSK-3) activity. Specifically, the well known antimanic and mood stabilizing medications lithium, valproate, olanzapine and clozapine have been shown to inhibit GSK-3 activity. GSK-3 is phosphorylated and thus inhibited by protein kinase B (PKB/Akt) and serum and glucocorticoid inducible kinase (SGK) isoforms. The present study explored, whether PKB/SGK-dependent GSK-3 regulation influences the behavior of mice. Methods: Gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK-3Α, Β (gsk-3^KI) were compared to corresponding wild type mice (gsk-3^WT). The mice were analyzed by open-field, light-dark (LD-) box, O-maze, emergence test, object exploration test and forced swimming test (FST). Results: In open-field, LD-box and O-maze, gsk-3^KI mice displayed a hyperactive and more curious phenotype when compared to wild type mice. Speed and total distance moved as well as rearings were significantly increased in gsk-3^KI compared to gsk-3^WT mice. In the O-maze, gsk-3^KI mice tended to travel a larger distance in the open, unprotected area thangsk-3^WT mice, and performed significantly more unprotected head dips suggesting decreased anxiety behavior. In the forced swimming test, the immobility time was significantly decreased in gsk-3^KI mice indicating a phenotype less prone to depression. Moreover, gsk-3^KImice were less sensitive to the application of chronic mild stress and showed a decreased HPA axis activity. Conclusions: The present observations disclose a significant role of PKB/SGK-dependent regulation of GSK-3 in the control of activity, anxiety and proneness to depression. Accordingly, mice expressing SGK/PKB resistant GSK-3 may be a valuable model of hyperactivity and mania.

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“…Despite these findings, the underlying neurobiology mediating the effect of this particular polymorphism on brain functioning and its interaction with other genetic factors are still not well understood. However, it seems evident that inappropriate or inadequate neurotrophic support during brain development could underlie structural and functional disorganization of neural and synaptic networks (Lu and Martinowich, 2008), leading to an impaired brain with, probably, a decreased ability to make the normal and necessary adaptive changes according to the inputs received.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

Castro-Català

Nierop

Barrantes‐Vidal

et al. 2016

Journal of Psychiatric Research

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Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n=808, sample 1) and a female twin sample (n=621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field.

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Cell Biology of BDNF and its Relevance to Schizophrenia

Cited by 82 publications

References 52 publications

Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss

Lack of Brain-Derived Neurotrophic Factor Hampers Inner Hair Cell Synapse Physiology, But Protects against Noise-Induced Hearing Loss

Hyperactivity and Enhanced Curiosity of Mice Expressing PKB/SGK-resistant Glycogen Synthase Kinase-3 (GSK-3)

Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

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