Brain Derived Neurotrophic Factor: A novel neurotrophin involved in psychiatric and neurological disorders

Balaratnasingam, Sivasankaran; Janča, Aleksandar

doi:10.1016/j.pharmthera.2012.01.006

Cited by 120 publications

(84 citation statements)

References 103 publications

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“…Interestingly, a number of reports linked BDNF neurotransmission in the neuropathophysiology of psychiatric disorders in general (Balaratnasingam and Janca, 2012) and depression in particular (Duman and Monteggia, 2006). Unfortunately, the molecular mechanism by which BDNF may contribute to the pro-depressant effect of social stress is still not well understood.…”

Section: Discussionmentioning

confidence: 99%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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Summary Several lines of evidences suggest that the brain-derived neutrophic factor (BDNF) is implicated in the pathophysiology of depression. However, the molecular mechanisms are not fully understood. In the current study we aimed to investigate how genetic modulation of BDNF in the hippocampus using microRNa124a (miR124a)-expressing lentiviral vectors (LV) might affect depression-like behavior in adult rats. For this purpose, we assessed the expression level of miR124a and its direct target BDNF in the hippocampus and the cortex after 21-days exposure to social defeat stress. Results demonstrated that miR124a was up-regulated in the hippocampus but not in the cortex. In contrast, and as expected, BDNF transcripts were down-regulated. In a different set of experiments, male Wistar rats received bilateral intra-hippocampal or intracortical infusions of BDNF-and miR124a-expressing lentiviral vectors and depression-like behavior was assessed after 21-days social defeat stress using the novelty suppressed feeding, the sucrose preference and the forced swim tests. The results indicated that miR124a overexpression exacerbated depression-like behavior. However, an anti-depressant like effect was observed when BDNF or miR124a-silencers (siR124a) were injected into the hippocampus. Importantly, when expressed into the cortex, LV-miR124a, LV-siR124a and LV-BDNF had no effect on depression. Our findings indicate that hippocampal miR124a and its direct target BDNF play an important role in depression-like behavior. Taken together, the current results reveal, for the first time, a potential molecular regulation of miR124a on BDNF, and the pronounced behavioral consequences of this regulation shed light on the mechanisms underlying BDNF anti-depressant potential. #

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Section: Discussionmentioning

confidence: 99%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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“…An important contributor driving neural adaptation and antidepressant-like effects is brain derived neurotrophic factor (BDNF) (Castren and Rantamaki, 2010). BDNF protects neurons from injury, at least in part, by inhibiting apoptosis and by stimulating neurite sprouting and neuronal reorganization (Balaratnasingam and Janca, 2012). BDNF is formed from its precursor, pro-BDNF, and both pro-BDNF and mature BDNF levels are altered in animal models of depression and in humans with this mood disorder (Castren and Rantamaki, 2010, Polyakova et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice

et al. 2016

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Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals, however its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan may serve as a safer alternative based on pharmacodynamic similarities to ketamine. In this proof of concept study, behavioral and biochemical analyses were undertaken to evaluate the potential involvement of brain derived neurotrophic factor (BDNF) in the antidepressant-like effects of dextromethorphan in mice, with comparisons to ketamine and imipramine. Male Swiss, Webster mice were injected with dextromethorphan, ketamine or imipramine and their behaviors evaluated in the forced swim test (FST) and open field test. Western blots were used to measure brain derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, protein expression in the hippocampus and frontal cortex of these mice. Our results show dextromethorphan and imipramine each reduced immobility time in the FST without affecting locomotor activity, whereas ketamine reduced immobility time and increased locomotor activity. Ketamine also rapidly (within 40 min) increased pro-BDNF expression in an AMPA receptor-dependent manner in the hippocampus, while DM and imipramine did not alter pro-BDNF or BDNF levels in either the hippocampus or frontal cortex within this timeframe. These data demonstrate that dextromethorphan shares some features with both ketamine and imipramine. Additional studies looking at dextromethorphan may aid in the development of more rapid, safe, and efficacious antidepressant treatment.

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“…Studies have confirmed BDNF as being implicated in a wide spectrum of neurological and neurodegenerative diseases, such as mood disorders and neurological disorders (Autry and Monteggia, 2012;Balaratnasingam and Janca, 2012;Boulle et al, 2012;Duman, 2004;Lu et al, 2013). Furthermore, it has been shown in rodent models that BDNF expression is sensitive to early environmental challenges and is reduced by a variety of adverse influences known to be risk factors for neurodevelopmental disorders such as maternal nutrient deficiency (Sable et al, 2011(Sable et al, , 2014, prenatal alcohol exposure (Caldwell et al, 2008;Feng et al, 2005;Maier et al, 1999) and early life stress (Roceri et al, 2002).…”

Section: Bdnf As Therapeuticmentioning

confidence: 98%

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders

Hill

2015

Neurochemistry International

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Brain Derived Neurotrophic Factor: A novel neurotrophin involved in psychiatric and neurological disorders

Cited by 120 publications

References 103 publications

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders

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