![]() On the other hand, BDNF in its mature form binds specifically to tyrosine kinase receptors (TrkB) and promotes cell survival ( Volosin et al., 2006), facilitates LTP and increases spine complexity ( McAllister et al., 1999 Zagrebelsky et al., 2005). ProBDNF preferentially binds p75 NTR receptor, which facilitates LTD ( Woo et al., 2005) and induces apoptosis ( Friedman, 2010). The proBDNF form is secreted under both pathological and non-pathological conditions ( Barker, 2009). Interestingly, BDNF and proBDNF are associated with opposing effects on cellular function, which gives BDNF protein function an additional level of complexity. BDNF is released in an activity dependent manner as a mixture of pro and mature BDNF ( Pang et al., 2004). The regulation of each transcript is controlled and/or modulated by factors like neuronal activity ( Metsis et al., 1993), exercise ( Oliff et al., 1998), antidepressants ( Russo-Neustadt et al., 2004), stress ( Lauterborn et al., 1998), and hormones such as estrogens ( Singh et al., 1995).īrain derived neurotrophic factor is synthesized as the precursor proBDNF, that can be stored in either dendrites or axons ( Lessmann et al., 2003), and undergoes cleavage intra or extracellularly ( Lee et al., 2001 Mowla et al., 2001) to produce a mature BDNF protein. Lower levels of BDNF have been detected in organs such as the liver, heart, lung, among others ( Ernfors et al., 1990 Maisonpierre et al., 1991). Regarding the pattern of expression of BDNF in the brain, high levels of this molecule have been detected in the hippocampus, amygdala, cerebellum and cerebral cortex in both rodents and humans, with the highest levels found in hippocampal neurons ( Hofer et al., 1990 Timmusk et al., 1993). Additionally, the expression of specific BDNF exons can be regulated by epigenetic mechanisms ( Lubin et al., 2008), suggesting that environmental experiences dynamically influence mature BDNF levels. BDNF splicing has been described for several species, including humans ( Liu et al., 2005), mice ( Hayes et al., 1997), and rats ( Timmusk et al., 1993). ![]() There have been identified at least four BDNF promoters in the rat ( Timmusk et al., 1993), each one driving the transcription of mRNAs that contain one of the 8 non-coding exons spliced to the common 30 coding exons, which produce an heterogeneous population of BDNF transcripts. Transcription is controlled by multiple promoters that determine activity-dependent and tissue specific expression ( Timmusk et al., 1993 Chen et al., 2003). The presence of a complex multi-level regulation demonstrates the importance and diversity of BDNF functions. The expression of BDNF is regulated during transcription and translation, and also by post-translational modifications. In the adult brain, BDNF also maintains high expression levels and regulates both excitatory and inhibitory synaptic transmission and activity-dependent plasticity ( Tyler et al., 2002 Wardle and Poo, 2003). The brain derived neurotrophic factor (BDNF) belongs to a family of neurotrophins that have a crucial role in survival and differentiation of neuronal populations during development ( Huang and Reichardt, 2001). We propose that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases because of its disregulation common to many pathological conditions, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.īDNF: A Dynamically Regulated Player in Synaptic Plasticity and Memory In this review, we will describe studies from rodents and humans to bring together research on how BDNF expression is regulated, how this expression changes in the pathological brain and also exciting work on how interventions known to enhance this neurotrophin could have clinical relevance. Some interventions like exercise or antidepressant administration enhance the expression of BDNF in normal and pathological conditions. Changes in BDNF expression are associated with both normal and pathological aging and also psychiatric disease, in particular in structures important for memory processes such as the hippocampus and parahippocampal areas. The expression of BDNF is highly regulated, and can lead to great variability in BDNF levels in healthy subjects. Laboratory of Memory Research and Molecular Cognition, Institute for Cognitive and Translational Neuroscience, Instituto de Neurología Cognitiva, CONICET, Universidad Favaloro, Buenos Aires, Argentinaīrain Derived Neurotrophic Factor (BDNF) is a key molecule involved in plastic changes related to learning and memory.Magdalena Miranda, Juan Facundo Morici, María Belén Zanoni and Pedro Bekinschtein *
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