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Pleiotropic effects of BDNF on the cerebellum and hippocampus: Implications for neurodevelopmental disorders

期刊

NEUROBIOLOGY OF DISEASE
卷 163, 期 -, 页码 -

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ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2021.105606

关键词

Neurotrophins; TrkB receptor; p75 NTR receptor; Postnatal neurodevelopment; Neuroplasticity; Autism spectrum disorder; Attention deficit hyperactivity disorder

资金

  1. Sapienza University [Ateneo 2019_RP11916B88426B8C, H2020_PH120172B92B8494]

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Brain-derived neurotrophic factor (BDNF) is a highly studied neurotrophin in the mammalian brain, crucial for the development of neurons and synaptic plasticity. It is expressed at higher levels in brain areas such as cerebellum and hippocampus. Dysregulation of BDNF expression is associated with neurodevelopmental disorders. Understanding the role of BDNF is important for researching and treating these disorders.
Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the mammalian brain, essential not only to the development of the central nervous system but also to synaptic plasticity. BDNF is present in various brain areas, but highest levels of expression are seen in the cerebellum and hippocampus.After birth, BDNF acts in the cerebellum as a mitogenic and chemotactic factor, stimulating the cerebellar granule cell precursors to proliferate, migrate and maturate, while in the hippocampus BDNF plays a fundamental role in synaptic transmission and plasticity, representing a key regulator for the long-term potentiation, learning and memory. Furthermore, the expression of BDNF is highly regulated and changes of its expression are associated with both physiological and pathological conditions. The purpose of this review is to provide an overview of the current state of knowledge on the BDNF biology and its neurotrophic role in the proper development and functioning of neurons and synapses in two important brain areas of postnatal neurogenesis, the cerebellum and hippocampus.Dysregulation of BDNF expression and signaling, resulting in alterations in neuronal maturation and plasticity in both systems, is a common hallmark of several neurodevelopmental diseases, such as autism spectrum disorder, suggesting that neuronal malfunction present in these disorders is the result of excessive or reduced of BDNF support.We believe that the more the relevance of the pathophysiological actions of BDNF, and its downstream signals, in early postnatal development will be highlighted, the more likely it is that new neuroprotective therapeutic strategies will be identified in the treatment of various neurodevelopmental disorders.

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