Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Sep;54(6):578-89.
doi: 10.1002/dev.20546. Epub 2011 Mar 22.

BDNF control of adult SVZ neurogenesis

Kevin G Bath  1 , Michael R Akins, Francis S Lee
Affiliations
Review

BDNF control of adult SVZ neurogenesis

Kevin G Bath et al. Dev Psychobiol. 2012 Sep.

Abstract

The sensory processing of odorants is a dynamic process that requires plasticity at multiple levels. In the olfactory bulb (OB), inhibitory interneurons undergo lifelong replacement through a process known as adult neurogenesis. These newly born cells are incorporated in a learning-dependent fashion, a process which has led some to suggest this as a primary mechanism through which the OB retains a high degree of plasticity throughout life. A continued focus of researchers in this field has been to understand the molecular mechanisms controlling adult subventricular zone (SVZ) neurogenesis and the innate functional role of these cells. Brain-derived neurotrophic factor (BDNF) has been identified as a strong candidate molecule regulating adult OB neurogenesis. We review what is known regarding the functional role of newly born cells, highlight the role of BDNF in this process, and describe preliminary findings from our lab implicating BDNF in the process of selecting of newly born cells for survival.

PubMed Disclaimer

Figures

Figure 1
Figure 1. BDNF and its receptors
Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family of polypeptide growth factors. BDNF is synthesized from a 32 kDa precursor protein known as ProBDNF, which preferentially binds to the p75NTR neurotrophin receptor (Lee et al., 2001; Teng et al., 2005). ProBDNF binding to p75NTR and ensuing signaling has been linked with the induction of cell death and suppression of cell cycling in a variety of cellular populations. ProBDNF is cleaved to produce a mature 14 kDa form of BDNF which binds preferentially to the tropomysin related kinase receptor, TrkB (Chao, 2003). Mature BDNF signaling depends upon which of the 4 distinct isoforms of TrkB it binds to. There are two full-length forms of TrkB (TrkB.FL) which differ in a short amino acid insert on the extracellular domain, but both contain an active kinase domain with multiple phosphorylation sites. Activation of the full-length form of TrkB is thought to promote cellular differentiation, survival, neurite outgrowth, and synaptic plasticity (Reichardt, 2006). In addition, two truncated forms of TrkB have been identified, TrkB.T1 and TrkB.T2 which both lack the intracellular kinase domain (Stoilov et al., 2002; Reichardt, 2006). The truncated forms of TrkB are largely thought to function as endogenous dominant negatives (Eide et al., 1996; Haapasalo et al., 2001). However, recent work by Mattson and colleagues have identified a potential role for truncated TrkB in signaling via trans-activation of a G-protein coupled receptor (Cheng et al., 2007). In this model, truncated TrkB is though to function in the process of gliogenesis.
Figure 2
Figure 2. Developmental Expression of Neurotrophins
The expression of BDNF is dynamically regulated across development. In the OB of the mouse, BDNF levels are low during prenatal development and increase over the first weeks of life, peaking during adolescence and then declining across the remainder of life. Expression of p75NTR also changes dramatically over the lifespan. p75NTR is highly expressed prenatally and is then rapidly suppressed in most brain regions postnatally. The full-length form of the TrkB receptor appears be stably expressed across the lifespan, while TrkB.T1 expression appears to mirror that of BDNF, peaking during adolescence (unpublished data). The developmental peak in BDNF expression, occurs following the embryonic and early postnatal organization of the OB. This peak appears to correlate well with development of a proper RMS and the onset of adult-like neurogenesis.
Figure 3
Figure 3. Cell-specific deletion of BDNF impacts rates of OB neurogenesis
Histograms depicting the effects of selective genetic deletion of BDNF from A) Nestin-positive, B) Dlx5/6-positive, or C) CamKIIa-positive cells on rates of cell survival within the adult mouse OB. All groups were compared with Cre-positive mice that did not contain LoxP sites flanking the bdnf gene. Nestin-Cre BDNF LoxP groups were small (n=2) due to high postnatal mortality of this line. * p < 0.05.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alonso M, Viollet C, Gabellec MM, Meas-Yedid V, Olivo-Marin JC, Lledo PM. Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci. 2006;26:10508–10513. - PMC - PubMed
    1. Altman J. Are new neurons formed in the brains of adult mammals? Science. 1962;135:1127–1128. - PubMed
    1. Altman J. Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol. 1969;137:433–457. - PubMed
    1. Altman J, Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. JComp Neurol. 1965;124:319–335. - PubMed
    1. Bagley JA, Belluscio L. Dynamic imaging reveals that brain-derived neurotrophic factor can independently regulate motility and direction of neuroblasts within the rostral migratory stream. Neuroscience. 2010;169:1449–1461. - PMC - PubMed

Publication types

Substances