Dopamine and adult neurogenesis
Andreas Borta and Günter U. HöglingerExperimental Neurology, Philipps University, Marburg, Germany
Address correspondence and reprint requests to Günter U. Höglinger, Experimental Neurology, Philipps University, D-35033 Marburg, Germany. E-mail:
guenter.hoeglinger@med.uni-marburg.de
: BrdU, 5-bromo-2'deoxyuridine; EGFR, epidermal growth factor receptor; NeuN, neuronal nuclear antigen; 6-OHDA, 6-hydroxydopamine; 7-OH-DPAT, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin; PD, Parkinson's disease; PSA-NCAM, polysialic neural cell adhesion molecule; SGZ, subgranular zone; SVZ, subventricular zone; TH, tyrosine hydroxylase.
Abstract
Dopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we approach a highly controversial question: can the adult human brain use neurogenesis to replace the dopaminergic neurones in the substantia nigra that are lost in Parkinson's disease?
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http://www.blackwell-synergy.com/act...9.2006.04241.x
Dopamine and adult neurogenesis
Andreas Borta and Gu¨nter U. Ho¨glinger
Experimental Neurology, Philipps University, Marburg, Germany
Abstract
Dopamine is an important neurotransmitter implicated in the
regulation of mood, motivation and movement. We have reviewed
here recent data suggesting that dopamine, in addition
to being a neurotransmitter, also plays a role in the regulation
of endogenous neurogenesis in the adult mammalian brain. In
addition, we approach a highly controversial question: can the
adult human brain use neurogenesis to replace the dopaminergic
neurones in the substantia nigra that are lost in Parkinson’s
disease?
The recent discovery that the adult mammalian brain has the
potential to generate new neurones and to integrate them into
existing circuits has caused a shift in our understanding of
how the central nervous system functions in health and
disease (Alvarez-Buylla and Lim 2004). It has been consistently
demonstrated, in two distinct areas of the forebrain,
that mature cells in all neural lineages, including neurones,
are generated throughout adulthood. Neuroblasts born in the
adult subventricular zone (SVZ), subadjacent to the ependyma
lining the lateral ventricles, migrate along the rostral
migratory stream to the olfactory bulb, where they become
interneurones. Neuroblasts born in the adult subgranular
zone (SGZ) of the dentate gyrus migrate into the adjacent
granular layer, where they become granular neurones. The
constitutive neurogenesis that occurs in the SVZ and SGZ is
thought to be of functional importance in olfaction, mood
regulation and memory processes (Nilsson et al. 1999;
Santarelli et al. 2003; Enwere et al. 2004; Kempermann
et al. 2004). The factors that govern the generation, migration,
differentiation, integration and survival of new neuroblasts
in the SVZ and SGZ include diffusible molecules such
as neurotransmitters (Hagg 2005; Lledo and Saghatelyan
2005). It is therefore conceivable that an alteration in brain
neurotransmitter levels, as occurs in neurodegenerative
diseases, would affect adult neurogenesis in the SVZ and
SGZ with yet unknown functional consequences. Inversely,
the discovery of adult neurogenesis has raised the hope that
the SVZ and SGZ, or other regions of the adult brain, might
still have the capacity to generate neuroblasts that can replace
the neurones lost through disease.
Parkinson’s disease (PD) has received much attention in
recent years with regard to adult neurogenesis, as the
degenerative process is relatively selective for the dopaminergic
nigrostriatal projection. We have evaluated the published
evidence indicating that (i) dopamine plays a role in
the regulation of constitutive neurogenesis in the adult brain,
and that (ii) adult neurogenesis can repair the damaged
nigrostriatal dopaminergic system.
Dopaminergic control of adult neurogenesis
The neurotransmitter dopamine contributes to the ontogenesis
of the mammalian brain by regulating neural precursor
cell proliferation. Dopamine (Voorn et al. 1988; Ohtani et al.
2003) and its receptors (Lidow and Rakic 1995; Diaz et al.
1997) appear early during embryonic development in the
highly proliferative germinal zones of the brain. Dopamine
receptors are classified as either D1-like (D1 and D5) or D2-
like (D2, D3 and D4), according to structural homologies and
shared second messenger cascades. Dopamine receptors,
particularly of the D3 type, are abundantly expressed during
brain development in the germinative neuroepithelial zones
actively involved in neurogenesis in most basal forebrain
Received August 6, 2006; revised manuscript received September 5,
2006; accepted September 13, 2006.
Address correspondence and reprint requests to Gu¨nter U. Ho¨glinger,
Experimental Neurology, Philipps University, D-35033 Marburg,
Germany. E-mail:
guenter.hoeglinger@med.uni-marburg.de
Abbreviations used: BrdU, 5-bromo-2¢deoxyuridine; EGFR, epidermal
growth factor receptor; NeuN, neuronal nuclear antigen; 6-OHDA,
6-hydroxydopamine; 7-OH-DPAT, 7-hydroxy-N,N-di-n-propyl-2-amiaminotetralin;
PD, Parkinson’s disease; PSA-NCAM, polysialic neural cell
adhesion molecule; SGZ, subgranular zone; SVZ, subventricular zone;
TH, tyrosine hydroxylase.
Keywords: adult neurogenesis, dopamine, Parkinson’s disease,
substantia nigra, subventricular zone.
J. Neurochem. (2007) 100, 587–595.
http://tinyurl.com/2hafca