Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups
Introduction
Doublecortin (DCX) is a microtubule-associated protein critical for radial and tangential migration of immature neurons in the developing brain (des Portes et al., 1998, Gleeson et al., 1999, Francis et al., 1999, Friocourt et al., 2007). Persistent DCX expression occurs in discrete adult brain regions (Nacher et al., 2001). This adult expression in the subgranular and subventricular zones reflects neurogenic activity giving rise to new granule cells in the hippocampal dentate gyrus and interneurons in the olfactory bulb (Gritti et al., 2002, Couillard-Despres et al., 2005, Gould, 2007). In general, DCX expression in developing neurons declines with cell differentiation and maturation. Therefore, a partial colocalization of DCX with some terminal neuronal markers, e.g., neuron-specific nuclear protein (NeuN), can be detected among a cohort of immature neurons undergoing development (Brown et al., 2003).
Cells concurrently expressing DCX and other immature neuronal markers, e.g., polysialylated neural cell adhesion molecule (PSA-NCAM) and neuron-specific tubulin-III (TuJ1), are reported in layers II/III in mouse/rat piriform cortex (Seki and Arai, 1991, Bonfanti et al., 1992, Nacher et al., 2001), and in primate entorhinal/temporal cortex (Bernier et al., 2002, Tonchev et al., 2003). PSA-NCAM+ cells are also described in rat and human medial prefrontal cortex (Fox et al., 2000, Sairanen et al., 2007, Varea et al., 2007). These cortical cells were classified as mature neurons undergoing structural plasticity (Nacher et al., 2001), and have been lately clarified as immature neurons (Gómez-Climent et al., 2008). Controversy remains as to whether they are born prenatally (Gómez-Climent et al., 2008) or postnatally (Bernier et al., 2002, Pekcec et al., 2006, Shapiro et al., 2007, Shapiro et al., 2008).
Unlike mice and rats, DCX+ cells in adult guinea pigs and rabbits reside in layer II throughout the neocortex in addition to allocortex (Xiong et al., 2008, Luzzati et al., 2008). Therefore, DCX+ cells might have a wide neocortical distribution in higher mammalian species. To explore this possibility, the present study determined DCX+ cells in adult domestic cat, rhesus monkey and human cerebral cortex. DCX+ cells resembling immature and developing neurons were detected in broad cortical areas in these species, with small cells occurring in layers II and upper III and larger ones in all layers. Almost all DCX+ cells co-expressed PSA-NCAM. Relatively larger DCX+ cells with mature-looking morphology colocalized with NeuN, and in part with several terminal markers of interneurons, including γ-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD67), parvalbumin (PV), calbindin (CB), and β-nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) or neuronal isoform of nitric oxide synthase (nNOS). Collectively, DCX+ cells likely represent a wave of immature and maturing neurons undergoing development and differentiation into presumably GABAergic subpopulations. Thus, interneuron development may extend beyond puberty to adulthood in many parts of the cerebral cortex in high mammalian species, and this protracted course of interneuron development may be essential for cortical morphogenesis, plasticity and functionality.
Section snippets
Animal and tissue preparation
Domestic cats aged at 15, 17, and 21 months [young adults, male, mean = 1.5 ± 0.3 year-old (yr-old)] and 42, 55, 59 and 62 months (adults, male, mean = 4.5 ± 0.7 yr-old), weighing 2.1–4.3 kg, were obtained from the animal facility of Hunan Agricultural University (Changsha, Hunan, China). The brains were used to characterize cortical DCX+ cells including a potential age-related decline of the cells in this species (Xiong et al., 2008). Animals were perfused via the ascending aorta with 4%
Distribution of DCX+ cells in young adult cat cortex
In the frontal lobe sections, DCX+ cells and processes were most dense in the subventricular zone lining the anterior horn of the lateral ventricle (Figs. 1A, B). Upon leaving the ventricular wall, labeled profiles arranged in a curved path that paralleled the white matter, instead of entering the overlying cortex (Fig. 1C). Thus, labeling in this region appeared to represent DCX expression in the subventricular zone-rostral migratory stream, as characterized in other species (Nacher et al.,
Discussion
DCX or PSA-NCAM+ cells occur in the piriform and medial prefrontal cortices in small laboratory rodents (Seki and Arai, 1991, Fox et al., 2000, Nacher et al., 2001, Sairanen et al., 2007). These cells are reported or have been noticed in the neocortex as well in larger mammals, including guinea pigs (Xiong et al., 2008, Luzzati et al., 2008), rabbits (Luzzati et al., 2008), cats (Gómez-Climent et al., 2008), monkeys (Bernier et al., 2002, Kornack et al., 2005), and humans (Varea et al., 2007,
Acknowledgments
This study was supported in part by Southern Illinois University School of Medicine and Illinois Department of Public Health (X.X.Y.), Xiangya Medical School (Y.C., X.K.) and National Institute of Health (1R21NS056371 to P.R.P., X.X.Y. and NS054038 to A.W).
References (59)
- et al.
Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study
Neuroscience
(1992) - et al.
Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson's disease?
Neurobiol. Dis.
(2007) Cortical interneurons: from Cajal to 2001
Prog. Brain Res.
(2002)- et al.
Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons
Neuron
(1999) - et al.
Co-localisation of NADPH diaphorase activity and GABA immunoreactivity in local circuit neurones in the medial prefrontal cortex (mPFC) of the rat
Brain Res.
(1995) - et al.
Differential distribution of NADPH-diaphorase histochemistry in human cerebral cortex
Brain Res.
(2005) - et al.
Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons
Neuron
(1999) - et al.
Postnatal development of calcium-binding proteins immunoreactivity (parvalbumin, calbindin, calretinin) in the human entorhinal cortex
J. Chem. Neuroanat.
(2003) - et al.
Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration
Neuroscience
(2004) - et al.
GABAergic neuronal subtypes in the human frontal cortex—development and deficits in schizophrenia
J. Chem. Neuroanat.
(2001)
Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat
Neuroscience
Nitric oxide synthase interneurons in the monkey cerebral cortex are subsets of the somatostatin, neuropeptide Y, and calbindin cells
Brain Res.
Late appearance of parvalbumin-immunoreactive neurons in the rodent cerebral cortex does not follow an ‘inside-out’ sequence
Neurosci. Lett.
Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys
Mol. Cell Neurosci.
PSA-NCAM expression in the human prefrontal cortex
J. Chem. Neuroanat.
Doublecortin-expressing cells are present in layer II across the adult guinea pig cerebral cortex: partial colocalization with mature interneuron markers
Exp. Neurol.
Postnatal development of parvalbumin immunoreactivity in the cerebral cortex of the cat
J. Comp. Neurol.
Postnatal development of calbindin-D28k immunoreactivity in the cerebral cortex of the cat
Anat. Embryol. (Berl).
Four-dimensional migratory coordinates of GABAergic interneurons in the developing mouse cortex
J. Neurosci.
Newly generated neurons in the amygdala and adjoining cortex of adult primates
Proc. Natl. Acad. Sci. U. S. A.
Transient expression of doublecortin during adult neurogenesis
J. Comp. Neurol.
Prenatal development of parvalbumin immunoreactivity in the human striate cortex
Cereb. Cortex
The marginal zone/layer I as a novel niche for neurogenesis and gliogenesis in developing cerebral cortex
J. Neurosci.
Doublecortin expression levels in adult brain reflect neurogenesis
Eur. J. Neurosci.
Postnatal development of pre- and postsynaptic GABA markers at chandelier cell connections with pyramidal neurons in monkey prefrontal cortex
J. Comp. Neurol.
A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome
Cell
Postnatal development of parvalbumin- and GABA transporter-immunoreactive axon terminals in monkey prefrontal cortex
J. Comp. Neurol.
Nitric oxide-producing neurons in the neocortex: morphological and functional relationship with intraparenchymal microvasculature
Cereb. Cortex
Consolidation of passive avoidance learning is associated with transient increases of polysialylated neurons in layer II of the rat medial temporal cortex
J. Neurobiol.
Cited by (0)
- 1
These authors contributed equally to this work.