Journal Club - Sanai Et Al Nature 2011

8/2/2019 Journal Club - Sanai Et Al Nature 2011

1/4

JOURNAL CLUB 3

TITLE:

Two migratory streams for postnatal neurogenesis in humans but reduced in numbers

PUBLICATION:

Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-

Verdugo JM, Rowitch DH, Alvarez-Buylla A (2011) Corridors of migrating neurons in the human brain

and their decline during infancy. Nature 478:382-386

NAME OF CANDIDATE: Chethan Reddy

SECTIONS WORDS CHARACTERS

Abstract 50 296

Background and context 336 1878

Neurogeneis decreases dramatically during first 6 months oflife

79 409

Proliferation of immature neurons is associated with an activerostal migratory stream (RMS)

58 323

Medial migratory stream unique to humans 41 222

Discussion 260 1435

Abstract

Sanai et al., in a recent work using neurosurgical resections and autopsy samples, have characterized

postnatal neurogenesis and migration in humans. Neurogenesis and migration decrease dramatically

during the first 6 months of life. They also report the existence of a unique medial migratory stream to

ventromedial prefrontal cortex in humans.


2/4

Background

It has been know for quiet sometime now that neurogenesis occurs in adult brains of several mammals,

including humans. The newly generated neurons have also been shown to migrate and integrate into

functioning circuits.

The major sites of adult neurogenesis are the subventricular zone (SVZ) and the hippocampal formation

(Kukekov et al., 1999). The neurons generated in subventricular zone migrate to olfactory bulb via olfactorytract. In the hippocampus, new neurons are generated in the dentate gyrus and as they mature, they establish

contact with neurons in the CA3 region of hippocampus and contribute to hippocampal plasticity (Toni N,

2011). In addition to these, recent reports also suggest the existence new sites for postnatal neurogenesis,

like the hypothalamus (Miguad M et al., 2010).

Though neurogenesis in adult brains of various species has been well documented, its extent is not well

characterized in humans. In a recent study, Sanai and colleagues have explored the changes in neurogenesis

and migration of neural precursors, with age, in the SVZ in human brain (Sanai et al., 2011). Brain samplesfrom autopsies and surgical resections were examined using techniques of immunohistochemistry with

markers for immature, migratory and proliferating neuronal precursors, in situ hybridization, electron

microscopy and reconstructions from images of serial tissue sections.

Adult subventricular zone and rostral migratory stream

The SVZ, which is a source of neural stem cells, lines the lateral walls of lateral ventricles. In adult humans,

it is mainly composed of four layers (Quiones-Hinojosa et al., 2006). The ependymal cells form the inner

most layer. Second layer is the hypocellular gap, which mainly contains ependymal and astrocytic processes

and is unique to humans. The third layer, astrocyte ribbon, is composed of astrocytes, and is followed by a

transitional zone into brain parenchyma. Neural precursors arising from the SVZ migrate tangentially,

forming a stream of cells called rostral migratory stream (RMS), to reach the olfactory bulb. Upon reaching

the olfactory bulb the cells mature to form local interneurons and intergrate into local circuits (Woong Sun

et al., 2010).

Neurogeneis decreases dramatically during first 6 months of life

During first 6 months of life, the astrocyte ribbon and gap layer are not evident in the SVZ. It is filled with

cells expressing immature glial markers, vimentin and GFAP and immature neuronal markers, DCX and

PSA-NCAM. Expression of proliferation marker, Ki67, and neural stem cell marker, EGFR, were also seen.

The numbers of these cells decrease dramatically during the first 6 months and the zone acquires adult

characteristics like astrocyte ribbon and gap layer by 18 months of age.

Proliferation of immature neurons is associated with an active rostal migratory stream (RMS)

Reconstruction of sagittal and coronal sections of ventral forebrain from first 6 months showed that

subventricular zone contained multiple tributaries of DCX and PSA-NCAM positive cells. These coalesced


3/4


4/4

Bibliography

Bonfanti L, Peretto P (2011) Adult neurogenesis in mammals--a theme with many variations. Eur J

Neurosci. 34:930-950.

Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holts S, van Roon-Mom WM,

Bjrk-Eriksson T, Nordborg C, Frisn J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts

migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243-1249.Frodl T, Reinhold E, Koutsouleris N, Reiser M, Meisenzahl EM (2010) Interaction of childhood stress with

hippocampus and prefrontal cortex volume reduction in major depression. J Psychiatr Res 44:799-807.

Im SH, Yu JH, Park ES, Lee JE, Kim HO, Park KI, Kim GW, Park CI, Cho SR (2010) Induction of striatal

neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic-ischemic brain

injury. Neuroscience 169:259-268.

Kukekov VG, Laywell ED, Suslov O, Davies K, Scheffler B, Thomas LB, O'Brien TF, Kusakabe M,

Steindler DA (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenicregions of adult human brain. Exp Neurol. 156:333-344.

Migaud M, Batailler M, Segura S, Duittoz A, Franceschini I, Pillon D (2010) Emerging new sites for adult

neurogenesis in the mammalian brain: a comparative study between the hypothalamus and the classical

neurogenic zones. Eur J Neurosci 32:2042-2052.

Quiones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S,

Romero-Rodriguez R, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A. (2006) Cellular composition and

cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol

494:415-434.

Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-

Verdugo JM, Rowitch DH, Alvarez-Buylla A (2011) Corridors of migrating neurons in the human brain and

their decline during infancy. Nature 478:382-386

Toni N, Sultan S (2011) Synapse formation on adult-born hippocampal neurons. Eur J Neurosci. 33:1062-

1068.

Woong Sun, Hyun Kim, Younghye Moon (2010) Control of neuronal migration through rostral migratory

stream in mice. Anat Cell Biol 43: 269279.

van Harmelen AL, van Tol MJ, van der Wee NJ, Veltman DJ, Aleman A, Spinhoven P, van Buchem MA,

Zitman FG, Penninx BW, Elzinga BM (2010) Reduced medial prefrontal cortex volume in adults reporting

childhood emotional maltreatment. Biol Psychiatry 68:832-838

Documents

Journal Club - Sanai Et Al Nature 2011