Transcript Brain growth and development

Brain growth and development
The weight curve of brain is not linear with time but follows a
sigmoid pattern meaning that there is a period of more rapid
growth. This rapid growth is known as the growth spurt and this is
the most vulnerable period where a slightest disturbance may have
a profound effect on overall brain growth and development.
% of increase of growth
Growth Spurt
Time
Species difference:
In some species Growth spurt occurs prenatally (guinea pig, Sheep, Monkey)
whereas it occurs postnatally in other sp. (Human, Rat, Rabbit )
Growth of the Brain
Growth (hyperplasia)
 An increase in the no. of cells until the
adult cellular population is achieved in the
tissue.
Development (hypertrophy)
 Cells are developed into mature functioning
units as a result of deposition of different
cellular constituents (protein, lipid).
 Mature cells differ from immature ones in
 Determined by the genetic make up of
both size and chemical composition.
the individual organs.
Brain growth and development can be divided into 4 phases:
Phase 1: growth proceeds entirely by cell multiplication (Hyperplasia alone), with a
proportional increase in weight, and in protein or DNA or lipid content. At the end of this
phase DNA synthesis is slowed down , gradually but accumulation of other compounds
continues.
Phase 2: It is the combination of both hyperplasia and hyperthophy, in which there is an
increase in cell size and smaller increase in cell number. The rate of DNA accretion slows
down further, but the accumulation of other constituents continues.
Phase 3: DNA synthesis is stopped altogether and cells developed by increasing in size
and continued synthesis and accumulation of proteins and lipids. In this phase only
hypertrophy persists.
Phase 4: Construction of synaptic interneuronal junctions.
Events that occur in 3 Phases:
Phase 1: Organogenesis and neuronal multiplication
Phase 2: Axonal and dendritic growth ; Glial multiplication; Myelination
Phase 3: Growth in size
Phase 4: Synaptogenesis
Prenatal period
Postnatal period
These final structures differentiate during the fetal period of
brain development.
Brain Development
The brain grows at an amazing rate during
development. At times during brain
development, 250,000 neurons are added
every minute!! At birth, almost all the
neurons that the brain will ever have are
present. However, the brain continues to
grow for a few years after birth. By the age of
2 years old, the brain is about 80% of the
adult size.
You may wonder, "How does the brain
continue to grow, if the brain has most of the
neurons it will get when you are born?". The
answer is in glial cells. Glia continues to
divide and multiply. Glia carries out many
important functions for normal brain
function including insulating nerve cells with
myelin. The neurons in the brain also make
many new connections after birth.
Multiplication of Neurons and Gilal cells are two consecutive
process. The former being followed by the later.
Neurogenesis: Neurons originate from the stem cells (Neuroblast) in the
neuroepithelium.
Gliogenesis: In vertebrates both neuro and gliogenesis occurs in
neuroepithelium.
DNA-Phosphate
Birth
Rapid
Gliogenesis
Slow
Rapid
Neurogenesis
Weeks
Only recently has it become generally accepted
that new neurons are added in discrete regions
of the adult mammalian CNS.
• Active neurogenesis occurs throughout the life
in
– Subventricular zone (SVZ) of the lateral ventricle
– Subgranular zone (SGZ) of the dentate gyrus in
the hippocampus
– Other regions are non-neurogenic but
neurogenesis can take place in this regions only
after brain insults
Neurogenesis in the Subventricular Zone
• The forebrain subventricular zone (SVZ) is a prolific source of
neuronal precursors (neural stem cells).
• These neuronal progenitor cells (which give rise to neurons) migrate
to the olfactory bulb by means of a restricted pathway known as the
rostral migratory stream (RMS).
• Once in the core of the olfactory bulb, the cells migrate in a radial pattern
and differentiate into interneurons.
Cell Migration along the RMS
Confocal microscopy images of a cell migrating along the RMS
Neural cell death
Endogenous reasons:
Some Neural cells are subjected to death during
developmental process in CNS. Reasons:
Lac of maintenance from target tissue. Target tissue generally
release one or more neurotrophic factors such as Nerve
growth factors (NGF) which are proved to be essential for the
survival of neurons. In most cases neuronal cells die if they
don’t receive adequate NGF from neuroepithelial cells.
CNS also regulates the total no of neurons by
stimulating neural cell death.
During early periods of development many inaccurate
and aberrant synaptic interconnections are formed in the
nervous tissue which is removed by mediating neural
cell death.
External cause of neural cell death
Stem cell therapy for neurodegeneration
Many common neurological disorders, such as Parkinson’s disease, stroke and multiple sclerosis, are
caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated
successfully from stem cells in culture, fuelling efforts to develop stem-cell-based transplantation therapies
for human patients.
Stem cells would be isolated and transplanted to the diseased brain and spinal cord, either directly or after
predifferentiation/genetic modification in culture to form specific types of neuron and glial cell, or cells
producing neuroprotective molecules.
In strategies relying on stimulation of the patient's own repair mechanisms, endogenous stem
cells would be recruited to areas of the adult brain and spinal cord affected by disease, where
they would produce new neurons and glia (neurogenic and gliogenic areas along lateral
ventricle and central canal are shown in hatched red). Stem cells could provide clinical benefits
by neuronal replacement, remyelination and neuroprotection.
Role of microRNAs during brain development
MicroRNA (miRNA) are a newly recognized class of small, noncoding RNA molecules
that participate in the developmental control of gene expression. The regulation of a set
of highly expressed neural miRNA during mouse and human brain development has
been identified recently.
Putative mRNA targets for developmentally regulated miRNAs
Identifying the miRNA targets
The miRNA and its putative target must be expressed in the same tissue.
Putative targets may undergo posttranscriptional regulation that is coordinated with the miRNA
expression.
Combining this candidate strategy with a search of the NCBI databases revealed several genes
with a high degree of complementarity to developmentally regulated neuronal miRNA
Mechanism of miRNA mediated gene silening
Calcineurin A, an isoform of the calcineurin catalytic subunit, fits these target criteria for
miR- 131. Calcineurin is a major phosphatase of the central nervous system involved in a
variety of neuronal signaling cascades, which plays a critical role in longterm depression. In
humans and rodents, miR-131 demonstrates 19 nt and 18 nt, respectively, out of 21 nt
complementarity to a sequence within the 3 UTR of calcineurin A mRNA. Calcineurin A,
and particularly its expression in developing brain is regulated posttranscriptionally, most
likely at the translational level
mRNA for Id2 (Inhibitor of DNA binding), the protein
antagonizing neuronal differentiation, demonstrates 20 nt
out of 23 nt complementarity to miR-9. So upregulation of
this mir-9 expression occurs during development.
A sequence within DNA helicase SMBP2 transcript is nearly complementary
to miR-103. Mutation of this protein causes mouse neuromuscular degeneration
, a disease similar to human spinal muscular atrophy and linked to miRNAcontaining complex. Otx1, murine homolog of the Drosophila transcription factor
orthodenticle, is necessary for normal corticogenesis, and may represent another
putative target for miR-103.