ROLES OF HDAC INHIBITION IN THE

EFFECTS OF PRENATAL VPA

TREATMENT
 VPA – VALPROIC ACID
Reference 1:
widely used to treat epilepsy, bipolar disorders, and migraine
administration during pregnancy may result in a “fetal valproate syndrome”, which has features similar to
ASD
prenatal VPA exposure  neural damage + behavioral deficits later in life

Online:
Prevent migrance/treat bipolar disorder, epilepsy
(recent work) action as histone deacetylase (HDAC) inhibitor (high dose of VPA)  adjuvant agent in
cancer, HIV therapy, and neurodegenerative disease
TSA
Trichostatin A (TSA) is a potent and specific inhibitor of HDAC class I/II. a member of a larger class of histone deacetylase
inhibitors (HDIs or HDACIs) that have a broad spectrum of epigenetic activities  has some potential as an anti-cancer drug.
can be used to alter gene expression by interfering with the removal of acetyl groups from histones (histone deacetylases,
HDAC)  altering the ability of DNA transcription factors to access the DNA molecules inside chromatin.

HDAC (Histone deacetylases)

are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the
histones to wrap the DNA more tightly.
Its action is opposite to that of histone acetyltransferase.
HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also
includes non-histone proteins.
Is involved in a series of pathways within the living system: Environmental information processing: signal transduction;
Cellular processes: cell growth and death; Human diseases: cancers
PBS:
Phosphate-buffered saline (abbreviated PBS) is a buffer solution (pH ~ 7.4) commonly used in biological research.
isotonic and non-toxic to most cells
maintain a constant Ph  optimal vitality (while saline cannot)

Iba1 antibody (Ionized calcium-binding

adaptor molecule 1)
also called allograft inflammatory factor 1 (AIF 1), is a well-established marker for microglia/macrophages.

DAPI
DAPI (4′,6-diamidino-2-phenylindole) is a blue-fluorescent DNA stain
used as a nuclear counterstain in fluorescence microscopy, flow cytometry, and chromosome staining.
to determine the number of nuclei and to assess gross cell morphology.
showed no ultrastructural changes compared to the appearance of cells not stained with DAPI
Pexidartinib (PLX3397) – a colony
stimulated factor 1 receptor inhibitor
To determine whether microglial reaction contributed to increased pain sensitivity by prenatal VPA exposure
Pexidartinib (PLX3397) is an oral, potent muti-targeted receptor tyrosine kinase inhibitor of CSF-1R, Kit (c-Kit),
and FLT3 with IC50 of 20 nM, 10 nM and 160 nM, respectively.
Pexidartinib (PLX3397) induces apoptosis and necrosis with antitumor activity. Phase 3.
Colony-stimulating factor 1 (CSF1) is a primary regulator of the survival, proliferation, and differentiation of
monocyte/macrophage that sustains the pro-tumorigenic functions of tumor-associated macrophages (TAMs).
 Mac1-saporin – a saporin-conjugated anti-
CD11b antibody
To determine whether spinal microglia responsible for prenatal VPA exposure-induced pain sensitivity 
depleted spinal microglia by intrathecal injection of Mac-1-saporin
a tool for eliminating cells that express Mac-1 (CD11b) receptor in mouse or human; targeted via the antibody
to CR3 (CD11b), eliminated via saporin
 Spinal microglia
Contributor to neuropathic pain (mechanical allodynia) following peripheral nerve damage
Forming and refining neuronal circuitry
Contributing to neuronal plasticity and nociceptive signaling

Cortex
• Prefrontal cortex (layers II/III and V): planning complex cognitive behavior, personality expression, decision making, and moderating
social behaviour.
 behavioral phenotypes
• Somatosensory cortex (layers II/III and IV – V): receiving and processing sensory information from across the body, such as touch,
temperature, and pain.
 social interaction