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PACAP
1,2 1,3 Randeep Rakwal 1 1 1
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Protective effects of hyaluronan tetrasaccharide on hippocampal
pyramidal neurons in neonatal mouse after hypoxicischemic injury
Takehiko Sunabori, Masato Koike, Yasuo Uchiyama
Hyaluronan HA is one of the major components of the extracellular matrix
that contributes to a wide range of biological functions. The effects of HA differ
mainly depending on the size of the polymers. Here we examined the effect
of HA on hypoxicischemic HI brain injury against neonatal mice with a
lowmolecularsize, HA tetrasaccharide HA4, and largemolecularsize HA
800 kDa. Interestingly, only the HA4treated mice rescued the hippocampal
pyramidal neurons 24hours after HI injury. To explore the underlining pathway,
we focused on the contribution of the Tolllike receptor TLR /NFkB pathway,
since the TLR2 and 4 are also known as receptors for HA. The TLR2 and TLR4
null mice showed protective effects against HI injury, respectively. Moreover, the
transient upregulation of the phosphorylation of p65/RelA, 1hour after HI injury
was canceled when HA4 was administrated. Finally, the expression of the early
inflammatory cytokine, IL1b was also inhibited by HA4 administration. These
results suggest that the protective effect of neurons by HA4 is closely related to
inactivation of the Tolllike receptor/NFkB pathway and reduced expression of
inflammatory cytokines.
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1 1 1 1 2
3 4 1
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5 mg/kg
CA1 CA3, CA4
mRNA
Iba1 5 mg/kg
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The Effects of an mer Peptide of Prosaposin in the Attenuation of
MPP+/MPTP Toxicity in Vitro and in Vivo
1 1 1 1 1 2
1
1
2
Parkinson’s disease PD is a chronic, progressive neurological disorder with
increasing incidence in the aging population. In the present study, we used MPTP
or 1methyl4phenylpyridnium ion MPP+induced dopaminergic neurotoxicity
in C57BL/6J mice or SHSY5Y cells and explore the protective effect and
mechanisms of an 18mer peptide of Prosaposin PS18 on dopaminergic
neurons. PS18 2.0 mg/kg significantly improved behavioral deficits, and
enhanced the survival of THpositive neurons and decreased the activity of
astrocytes in the substantia nigra and striatum in MPTPinduced PD model
mice. In vitro, the CCK8 assay and Hoechst 33258 staining clarified that PS
18 300 ng/ml cotreated with 5mM MPP+ could protect the MMP+induced
nuclear morphological changes and attenuated the cell death induced by MPP+.
In addition, PS18 showed protection from MPP+/MPTPinduced apoptosis in the
SHSY5Y cells and dopaminergic neurons in the PD model mouse via suppression
of JNK/cJun pathway and up regulation of Bcl2 protein, down regulation of
Bax, and inhibition of caspase3.
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GABAA JM
1 2 2 Raj Ladher 3 1
1
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JM1232 GABAA
JM1232
oxygenglucose deprivationOGD
GABAA
GABAA
JM1232
microarray system OGD
OGD
JM1232
JM1232
Real time RTPCR
JM1232
7 6
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