Page 129 - NNS 2014 Program & Abstract Book

circuitry. Newly-born granule cells undergo a relatively stereotypical
development, where they remain closely association with the GFAP-
expressing, radial glial-like progenitor-cell mothers. These radial glial-
like cells provide a scaffold for the newborn neurons to integrate into
the existing granule cell circuitry. Previous studies have demonstrated
that alterations to this relationship promote a pro-epileptogenic, recur-
rent excitatory circuitry. Thus, for the current study, we examined
neurogenesis in the hippocampus of mice that received a fluid per-
cussion traumatic brain injury (TBI) that was previously shown to result
in increased seizure susceptibility. The results show an increase in
hippocampal neurogenesis between 1 and 7 days after TBI. In addition,
after TBI, newborn granule cells exhibited hilar basal dendrite
sprouting, an anatomical hallmark of recurrent excitatory circuit
formation. Moreover, the hilar basal dendrites were observed to
grow along an ectopic glial scaffold. Finally, examination of neu-
rogenesis within the RMS also revealed a TBI-induced increase in
cell proliferation along this pathway. Future studies are needed to
determine the functional significance of these TBI-induced neuro-
genic alterations.
Key words
basal dendrites, hilar basal dendrites, hippocampus, neurogenesis,
rostral migratory stream, subventricular zone
C3-23
EFFECT OF TRAUMATIC BRAIN INJURY ON WILD-TYPE
ALPHA-SYNUCLEIN EXPRESSION IN RAT HIPPOCAMPUS
Yan, H.Q.1,2, Carlson, S.1,2, Li, Y.1,2, Henchir, J.1,2, Ma, X.1,2, Dixon,
C.E.1,2
1Neurosurgery, University of Pittsburgh, Pittsburgh, USA
2VA Pittsburgh Healthcare System, Pittsburgh, USA
Synucleins (Syn), a family of synaptic proteins, includes alpha-sy-
nuclein (a-Syn), which plays a pivotal role in Parkinson’s disease and
related neurodegenerative diseases. The native function of a -synuclein
is not completely understood, but is thought to involve regulation of
synaptic vesicle trafficking. While the pathological forms of a -syn are
considered to be the primary targets of TBI-associated neurodegen-
eration, disruption of the native function of a-Syn may contribute to
pathology by diminishing synaptic function. Thus, the goal of the
project was to examine the effects of TBI produced on wild-type a-
Syn expression at 6 hours to 8 weeks post injury. Male Sprague-
Dawley rats were anesthetized and surgically prepared for controlled
cortical impact (CCI) injury (4 m/sec, 2.6 mm) or sham surgery. Rats
were randomly assigned TBI or sham surgery and sacrificed for
Western blot analysis and immunofluorescence double labeling assay
by using commercial available antibodies. Semiquantitative mea-
surements of the hippocampal tissues from rats sacrificed at 6 hour, 1
day, 1 week, 2 weeks, 4 weeks, and 8 weeks after injury or sham
operation (N = 6 per group per time point) that were assessed using
Western blot analysis show that expression of a-Syn are decreased
ipsilaterally from 6 h to 8 weeks in the hippocampus (P < 0.05).
Double-label immunofluorescent staining sacrificed at 1 week after
TBI or sham for a -Syn, neuron marker NeuN and astrocytes marker
glial fibrillary acidic protein (GFAP) confirmed the Western blot
findings. The increased expression of GFAP represents concomitant
astrogliosis. This study suggests that wild-type a-Syn protein in the
ipsilateral hippocampus is decreased after TBI compared to the sham
controls. Additional work is required to determine if this represents a
shift toward more cytotoxic forms of a-Syn or a reorganization of
synaptic vesicle trafficking after TBI. Support: Veterans Administra-
tion, the Pittsburgh Foundation, NIH-NS40125, NIH-NS060672.
Key words
alpha-synuclein, immunofluorescence, traumatic brain injury, Western
blot
C3-24
AUGMENTED FEAR BEHAVIOR FOLLOWING TRAU-
MATIC BRAIN INJURY IS ACCOMPANIED BY INCREASED
CORTICAL GABA
Schneider, B.L.3, Ghoddoussi, F.4, Charlton, J.1, Kohler, R.3, Perrine,
S.A.3, Conti, A.C.1–3
1John D. Dingell VA Medical Center, Detroit, USA
2Neurosurgery Department, Wayne State University, Detroit, USA
3Psychiatry and Behavioral Neurosciences Department, Wayne State
University, Detroit, USA
4Anesthesiology Department, Wayne State University, Detroit, USA
Individuals with mild traumatic brain injury (mTBI) often develop
changes in affect including anxiety, depression, or symptoms resem-
bling posttraumatic stress disorder (PTSD). It is unclear how mTBI
results in PTSD-like symptoms, although studies suggest decreased
prefrontal cortex (PFC) activation alters responses in downstream
regions associated with fear learning, such as amygdala and hippo-
campus. To investigate this, we used a mouse model of mTBI and
examined the effects of mild injury on fear behaviors and associated
neurochemical alterations in the PFC.
Anesthetized male C57BL/6 mice (10–12 wks) impacted over the
sagittal suture of the intact skull or exposed to surgery alone (sham
controls). To assess levels of excitatory and inhibitory neurochemi-
cals, PFC was harvested for proton magnetic resonance spectroscopy
analysis ex vivo at 11.7 T at 8 d post-injury. A second cohort was used
to assess fear response (freezing) to contextual fear conditioning (FC)
at 14 d post-injury. FC consisted of 5 phases: habituation, acquisition,
extinction, reinstatement, and extinction recall of conditioned fear.
Mice with mTBI demonstrated significantly increased freezing
during acquisition and extinction compared to controls. No differ-
ences in baseline freezing or freezing during reinstatement or ex-
tinction recall after reinstatement. GABA levels were significantly
increased in the PFC of mTBI mice compared to controls.
The increased acquisition and slower extinction of conditioned fear
observed in mTBI mice resemble features of FC reported in PTSD and
mTBI patients. Increased GABA in the PFC may reflect an increase in
inhibitory activity and support the hypothesis that mTBI-induced PFC
hypoactivity limits top-down control over subcortical areas involved
in FC; thereby increasing susceptibility to affective disorders.
Therefore, this model of mTBI-induced changes in PFC may give
valuable insight into mechanisms involved in developing affective
alterations following mTBI.
Key words
affective disorders, animal model, neuroplasticity, traumatic brain
injury
C3-25
ASTROCYTE-MEDIATED CIRCUIT REORGANIZATION:
EVIDENCE FROM SYNAPTOGENIC EXPRESSION AFTER
EXPERIMENTAL DIFFUSE TRAUMATIC BRAIN INJURY
Evilsizor, M.N.1,2, Korp, K.E.1,2, Adelson, P.D.1,2, Lifshitz, J.1–3,
Thomas, T.C.1–3
A-97