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Exposure to mission relevant doses of 1 GeV/Nucleon (56)Fe particles leads to
impairment of attentional set-shifting performance in socially mature rats
#MMPMID25029107
Britten RA
; Davis LK
; Jewell JS
; Miller VD
; Hadley MM
; Sanford LD
; Machida M
; Lonart G
Radiat Res
2014[Sep]; 182
(3
): 292-8
PMID25029107
show ga
Previous ground-based experiments have shown that cranial irradiation with
mission relevant (20 cGy) doses of 1 GeV/nucleon (56)Fe particles leads to a
significant impairment in Attentional Set Shifting (ATSET) performance, a measure
of executive function, in juvenile Wistar rats. However, the use of head only
radiation exposure and the biological age of the rats used in that study may not
be pertinent to determine the likelihood that ATSET will be impaired in
Astronauts on deep space flights. In this study we have determined the impact
that whole-body exposure to 10, 15 and 20 cGy of 1 GeV/nucleon (56)Fe particles
had on the ability (at three months post exposure) of socially mature (retired
breeder) Wistar rats to conduct the attentional set-shifting paradigm. The
current study has established that whole-body exposures to 15 and 20 (but not 10)
cGy of 1 GeV/nucleon (56)Fe particles results in the impairment of ATSET in both
juvenile and socially mature rats. However, the exact nature of the impaired
ATSET performance varied depending upon the age of the rats, whether whole-body
versus cranial irradiation was used and the dose of 1 GeV/u (56)Fe received.
Exposure of juvenile rats to 20 cGy of 1 GeV/nucleon (56)Fe particles led to a
decreased ability to perform intra-dimensional shifting (IDS) irrespective of
whether the rats received head only or whole-body exposures. Juvenile rats that
received whole-body exposure also had a reduced ability to habituate to the assay
and to complete intra-dimensional shifting reversal (IDR), whereas juvenile rats
that received head only exposure had a reduced ability to complete compound
discrimination reversal (CDR). Socially mature rats that received whole-body
exposures to 10 cGy of 1 GeV/nucleon (56)Fe particles exhibited no obvious
decline in set-shifting performance; however those exposed to 15 and 20 cGy had a
reduced ability to perform simple discrimination (SD) and compound discrimination
(CD). Exposure to 20 cGy of 1 GeV/nucleon (56)Fe particles also led to a
decreased performance in IDR and to ?25% of rats failing to habituate to the
task. Most of these rats started to dig for the food reward but rapidly (within
15 s) gave up digging, suggesting that they had developed appropriate procedural
memories about food retrieval, but had an inability to maintain attention on the
task. Our preliminary data suggests that whole-body exposure to 20 cGy of 1
GeV/nucleon (56)Fe particles reduced the cholinergic (but not the GABAergic)
readily releasable pool (RRP) in nerve terminals of the basal forebrain from
socially-mature rats. This perturbation of the cholinergic RRP could directly
lead to the loss of CDR and IDR performance, and indirectly [through the
metabolic changes in the medial prefrontal cortex (mPFC)] to the loss of SD and
CD performance. These findings provide the first evidence that attentional
set-shifting performance in socially mature rats is impaired after whole-body
exposure to mission relevant doses (15 and 20 cGy) of 1 GeV/nucleon (56)Fe
particles, and importantly that a dose reduction down to 10 cGy prevents that
impairment. The ability to conduct Discrimination tasks (SD and CD) and reversal
learning (CDR) is reduced after exposure to 15 and 20 cGy of 1 GeV/nucleon (56)Fe
particles, but at 20 cGy there is an additional decrement, ? 25% of rats are
unable to maintain attention to task. These behavioral decrements are associated
with a reduction in the cholinergic RRP within basal forebrain, which has been
shown to play a major role in regulating the activity of the PFC.
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