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Advanced Neurology Voluntary running effects in PTEN knockout mouse

mice . Locomotion was also evaluated in the arena of the incidence of autism spectrum disorder is about 3 – 4 times
[55]
open field (Figure 2B). higher in boys than in girls [63,64] . Similar to social behavior
In behavioral tasks, such as the arena of the open field data, 10 days of physical exercise did not induce any
(Figure 3A), anxiety-like behavior can also be evaluated, changes in fear memory. Therefore, the mice remembered
alongside locomotion. For PTEN knockout male mice, an that the dark side of the chamber was associated with foot
increase in anxiety-like behavior and locomotor activity shock.
has been previously described . However, for females, no According to previous studies in the literature,
[56]
difference in the time spent in the center of the apparatus physical exercise has been shown to be related to synaptic
was observed between PTEN and PTEN mice . Our transmission by positively modulating the NMDA
[54]
+/-
+/+
results showed that all the groups of mice spent more time receptor subunits. This modulation includes an increased
in the periphery of the open field (Figure 3A) and in the expression of these subunits but also their phosphorylated
closed arms of elevated plus maze apparatus (Figure 3B), forms . As we did not observe any effects of physical
[30]
indicating anxiogenic-like behavior, regardless of physical exercise on animal behavior, we also did not observe
exercise and animal genotype. any alterations in terms of NMDA receptor subunit
In the sociability task, we observed no difference modulation, except for the fact that HT mice showed an
among groups (Figure 4A). However, we did not find that increase in NR1 expression (Figure 6E). Interestingly, this
social recognition memory was preserved in sedentary effect of increased NR1 expression in HT mice aligns with
WT animals, while HT mice exhibited impaired social the findings from experiments where PTEN expression was
[65]
recognition memory (Figure 4B). This pattern of deleted using siRNA . This increase in NR1 expression
abnormalities in social behavior resembles what is usually observed in HT mice could potentially contribute to
observed in autistic patients [57-59] , and similar deficits in explaining the increased excitability observed in autism
[66,67]
social behavior have been reported by Lugo et al. and spectrum disorder .
[56]
Kwon et al. . It is worth noting that voluntary running Children prenatally exposed to valproic acid are more
[19]
did not counteract this memory deficit (Figure 4B). These vulnerable to developing autism spectrum disorders [68,69] .
results suggest that 10 days of voluntary running may According to Rinaldi et al. , valproic acid increases the
[70]
be insufficient to induce changes in social recognition expression of NMDA receptor subunits NR2A and NR2B
memory damage, and a longer period of running might while decreasing PTEN gene expression. In the present
be needed to reverse this behavior effect, as reported by study, we did not observe any differences among the groups
other studies [52,60] . The contradictory data among studies in the expression of the phosphorylated form of NR1 and
could be attributed to various factors, such as gender, age, the total NR2B. However, we observed an increase in total
animal lineage, running wheel, diet, and environment . NR1 expression in HT mice (Figure 6E). Some studies
[53]
In relation to the environment, although some studies with autism spectrum disorder models, as reviewed
in the literature have used protocols similar to ours (i.e., by Wang et al. , have shown that both an increase and
[71]
the use of one animal and one running wheel per cage to decrease in NMDAR1 phosphorylation can occur.
ensure that all runners indeed ran in the wheel) [61,62] , the Another protein that can be modulated by the PI3K-
varying results could be due to differences in mouse lineage AKT pathway is S6K1, which, in turn, phosphorylates S6.
(background lineage of PTEN-conditioned knockout S6 is a ribosomal 40S constituent involved in regulating
driven by enolase promoter) and the gender (female) as protein translation and, subsequently, cell growth and
our results did not show an improvement in sociability proliferation . Furthermore, S6K can also regulate
[5]
induced by voluntary running in WT animals. Therefore, protein translation . Studies have demonstrated that
[72]
further studies are necessary to determine whether a exercise can augment the phosphorylation of S6K in
longer period of voluntary physical exercise can counteract skeletal muscle, which seems to be related to an increase
PTEN-induced social recognition memory deficit. in muscle mass [73,74] . In addition to this, S6K seems to
In the inhibitory avoidance test, all the groups be involved in modulating synaptic plasticity, as shown
demonstrated memory of the avoidance stimulus by Caccamo et al. , who observed that suppression of
[75]
(Figure 5). In this study, female mice did not exhibit S6K1 expression improved synaptic plasticity and spatial
impaired aversive memory, which contrasts with the memory deficits in an Alzheimer’s disease animal model.
results observed in male mice from the same lineage in This improvement could be explained by the fact that
our previous study. In that study, a 30-day of intermittent sustained glutamatergic signaling activation, which has
fasting protocol was able to recover fear memory deficit in been shown to occur in neurodegenerative processes ,
[76]
male HT mice . These findings align with the fact that the can inhibit S6K . Our study showed that HT mice have
[39]
[77]
Volume 2 Issue 3 (2023) 9 https://doi.org/10.36922/an.0872