Per- and polyfluoroalkyl substances (PFAS) are a group
of persistent
environmental pollutants that are ubiquitously found in the environment
and virtually in all living organisms, including humans. PFAS cross
the blood–brain barrier and accumulate in the brain. Thus,
PFAS are a likely risk for neurotoxicity. Studies that measured PFAS
levels in the brains of humans, polar bears, and rats have demonstrated
that some areas of the brain accumulate greater amounts of PFAS. Moreover,
in humans, there is evidence that PFAS exposure is associated with
attention-deficit/hyperactivity disorder (ADHD) in children and an
increased cause of death from Parkinson’s disease and Alzheimer’s
disease in elderly populations. Given possible links to neurological
disease, critical analyses of possible mechanisms of neurotoxic action
are necessary to advance the field. This paper critically reviews
studies that investigated potential mechanistic causes for neurotoxicity
including (1) a change in neurotransmitter levels, (2) dysfunction
of synaptic calcium homeostasis, and (3) alteration of synaptic and
neuronal protein expression and function. We found growing evidence
that PFAS exposure causes neurotoxicity through the disruption of
neurotransmission, particularly the dopamine and glutamate systems,
which are implicated in age-related psychiatric illnesses and neurodegenerative
diseases. Evaluated research has shown there are highly reproduced
increased glutamate levels in the hippocampus and catecholamine levels
in the hypothalamus and decreased dopamine in the whole brain after
PFAS exposure. There are significant gaps in the literature relative
to the assessment of the nigrostriatal system (striatum and ventral
midbrain) among other regions associated with PFAS-associated neurologic
dysfunction observed in humans. In conclusion, evidence suggests that
PFAS may be neurotoxic and associated with chronic and age-related
psychiatric illnesses and neurodegenerative diseases. Thus, it is
imperative that future mechanistic studies assess the impact of PFAS
and PFAS mixtures on the mechanism of neurotransmission and the consequential
functional effects.
Parkinson’s
disease (PD) is a debilitating neurodegenerative
disorder. Early symptoms include motor dysfunction and impaired olfaction.
Toxic aggregation of α-synuclein (aSyn) in the olfactory bulb
(OB) and substantia nigra pars compacta (SNpc) is a hallmark of PD
neuropathology. Intranasal (IN) carnosine (2 mg/d for 8 weeks) was
previously demonstrated to improve motor behavior and mitochondrial
function in Thy1-aSyn mice, a model of PD. The present studies evaluated
the efficacy of IN carnosine at a higher dose in slowing progression
of motor deficits and aSyn accumulation in Thy1-aSyn mice. After baseline
neurobehavioral assessments, IN carnosine was administered (0.0, 2.0,
or 4.0 mg/day) to wild-type and Thy1-aSyn mice for 8 weeks. Olfactory
and motor behavioral measurements were repeated prior to end point
tissue collection. Brain sections were immunostained for aSyn and
tyrosine hydroxylase (TH). Immunopositive cells were counted using
design-based stereology in the SNpc and OB mitral cell layer (MCL).
Behavioral assessments revealed a dose-dependent improvement in motor
function with increasing carnosine dose. Thy1-aSyn mice treated with
2.0 or 4.0 mg/d IN carnosine exhibited fewer aSyn-positive (aSyn(+))
cell bodies in the SNpc compared to vehicle-treated mice. Moreover,
the number of aSyn(+) cell bodies in carnosine-treated Thy1-aSyn mice
was reduced to vehicle-treated wild-type levels in the SNpc. Carnosine
treatment did not affect the number of aSyn(+) cell bodies in the
OB-MCL or the number of TH(+) cells in the SNpc. In summary, intranasal
carnosine treatment decreased aSyn accumulation in the SNpc, which
may underlie its mitigation of motor deficits in the Thy1-aSyn mice.
Physical therapy of the upper extremities has been demonstrated to be a useful treatment for pediatric cerebral palsy. This paper describes a test of a custom-made Kinect-based health game called Burnie that gamifies upper arm physical therapy for pediatric cerebral palsy patients by placing the player in the role of a bird navigating a nature-themed obstacle course. Precise repetition of the games can be a difficult learning task as the player's feedback of correct learning is kinesthetic rather than visual. This study seeks to illuminate the affective element of learning specific physical poses within a video game learning paradigm. This pilot study evaluates the game for player satisfaction along the dimensions of graphics, controls, and overall enjoyment. In preparation for later testing with the target population of pediatric patients, an initial pilot study was conducted with undergraduate students as test subjects using a post-test only control group design. After subjects played the game for fifteen minutes, they evaluated the game along the aforementioned dimensions using a pen and paper survey. Average observed ratings (on a 10 point scale, higher being better) were: 7.65, 5.4, and 6.75, respectively. These results indicate that Burnie is an enjoyable game experience, but in order to maximize effectiveness more research needs to be done on the control scheme to determine why it was rated lower than the rest of the game. Identification of the specific factors that contribute to control enjoyment is recommended. This work contributes to HCI by presenting a new method for leveraging computers to improve the quality of life of pediatric sufferers of cerebral palsy, and contributes to education by providing a new means for teaching individuals how to perform specific therapeutic gestures within a game-based learning session.
Given the limited sample size in this study, it cannot be stated with certainty that greater pose accuracy will occur if a pregame tutorial level is administered. However, a trend was observed along most measures that the tutorial group achieved greater accuracy scores than the verbal instruction group. Further study with greater statistical power is strongly recommended.
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