Accumulation of beta-amyloid (Aβ) in the brain has been implicated as a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer's disease. Beta-amyloid may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain. This study set out to investigate whether a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase (CAT-SKL), is able to reduce the toxicity induced by intracerebroventricular injection of Aβ in the mature rat brain. Histopathological and immunohistochemical analyses were used to evaluate neuroinflammation, and neuronal loss. Spatial learning and reference memory was assessed using the Morris water maze. CAT-SKL treatment was able to reduce the pathology induced by Aβ toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aβ animals showed deficits in long-term reference memory in the Morris water maze, while Aβ animals treated with CAT-SKL did not demonstrate long-term memory impairments. This preclinical data provides support for the use of CAT-SKL in reducing neuroinflammation and long-term reference memory deficits induced by Aβ

Beta-amyloid (Aβ) accumulation, neuroinflammation, basal forebrain cholinergic loss and hippocampal degeneration are well-described pathologies associated with Alzheimer's disease (AD). However, the role that age plays in the susceptibility of the brain to these AD pathologies and the relationships between them is still not well understood. This study investigated the age-related response to intracerebroventricular injection of Aβ(25-35) in 3-, 6- and 9-month-old rats. Aβ toxicity resulted in an age-related increase in cholinergic loss and microglial activation in the basal forebrain along with neuronal loss in the hippocampal CA3 subfield. Performance in the Morris water maze revealed impairments in long-term reference memory in 6-month-old Aβ administered animals, which was not seen in 3-month-old animals. These results support a role of Aβ administration in inducing age-dependent cholinergic loss and neuroinflammation, and additionally provide evidence for a more age-appropriate model of adult-onset Aβ toxicity demonstrating pathological changes that reflect the early stages of AD pathogenesis including neuroinflammation, cholinergic loss and beginning stages of memory impairment.

Background: Decreased oxygenation of muscle may be accentuated during exercise at high altitude. Monitoring the oxygen saturation of muscle (SmO 2) during hand grip exercise using near infrared spectroscopy during acute exposure to hypoxia could provide a model for a test of muscle performance without the competing cardiovascular stresses that occur during a cycle ergometer or treadmill test. The purpose of this study was to examine and compare acute exposure to normobaric hypoxia versus normoxia on deoxygenation and recruitment of the flexor digitorum superficialis (FDS) during submaximal intermittent handgrip exercise (HGE) in healthy adults. Methods: Twenty subjects (11 M/9 F) performed HGE at 50% of maximum voluntary contraction, with a duty cycle of 2 s:1 s until task failure on two occasions one week apart, randomly assigned to normobaric hypoxia (FiO 2 = 12%) or normoxia (FiO 2 = 21%). Near-infrared spectroscopy monitored SmO 2 , oxygenated (O 2 Hb), deoxygenated (HHb), and total hemoglobin (tHb) over the FDS. Surface electromyography derived root mean square and mean power frequency of the FDS. Results: Hypoxic compared to normoxic HGE induced a lower FDS SmO 2 (63.8 ± 2.2 vs. 69.0 ± 1.5, p = 0.001) and both protocols decreased FDS SmO 2 from baseline to task failure. FDS mean power frequency was lower during hypoxic compared to normoxic HGE (64.0 ± 1.4 vs. 68.2 ± 2.0 Hz, p = 0.04) and both decreased mean power frequency from the first contractions to task failure (p = 0.000). Under both hypoxia and normoxia, HHb, tHb and root mean square increased from baseline to task failure whereas O 2 Hb decreased and then increased during HGE. Arterial oxygen saturation via pulse oximetry (SpO 2) was lower during hypoxia compared to normoxia conditions (p = 0.000) and heart rate and diastolic blood pressure only demonstrated small increases. Task durations and the tension-time index of HGE did not differ between normoxic and hypoxic trials.

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Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke. For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.