Parkinson's disease involves loss of dopamine (DA)-producing neurons in the substantia nigra, associated with fewer pre-synaptic DA transporters (DATs) but more post-synaptic dopaminergic D 2 receptors in terminal areas of these neurons.Hypothesis-Arachidonic acid (AA) signaling via post-synaptic D 2 receptors coupled to cytosolic phospholipase A 2 (cPLA 2 ) will be reduced in terminal areas ipsilateral to a chronic unilateral substantia nigra lesion in rats given D-amphetamine, which reverses the direction of the DAT, but will be increased in rats given quinpirole, a D 2 -receptor agonist.Methods-D-amphetamine (5.0 mg/kg i.p.), quinpirole (1.0 mg/kg i.v.), or saline was administered to unanesthetized rats having a chronic unilateral lesion of the substantia nigra. AA incorporation coefficients, k* (radioactivity/integrated plasma radioactivity), markers of AA signaling, were measured using quantitative autoradiography in 62 bilateral brain regions following intravenous [1-14 C]AA.Results-In rats given saline (baseline), k* was elevated in 13 regions in the lesioned compared with intact hemisphere. Quinpirole increased k* in frontal cortical and basal ganglia regions bilaterally, more so in the lesioned than intact hemisphere. D-amphetamine increased k* bilaterally but less so in the lesioned hemisphere.Conclusions-Increased baseline elevations of k* and increased responsiveness to quinpirole in the lesioned hemisphere are consistent with their higher D 2 -receptor and cPLA 2 activity levels, whereas reduced responsiveness to D-amphetamine is consistent with dropout of pre-synaptic elements containing the DAT. In vivo imaging of AA signaling using dopaminergic drugs can identify pre-and post-synaptic DA changes in animal models of Parkinson's disease.
Previous research shows that social network components are associated with cognitive function later in life. However, fewer studies consider different cognitive domains or disaggregate the social network by relationship type. Using data from 2,553 participants aged 65 or older in the Health and Retirement Study's Harmonized Cognitive Assessment Protocol, this study examined relationships between social network structure (i.e., size, contact frequency) and quality (i.e., support, strain) and performance in five cognitive domains (i.e., episodic memory, executive function, visuoconstruction, language, and processing speed) 2-4 years later, controlling for sociodemographics and previous global cognition. Separate linear regressions were conducted for each cognitive outcome. When averaged across relationship types, network size was not associated with any domain. Contact frequency was positively associated with all domains except episodic memory. Support and strain were negatively associated with all cognitive domains. When considering individual relationship types, larger friend networks were positively associated with visuoconstruction, and greater contact frequency with friends was positively associated with all cognitive domains. Larger family networks were associated with worse executive function, visuoconstruction, and speed. Strain from friends had a negative relationship with every domain except episodic memory. Support from family was negatively associated with episodic memory, executive function, and language. These associations were equivalent to one to 3.5 years of cognitive aging. These results showed that both social network structure and quality may be consequential for cognitive functioning and that links between social relations and cognition differ across domains and as a function of relationship type.
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