Transgenic mice with increased astrocyte expression of CCL2 show altered behavioral effects of alcohol

Abstract

Emerging research provides strong evidence that activation of CNS glial cells occurs in neurological diseases and brain injury and results in elevated production of neuroimmune factors. These factors can contribute to pathophysiological processes that lead to altered CNS function. Recently, studies have also shown that both acute and chronic alcohol consumption can produce activation of CNS glial cells and the production of neuroimmune factors, particularly the chemokine CCL2. The consequences of alcohol-induced increases in CCL2 levels in the CNS have yet to be fully elucidated. Our studies focus on the hypothesis that increased levels of CCL2 in the CNS produce neuroadaptive changes that modify the actions of alcohol on the CNS. We utilized behavioral testing in transgenic mice that express elevated levels of CCL2 to test this hypothesis. The increased level of CCL2 in the transgenic mice involves increased astrocyte expression. Transgenic mice and their non-transgenic littermate controls were subjected to one of two alcohol exposure paradigms, a two-bottle choice alcohol drinking procedure that does not produce alcohol dependence or a chronic intermittent alcohol procedure that produces alcohol dependence. Several behavioral tests were carried out including the Barnes Maze, Y-Maze, cued and contextual conditioned fear test, light-dark transfer, and forced swim test. Comparisons between alcohol naïve, non-dependent, and alcohol dependent CCL2 transgenic and non-tg mice show that elevated levels of CCL2 in the CNS interact with alcohol in tests for alcohol drinking, spatial learning and associative learning.

Effects of Withdrawal from Chronic Intermittent Ethanol Exposure on Sleep Characteristics of Female and Male Mice

“…First of all, these results indicated that, although they drink more ethanol overall, female C57BL/6J mice develop escalated EtOH drinking with CIE exposure to an equal degree as males. This is consistent with our previous findings (Bray et al, 2017) as well as others (Bergeson et al, 2016; Crabbe et al, 2012). Another recent study showed escalated EtOH drinking in male C57BL/6J mice, but not in females (Jury et al, 2016); however these results were based on 24hr EtOH drinking as opposed to the limited access model most commonly associated with CIE models.…”

Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

“…Based on these studies, silibinin potentially acts on multiple targets to inhibit AD pathologies. However, the effects of In the present study, learning and memory deficits were assessed using the Y-maze test, novel object recognition test and Morris water maze test, which are widely used methods to investigate the behaviors of mice [17][18][19][20]. The contents of soluble and insoluble Aβ and Aβ plaques are increased in 6-month-old APP/PS1 mice, comparable to patients with AD [21,22].…”

The Kappa Opioid Receptor is required for some intermittent alcohol drinking induced changes in stress and threat responding in male C57BL/6J mice

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