Lithium protects against glucocorticoid induced neural progenitor cell apoptosis in the developing cerebellum

Abstract

Respiratory dysfunction is one of the most common causes of death associated with premature birth (Barton et al., 1999). In the United States, 7–10% of pregnant women receive antenatal glucocorticoid (GC) therapy (Matthews et al., 2004), while approximately 19% of very low birth weight infants receive postnatal GC therapy (Jobe, 2009). Clinical research suggests that GC treatment causes permanent neuromotor and cognitive deficits (Yeh et al., 2004) and stunts cerebellar growth (Parikh et al., 2007; Tam et al., 2011). We previously reported that GC-mediated neural progenitor cell (NPC) apoptosis may be responsible for cerebellar neuropathology (Maloney et al., 2011; Noguchi et al., 2008; Noguchi et al., 2011). The goal of the current study was to determine whether lithium protects NPCs from GC neuroapoptosis in vivo and in vitro. Given that it protects against a range of brain insults, we hypothesized that lithium would significantly attenuate GC induced NPC toxicity. We report that acute lithium pretreatment provides potent, cell-intrinsic neuroprotection against GC induced NPC toxicity in vivo and in vitro.

Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity

“…Brains were harvested and postfixed in 4% PFA for 24 h at 4 °C, embedded in 3% agar, and serially sectioned in the sagittal plane at 75 μm on a vibratome. Every 8th section was immunolabeled for activated caspase 3 (AC3) as previously described [17]. Commitment to cell death occurs prior to cell surface expression of AC3, making AC3 a reliable marker of apoptosis.…”

Lithium Reversibly Inhibits Schwann Cell Proliferation and Differentiation Without Inducing Myelin Loss

“…Additional benefits of lithium therapy include neuroprotective [14,15], anti-inflammatory [16] and anti-apoptotic effects [17], which have been exploited to treat central nervous system trauma [18,19] and chronic neurodegenerative diseases, such as Huntington’s disease, amyotrophic lateral sclerosis and Parkinson’s disease [20,21]. In the peripheral nervous system, it has been shown that lithium administration can foster functional recovery and re-myelination after injury [22,23].…”

Dexmedetomidine protects against glucocorticoid induced progenitor cell apoptosis in neonatal mouse cerebellum

“…Thus, brains were immunolabeled for AC3 per laboratory protocol [9, 13]. Briefly, six hours after initial injection, pups were deeply anesthetized and transcardially perfused via the left ventricle with 4% paraformaldehyde in 0.1M Tris buffer.…”

“…Semiquantitative analysis of GINA was performed as described previously [8, 9, 13]. Briefly, a rater blind to treatment scored each cerebellum by examining several midsagittal sections per animal and evaluating the amount of AC3 positive NPCs in the EGL based on the following scale:…”

“…We recently reported that lithium provides dose-dependent neuroprotection against GINA caused by DEX [13]. However, safety concerns about lithium toxicity in neonates makes its clinical adoption challenging.…”