While epilepsy can affect anyone at any age, it is roughly three times more prevalent in people over age 65. Prevalence and incidence of epilepsy will rise as the global population becomes increasingly older. Epilepsy in older people is associated with comorbidities such as neurodegeneration. We have previously demonstrated that administration of the antiseizure medicine (ASM), lacosamide (LCM), to young, corneally kindled mice was associated with increased levels of Ki-67 positive/NeuN-positive neurons relative to vehicle (VEH)-treated kindled or untreated sham-kindled animals in the dentate gyrus of dorsal hippocampus of the brain, suggesting beneficial effects of LCM on neurogenesis in young mice with chronic seizures (Zierath et al, IJMS 2023). We thus hypothesized that LCM administration to aged wild-type mice with chronic seizures could increase the number of Ki-67 positive/NeuN-positive hippocampal neurons, indicating neurogenesis. To test this hypothesis, I randomized mice aged >30 months-old to receive either LCM (4.5 mg/kg) or VEH treatment administered prior to each seizure stimulation. Mice were then kindled with a twice-daily 3 second, 60 Hz transcorneal stimulation over 15 days. After 27 stimulations to evoke consistent behavioral seizures, mice were euthanized, and brains collected for immunohistochemistry. Tissues were labeled for Ki-67, marking for neurogenesis, GFAP for astroglial cells, and NeuN, for mature neurons. Unlike in similarly treated young, kindled male mice, LCM administration significantly slowed male mouse kindling acquisition rate (p=0.0022) compared with VEH-treated littermates. There was no significant effect of LCM administration on kindling rate in aged female mice. Further, LCM was poorly tolerated in aged male but not female mice, revealing significant sexual dimorphism in ASM tolerability with chronic administration to aged mice. Ongoing immunohistochemistry is quantifying Ki-67 expression to further demonstrate whether LCM administration induces hippocampal neurogenesis in aged mice with chronic seizures.

Sudden unexpected death in epilepsy (SUDEP) is the most severe consequence of uncontrolled epilepsy. SUDEP is a multifactorial disease associated with serotonin (5-HT) imbalance and exacerbated neuroinflammation. Unfortunately, current preclinical animal models do not adequately explain all underlying causes of these events or their subsequent effects. Seizures are a common comorbidity in Alzheimer’s disease (AD), especially in patients with genetic variants in amyloid precursor protein (APP) and presenilin 1 (PSEN1) and 2 (PSEN 2). Clinical evidence suggests that seizures in AD patients worsen their cognitive decline and increase mortality rate compared to AD patients without seizures. Our lab demonstrated that 2-month-old mice with an APP/PS1 variant subjected to chronic evoked seizures resulted in premature mortality, heightened neuroinflammation, and altered 5-HT system enzyme expression prior to AD onset. These findings reveal a novel preclinical platform to test potential preventative agents for SUDEP. Given the relationship between seizures and AD, I aim to prevent seizure-induced premature mortality, and define 5-HT and neuroinflammatory changes in APP/PS1 mice treated with 2 investigational agents: lorcaserin, a selective 5-HT receptor agonist, and cannabidiol (CBD), a broad-spectrum anti-inflammatory and 5-HT modulator. I hypothesize that targeting seizure-induced neuroinflammation and the dysregulated 5-HT system with these compounds will decrease premature seizure-induced mortality. To assess this, 2-month-old APP/PS1 mice underwent corneal kindling procedure to evoke investigator-controlled chronic seizures and received lorcaserin (10 mg/kg) or CBD (100 mg/kg) via the intraperitoneal route. Then, I tracked survival during the chronic seizure period and performed molecular analysis to quantify neuroinflammatory proteins and 5-HT system enzyme expression. Our preliminary results show that mice treated with lorcaserin or CBD had a mortality rate of 10% compared to 75% in the untreated APP/PS1 mice. Future directions include using these compounds in other preclinical SUDEP models to confirm the translational potential of these medications to clinical use.

The war in Ukraine has resulted in a high number of refugees fleeing to nearby countries. The literature on the economic effects followed by such migration is very limited. In particular, the effects of the influx of refugees on the labor markets of host countries are broadly researched. The purpose of this study is to analyze such effects in the context of Poland and Ukrainian refugees. This study investigates the effects of labor supply shocks caused by refugees on Poland’s labor market outcomes. Analysis was conducted using data on Ukrainian refugee migration within Poland, and the labor market factors such as wages and employment. The findings of this research help to have a clearer understanding of the expected effects on labor markets in similar refugee situations as Poland. Recognizing these effects can help countries be more prepared when facing labor market supply shocks which is beneficial for both the host country and the refugees.