Epigenetic Conditioning Induces Intergenerational Resilience to Dementia in a Mouse Model of Vascular Cognitive Impairment

Background: Vascular cognitive impairment and dementia (VCID), which occurs immediately or in delayed fashion in 25-30% of stroke survivors, or secondary to chronic cerebral hypoperfusion, is the second leading cause of dementia following Alzheimers disease. To date, efficacious therapies are unavailable. We have shown previously in mice that repetitive hypoxic preconditioning (RHC) induces a long-lasting resilience to acute stroke (Stowe et al., 2011). More recently, we documented that untreated, first-generation adult progeny of mice exposed to RHC prior to mating are protected from retinal ischemic injury (Harman et al., 2020), consistent with accumulating evidence supporting the concept that long-lasting phenotypes induced epigenetically by intermittent stressors may be heritable. We undertook the present study to test the hypothesis that RHC will induce resilience to VCID, and that such RHC-induced resilience can also be inherited. Methods: Chronic cerebral hypoperfusion (CCH) was induced in C57BL/6J mice secondary to bilateral carotid artery stenosis with microcoils in both the parental (F0) generation, and in their untreated first-generation (F1) offspring. Cohorts of F0 mice were directly exposed to either 8 wks of RHC (1 h of systemic hypoxia 11% oxygen, 3x/week) or normoxia prior to CCH. Cohorts of F1 mice were derived from F0 mice treated with RHC prior to mating, and untreated, normoxic controls that were age-matched at the time of stenosis induction. Demyelination in the corpus callosum of F0 mice was assessed following 3 months of CCH by immunohistochemistry. Mice from both generations were assessed for short-term recognition memory in vivo by novel object preference (NOP) testing following 3 months of CCH, and a month thereafter, ex vivo measurements of CA1 hippocampal long-term potentiation (LTP) were recorded from the same animals as a metric of long-lasting changes in synaptic plasticity. Results: Three months of CCH caused demyelination and concomitant impairments in recognition memory in control mice from both generations. However, these CCH-induced memory impairments were prevented in F0 animals directly treated with RHC, as well as in their untreated adult F1 progeny. Similarly, hippocampal LTP was preserved in the 4-month CCH cohorts of mice directly treated with RHC, and in their untreated offspring with CCH. Conclusions: Our findings demonstrate that RHC or other repetitively-presented, epigenetic-based therapeutics may hold promise for inducing a long-lasting resilience to VCID in treated individuals, and in their first-generation adult progeny.

Water Loss and Desiccation Tolerance of the Two Yearly Generations of Adult and Nymphal Kudzu Bugs, Megacopta cribraria (Hemiptera: Plataspidae)

Water loss rate, percentage total body water content (%TBW), cuticular permeability (CP), and desiccation tolerance were investigated in adult and immature stages of the invasive kudzu bug, Megacopta cribraria (Fab.) (Hemiptera: Plataspidae), a serious soybean pest and an urban nuisance. Adults and all five nymphal instars were weighed prior to and 2, 4, 6, 8, 10, and 24 h after desiccated at 30 ± 1°C and 0–2% RH. Both % initial mass and %TBW loss increased linearly with time of desiccation. Rates of loss ranged from approximately 1–7%/h. Mortality occurred at 10 h after desiccation. Desiccation tolerance (%TBW lost at death) ranged between 25.6% for first-generation adult females and 75% for first-generation fifth-instar nymphs. First-generation first-instar nymphs had significantly greater %TBW (88.9%) than the other generations and instars, whereas second-generation fifth instars had the lowest %TBW (62.4%). The CP value of first-generation adult females (12.3 ± 1.6 µg cm−1 h−1 mmHg−1) was the greatest across generations. First-generation first instars had the greatest mass loss (111.11 mg/g) among all instars and generations, whereas overwintered second-generation adult females had the lowest mass loss (18.39) across generations. This study demonstrated that desiccation stress differentially affected the survival of adult and nymphal kudzu bugs and may imply that environmental stress can affect the relative abundance of this species in the fields and around homes.

Heterogony in Cycloneuroterus (Hymenoptera: Cynipidae: Cynipini) From Rearing Experiments and DNA Barcoding

Heterogony was confirmed in the cynipid genus Cycloneuroterus Melika and Tang in rearing experiments with DNA barcoding. These experiments involved Cycloneuroterus gilvus Tang and Melika, which was previously only described from the sexual generation adult. The first rearing experiment was conducted using unidentified asexual generation females collected from Quercus gilva Blume, and gall formation by the sexual generation offspring was confirmed on folded or unfolded young leaves of Q. gilva. The second experiment was conducted using sexual generation males and females reared from the leaf galls collected from Q. gilva, and gall formation by the asexual generation offspring was observed on leaves of Q. gilva. Based on the morphological features of the sexual generation adults and galls, this species was identified as C. gilvus. The species identity of wasp specimens of sexual and asexual generations used in the rearing experiments was cross-checked using DNA barcoding with the partial sequences of the cytochrome c oxidase subunit I (COI) region (658 bp). The asexual generation adult and gall of C. gilvus are described based on these results. The importance of ‘closing the life cycle,’ in this case a demonstration of heterogony, in oak gall wasps (Cynipini) is discussed.