Effects of lithium on locomotor activity and circadian rhythm of honey bees.

Lithium has been considered a potential acaricidal agent against the honey bee (Apis mellifera) parasite Varroa. It is known that lithium suppresses elevated activity and regulates circadian rhythms and light response when administered to humans as a primary therapeutic chemical for bipolar disorder and to other bipolar syndrome model organisms, given the crucial role of timing in the bee's foraging activity and the alternating sunlight vs dark colony environment bees are exposed, we explored the influence of lithium on locomotor activity (LMA) and circadian rhythm of honey bees. We conducted acute and chronic lithium administration experiments, altering light conditions and lithium doses to assess LMA and circadian rhythm changes. We fed bees one time 10 µl sucrose solution with 0, 50, 150, and 450 mM LiCl in the acute application experiment and 0, 1, 5, and 10 mmol/kg LiCl ad libitum in bee candy in the chronic application experiment. Both acute and chronic lithium treatments significantly decreased the induced LMA under constant light. Chronic lithium treatment disrupted circadian rhythmicity in constant darkness. The circadian period was lengthened by lithium treatment under constant light. We discuss the results in the context of Varroa control and lithium's effect on bipolar disorder.

Lithium salts: assessment of their chronic and acute toxicities to honey bees and their anti-Varroa field efficacy.

BACKGROUND: Varroa control is essential for the maintenance of healthy honey bee colonies. Overuse of acaricides has led to the evolution of resistance to those substances. Studies of the short-term acaricidal effects and safety of various lithium (Li) salts recently have been reported. This study examined the long-term in vitro and in vivo bee toxicities, short-term motor toxicity to bees and long-term anti-Varroa field efficacy of several Li salts. RESULTS: In an in vitro chronic-toxicity assay, lithium citrate (18.8 mm) was the most toxic of the examined salts, followed by lithium lactate (29.5 mm), and lithium formate (32.5 mm). In terms of acute locomotor toxicity to bees, all of the Li salts were well-tolerated and none of the treatment groups differed from the negative control group. In an in vitro survival study, all of the Li treatments significantly reduced bee life spans by a factor of 1.8-7.2, as compared to the control. In terms of life expectancy, lithium citrate was the most toxic salt, with no significant differences noted between lithium formate and lithium lactate. In the bee-mortality field study, none of the examined treatments differed from the negative control. Amitraz and lithium formate exhibited similar acaricide effects, which were significantly different from those observed for lithium lactate and the negative control. CONCLUSION: In light of lithium formate's honey bee safety and efficacy as an acaricide, additional sublethal toxicity studies in brood, drones and queens, as well as tests aimed at the optimization of administration frequency are warranted. © 2022 Society of Chemical Industry.

The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p < 0.05). Dexanabinol treatment reduced NO concentration and cathepsin activity to the control level (p > 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p < 0.05). However, dexanabinol treatment lowered both of these (p < 0.05). We conclude that dexanabinol might be a useful agent for the treatment of stroke patients.

Nitric oxide level and adenosine deaminase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage.

OBJECTIVE: Adenosine and nitric oxide (NO) are known as vasodilatators. We investigated adenosine deaminase (ADA) activity and NO concentration in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH). METHODS: Forty patients with SAH and 10 controls were included in the study. Nitrate level and ADA activity were measured in CSF. SAH patients were grouped according to the presence of angiographic vasospasm, Hunt and Hess grading, Glasgow Coma Scale (GCS) and Fisher Grade (FG). RESULTS: The level of NO markers in SAH patients decreased when compared to that in the control group (p < 0.05). However, NO markers in patients with vasospasm was higher than in that of patients without vasospasm (p < 0.05). ADA activity increased in patients with SAH (p < 0.01) and also patients with angiographic vasospasm (p < 0.05). ADA activity in the poor-grade SAH group was higher than that in the good-grade SAH group. The group with the lower GCS showed increased ADA activity compared to those with a higher GCS score (p < 0.01). Furthermore, patients with FG 4 had a higher level of ADA activity compared to FG 1 and 2 and FG 3 (p < 0.001 and p < 0.01, respectively). CONCLUSION: Decreased NO level may participate in the early development of vasospasm. However, the increased level of ADA activity in the SAH patients with the poor clinical and consciousness level may have resulted from the ischemic cerebral insult.

Appetitive reversal learning differences of two honey bee subspecies with different foraging behaviors.

We aimed to examine mechanistically the observed foraging differences across two honey bee, Apis mellifera, subspecies using the proboscis extension response assay. Specifically, we compared differences in appetitive reversal learning ability between honey bee subspecies: Apis mellifera caucasica (Pollman), and Apis mellifera syriaca (Skorikov) in a "common garden" apiary. It was hypothesized that specific learning differences could explain previously observed foraging behavior differences of these subspecies: A.m. caucasica switches between different flower color morphs in response to reward variability, and A.m. syriaca does not switch. We suggest that flower constancy allows reduced exposure by minimizing search and handling time, whereas plasticity is important when maximizing harvest in preparation for long winter is at a premium. In the initial or Acquisition phase of the test we examined specifically discrimination learning, where bees were trained to respond to a paired conditioned stimulus with an unconditioned stimulus and not to respond to a second conditioned stimulus that is not followed by an unconditioned stimulus. We found no significant differences among the subspecies in the Acquisition phase in appetitive learning. During the second, Reversal phase of the experiment, where flexibility in association was tested, the paired and unpaired conditioned stimuli were reversed. During the Reversal phase A.m. syriaca showed a reduced ability to learn the reverse association in the appetitive learning task. This observation is consistent with the hypothesis that A.m. syriaca foragers cannot change the foraging choice because of lack of flexibility in appetitive associations under changing contingencies. Interestingly, both subspecies continued responding to the previously rewarded conditioned stimulus in the reversal phase. We discuss potential ecological correlates and molecular underpinnings of these differences in learning across the two subspecies. In addition, in a supplemental experiment we demonstrated that these differences in appetitive reversal learning do not occur in other learning contexts.

Effects of chronic ethanol consumption on brain synaptosomes and protective role of betaine.

To evaluate the cytotoxic effects of chronic ethanol consumption on brain cerebral synaptosomes and preventive role of betaine as a methyl donor and S-adenosylmethionine precursor, 24 male Wistar rats were divided into three groups: control, ethanol (8 g/kg/day) and ethanol plus betaine(0.5% w/v) group. Animals were fed 60 ml/diet per day for two months, then sacrificed. Malondialdehyde (MDA), protein carbonyl contents and adenosine deaminase (ADA) activities were determined in synaptosomal/mitochondrial enriched fraction isolated from rat cerebral cortexes. When compared to controls, ethanol containing diet significantly increased MDA levels (P < 0.05), also increased protein carbonyl levels and adenosine deaminase activities. But these were not statistically significant (P > 0.05). However, adding betaine to ethanol containing diet caused a significant decrease in MDA, protein carbonyl levels and adenosine deaminase activities (P < 0.05). These results indicate that betaine may appear as a protective nutritional agent against cytotoxic brain damage induced by chronic ethanol consumption.