Chronic electroconvulsive treatment applied immediately after a training session or with a 15 min delay impairs spatial learning and memory in the Morris water maze paradigm, and this impairment is not counteracted, but rather aggravated by co-administration of a calcium channel blocker, nifedipine.
Abstract Organophosphorus ( OP ) insecticides are pest‐control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well‐defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase ( AC hE), the enzyme that hydrolyzes the neurotransmitter acetylcholine ( AC h). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short‐ and long‐term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top‐selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms . image
The few experimental studies suggest that repetitive rapid-rate transcranial magnetic stimulation (TMS) evokes in the brain functional and structural changes similar to those evoked by electroconvulsive therapy (ECT). The aim of the present work was to compare the influence of the repetitive TMS (B = 1.6 T; f = 20 and 30 Hz; t = 5 and 5.5 minutes; N = 9 and 18 days) and that of ECT (I = 150 mA; f = 50 Hz; t = 0.5 s; N = 9 days) on rats' behaviour in the tests of free field, tail flick, motor hyperactivity after administration of apomorphine and in forced swimming. None of the rats subjected to TMS suffered from convulsive attack, which followed every electroconvulsive shock. In the free field test it was detected that neither TMS nor ECT applied individually or repetitively disturbed general motor activity of rats. Repetitive electroconvulsive shocks caused analgesia, prolonging the latency of tail flick by 46% (p < 0.001). Moreover, the tail flick test revealed hyperalgesia in the rats subjected to TMS (24 and 21% of control values respectively; p = 0.05). Motor hyperactivity of rats stimulated with administration of apomorphine was intensified both by TMS (by 58% at maximum in the 30th minute of the experiment; p = 0.001) and, all the more, by ECT (by 92% at maximum at the end of the test; p = 0.01). In the forced swimming test, the greatest decrease of inertia period was observed ECT--up to 50% of control values (p = 0.001). TMS had weaker effects--the decrease amounted to 29% of control values (p = 0.01). The shortening effect depended on the parameters of TSM. The obtained results seem to confirm that TMS, like ECT, evokes in rats certain reactions suggesting its antidepressive action, but causes less undesirable effects.
A bstract : By applying calorie restriction (CR) at 30‐50% below ad libitum levels, studies in numerous species have reported increased life span, reduced incidence and delayed onset of age‐related diseases, improved stress resistance, and decelerated functional decline. Whether this nutritional intervention is relevant to human aging remains to be determined; however, evidence emerging from CR studies in nonhuman primates suggests that response to CR in primates parallels that observed in rodents. To evaluate CR effects in humans, clinical trials have been initiated. Even if evidence could substantiate CR as an effective antiaging strategy for humans, application of this intervention would be problematic due to the degree and length of restriction required. To meet this challenge for potential application of CR, new research to create “caloric restriction mimetics” has emerged. This strategy focuses on identifying compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. Microarray studies show that gene expression profiles of key enzymes in glucose (energy) handling pathways are modified by CR. Drugs that inhibit glycolysis (2‐deoxyglucose) or enhance insulin action (metformin) are being assessed as CR mimetics. Promising results have emerged from initial studies regarding physiological responses indicative of CR (reduced body temperature and plasma insulin) as well as protection against neurotoxicity, enhanced dopamine action, and upregulated brain‐derived neurotrophic factor. Further life span analyses in addition to expanded toxicity studies must be completed to assess the potential of any CR mimetic, but this strategy now appears to offer a very promising and expanding research field.
Abstract Background: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU). Methods: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats. Results: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP. Conclusion: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP.
