Environmental Enrichment Mitigates Detrimental Cognitive Effects of Ketogenic Diet in Weanling Rats.

For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25-40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the child.

Effects of PI3K inhibition and low docosahexaenoic acid on cognition and behavior.

Alterations in two components of the brain's insulin signaling pathway, docosahexaenoic acid (DHA) content and phosphoinositide 3-kinase (PI3K) activity, have been implicated in the insulin resistance that is central to type II diabetes mellitus (DM). A 2- to 3-fold increased risk of developing Alzheimer's disease (AD) in patients with type II DM suggests a potential link between cognition and insulin action. The current study was designed to examine the impact of DHA dietary content and PI3K activity on learning, memory, depression, and anxiety in rodents.

Estradiol-induced conditioned place preference may require actions at estrogen receptors in the nucleus accumbens.

Intrinsic rewarding effects of estradiol (E(2)) may underlie some of the sex differences that emerge postpuberty for the prevalence of drug use and behavioral responses to drugs, but the effects and mechanisms of E(2) for reward have not been well characterized. Conditioned place preference (CPP), as measured by the time spent on the nonpreferred/drug-associated side of the chamber, was utilized as a functional assay to investigate the effects and mechanisms of E(2) in the nucleus accumbens for reward. To determine whether intracellular estrogen receptors (ERs) are important for E(2)-induced CPP, rats were administered E(2) (10 microg; subcutaneously (s.

Ketogenic diet decreases circulating concentrations of neuroactive steroids of female rats.

Ketogenic diet (KD) is used to manage intractable epilepsy; however, the mechanisms underlying its therapeutic effects are not known. Steroid hormones, such as progesterone and testosterone, are derived from cholesterol, and are readily 5alpha-reduced to dihydroprogesterone and dihydrotestosterone, which are subsequently converted to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) and 3alpha-androstanediol, neuroactive steroids that can influence seizures. The present study examined the effects of the KD on circulating concentrations of these neuroactive steroids, and their precursors, in intact female rats.

Gonadal, adrenal, and neuroactive steroids' role in ictal activity.

Of the many people that have epilepsy, only about 70% achieve seizure control with traditional pharmacotherapies. Steroids have long been known to influence ictal activity and may have a therapeutic role. This review summarizes recent investigations that have enhanced knowledge of the effects and mechanisms of gonadal, adrenal, and neuroactive steroids on seizure processes.

Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase.

The importance of progesterone's (P(4)) metabolism by the 5 alpha-reductase type I enzyme was examined in homozygous and heterozygous 5 alpha-reductase type I knockout mice and their wild-type siblings. P(4) (1.0 mg) or vehicle was administered and effects on motor, anxiety, nociceptive, and depression behavior were observed.

Testosterone enhances aggression of wild-type mice but not those deficient in type I 5alpha-reductase.

Testosterone's (T) aggression-enhancing effects may be mediated in part by its 5alpha-reduced, 3-hydroxysteroid dehydrogenized metabolite 5alpha-androstane-3alpha,17beta-diol (3alpha-diol). To test this hypothesis, in Expt. 1 gonadectomized (gdx) C21 mice were administered T, 3alpha-diol, or vehicle and were observed in the resident intruder test of aggression 1 h later.

Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of beta hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet.

The present study was designed to evaluate the effects of acute inhibition of fatty acid oxidation on plasma levels of beta hydroxybutyrate and latency to PTZ-induced seizures in ad libitum- (AL), calorie-restricted normal rodent chow- (CR), and calorie-restricted ketogenic diet (KD)-fed young rats. Young (day 23) Sprague-Dawley rats were fasted for 8 h and then fed their respective diets for 21 days. On day 21 of the diet rats in each group received either saline or the fatty acid oxidation inhibitor mercaptoacetate (MA; 46 mg/kg intraperitoneally (i.