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The administration of 2,5-anhydro-D-mannitol has qualitatively similar effects to food deprivation as both increase levels of free fatty acids, glycerol, and ketones. Levels of plasma glucose, insulin, and norepinephrine are also comparable. However, the quantitative aspects of the two treatments are unclear. There is a greater food intake during fasting and an enhancement of plasma corticosterone and epinephrine levels during 2,5-anhydro-D-mannitol administration.

A study of the whole body energy expenditure and fuel oxidation following 2, 5-anhydro-D-mannitol (2,5-AM) treatment in nondeprived rats through indirect calorimetric measurements reveals that a sustained and significant reduction in respiratory quotient results from 2,5-AM treatment. The reduced respiratory quotient suggests that the proportion of total energy obtained from carbohydrate oxidation decreases, while that from fatty acid oxidation increases. The change in these metabolic factors does not affect the total metabolic rate, indicating the utility of 2,5-AM as a probe for the metabolic regulation of food intake.

The capacity of intraperitonal cholecystokinin COOH-terminal octapeptide (CCK)suppress food intake was studied in rats that were subjected to a control diet of ethanol (EtOH) in sucrose or sucrose alone for 6 months. Major dietary obesity was formed in EtOH and sucrose fed rats. In the EtOH group, the postprandial insulin levels were markedly enhanced, when layered to basal levels. The control of EtOH groups had markedly lower basal insulin levels than the sucrose group. The responsiveness to CCK-8 is enhanced by EtOH.

• Auditory brain stem responses measured over the life span of CBA/CaJ mice. • Tone burst ABR stimuli at 8, 12, 16, 24 & 32 kHz. • Age range from 79 to 1,085 days (3 to 36 months). • Significant hearing loss (increase in threshold) occurs at approximately 16-18 months, depending on frequency and sex. The inbred mouse strain CBA/CaJ is a frequently used animal model of age-related hearing loss in humans. These mice display significant hearing loss at a relatively advanced age, similar to most humans, with progressive loss of hearing as the mouse continues to age. While important descriptions of hearing loss in this mouse strain at multiple ages have previously been published, shortcomings persist in the data for hearing over the lifespan of the mouse. Therefore, we analyzed auditory brainstem response threshold data from records maintained by our research group to yield an extensive database of thresholds over nearly the entire life span of the CBA/CaJ mouse (from 79 to 1085 days). Data was collected from in-house bred mice of CBA/CaJ stock, initially from The Jackson Laboratory. Data was collected using BiosigRZ software and TDT System III hardware. Thresholds were routinely measured in conjunction with behavioral and electrophysiological experiments; only responses from baseline or experimentally naïve animals were analyzed. The resulting data set comprised 376 female mice and 441 males. At the lowest and highest frequencies (8 & 32 kHz), initial thresholds were just under 30 dB SPL and increased slowly until they were significantly different at 16-18 months compared to 1-3 months age, with the difference increasing over subsequent ages. At the middle frequencies (12 & 16 kHz), initial thresholds were just under 20 dB SPL and increased until they became different from initial at 16-18 months. At 24 kHz, initial thresholds were just above 20 dB and became different from initial at 13-16 months of age. The rate of change of thresholds with age were similar for all frequencies until about 30 months of age, when 32 kHz threshold changes lagged behind other frequencies. Generally, CBA/CaJ mice in our colony display relatively low thresholds until approximately 16 months of age, depending on frequency. After 16-18 months, thresholds become significantly worse. After approximately 20-22 months thresholds increase linearly with age. [ABSTRACT FROM AUTHOR]

We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We have reported that hyperglycemia is associated with reduction of neuronal size and reduced long-term spatial memory in the developing brain of streptozotocin diabetic (STZ-D) rats. We have also noted that recurrent hypoglycemia in age matched developing rat brains does not effect cell size or long-term memory. We have also shown that diabetes is associated with increased intracellular sorbitol and reduced taurine in the rat brain. Taurine is a cellular osmole regulator that counteracts the increased cellular osmoles associated with elevated sorbitol. Taurine is also a neurotrophic factor that stimulates neuronal growth. Objective: An aldose reductase inhibitor (sorbinil) was given to STZD rats to determine whether it would reduce polyol pathway activity and thereby increase intracellular taurine in the brain. Long-term spatial memory was also tested in these animals. Methods Male Wistar rats 4 weeks of age (100 g) were used. Control rats (10) were compared to STZ-D rats (10) and STZ-D rats receiving 65 mg/kg of oral sorbinil (STZ-D+S) (10) daily for 8 weeks. After 8 weeks of hyperglycemia each of the rats had long-term spatial memory tested using a radial-arm water maze. Brains were removed for measurement of sorbitol and taurine which were expressed as a function of tissue DNA. HbA1c was measured as an indicator of the degree of hyperglycemia. Results: The HbA1c levels of the STZ-D (8.2 ± 0.4), STZ-D+S (7.9 ± 0.3) rats were higher than controls (3.3 ± 0.0). Peripheral hyperglycemia was associated with increased brain sorbitol (0.14±0.02 vs 0.03±0.00lµg/ µg DNA) p<0.001, and reduced taurine (0.65±0.11 vs 1.3±0.09 mg/ µg DNA) p<0.001. Rats receiving Sorbinil had a reduction of cellular sorbitol (0.05 ± 0.001 vs 0.14 ± 0.02) p<0.01 and an increase in cellular taurine (1.26 ± 0.09 vs 0.65 ± 0.11) p<0.01. Long-term spatial memory following normal learning in the hyperglycemic animals was significantly impaired at 24 hours but was normal after receiving Sorbinil during 8 weeks of hyperglycemia. These animals also had normal cellular sorbitol and taurine. Conclusion: The reduced cognitive function associated with hyperglycemia in rats is corrected by inhibition of the polyol pathway and normalization of brain sorbitol and taurine without correcting the extracellular hyperglycemia. [ABSTRACT FROM AUTHOR]

Hyperinsulinemia activates brain Akt and PKC-λ/ι and increases Aβ 1–40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Aβ 1–40/42 , β-secretase activity was increased in insulin-resistant mice and monkeys. In insulin-resistant mice, inhibition of hepatic PKC-λ/ι sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously reversed increases in Akt, atypical protein kinase C (aPKC), β-secretase, and Aβ 1–40/42 , and restored acute Akt activation. However, 2 aPKC inhibitors additionally blocked insulin's ability to activate brain PKC-λ/ι and thereby increase β-secretase and Aβ 1–40/42 . Furthermore, direct blockade of brain aPKC simultaneously corrected an impairment in novel object recognition in high-fat-fed insulin-resistant mice. In neuronal cells and/or mouse hippocampal slices, PKC-ι/λ activation by insulin, metformin, or expression of constitutive PKC-ι provoked increases in β-secretase, Aβ 1–40/42 , and phospho-thr-231-tau that were blocked by various PKC-λ/ι inhibitors, but not by an Akt inhibitor. PKC-λ/ι provokes increases in brain β-secretase, Aβ 1–40/42 , and phospho-thr-231-tau. Excessive signaling via PKC-λ/ι may link hyperinsulinemia and other PKC-λ/ι activators to pathological and functional abnormalities in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT(2C) receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.