Short-Term Memory Deficit Associates with miR-153-3p Upregulation in the Hippocampus of Middle-Aged Mice.

The early stages of ageing are a critical time window in which the ability to detect and identify precocious molecular and cognitive markers can make the difference in determining a healthy vs unhealthy course of ageing. Using the 6-different object task (6-DOT), a highly demanding hippocampal-dependent recognition memory task, we classified a population of middle-aged (12-month-old) CD1 male mice in Impaired and Unimpaired based on their short-term memory. This approach led us to identify a different microRNAs expression profile in the hippocampus of Impaired mice compared to Unimpaired ones. Among the dysregulated microRNAs, miR-153-3p was upregulated in the hippocampus of Impaired mice and appeared of high interest for its putative target genes and their possible implication in memory-related synaptic plasticity. We showed that intra-hippocampal injection of the miR-153-3p mimic in adult (3-month-old) mice is sufficient to induce a short-term memory deficit similar to that observed in middle-aged Impaired mice. Overall, these findings unravel a novel role for hippocampal miR-153-3p in modulating short-term memory that could be exploited to prevent early cognitive deficits in ageing.

Thalamo-hippocampal pathway regulates incidental memory capacity in mice.

Incidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1 h or 24 h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus leads to differences in incidental memory.

Influence of genetic type, live weight at slaughter and carcass fatness on fatty acid composition of subcutaneous adipose tissue of raw ham in the heavy pig.

The study aimed to assess some quality traits of the subcutaneous adipose tissue of raw ham for Parma production, obtained from 56 "traditional" Landrace×Large White (L×LW) and 56 Cotswold commercial hybrid (CH) pigs reared in the same conditions and slaughtered at an average live weight (l.w.) of about 165 kg. Further, the relationships between lipid composition, l.w. and carcass fatness were studied. Compared to the CH, the fatty tissue of L×LW pigs showed a lower water (6.33% vs. 7.35%, P<0.01) and a higher lipid (91.18% vs. 90.18%, P<0.01) content. CH lipids had higher polyunsaturated fatty acids (16.53% vs. 13.75%, P<0.01), and smaller saturated fatty acids (38.20% vs. 40.26%, P<0.01) content and a higher iodine value (69.69 vs. 65.22, P<0.01). An increased slaughter weight was associated with a lower degree of lipid unsaturation, but only the lowest weight class (<160 kg) showed a significant difference compared to the other two classes (⩾160<170 and ⩾170 kg). Regardless of genetic type or l.w. class, an increase in backfat thickness is associated with an increase in saturated and monounsaturated fatty acids and a remarkable reduction in polyunsaturated content.

Distinct pattern of c-fos mRNA expression after systemic and intra-accumbens amphetamine and MK-801.

Pharmacological manipulation of both dopamine and glutamate systems affects motor responses in laboratory animals. The two systems, however, seem to act in opposite ways, since direct or indirect activation of dopamine receptors induces similar stimulatory effects to those seen following blockade of N-methyl-D-aspartate receptors. In the present study we compared the pattern of c-fos activation induced by systemic and intra-accumbens administration of the non-competitive N-methyl-D-aspartate antagonist MK-801 and the indirect dopamine agonist amphetamine. Systemic MK-801 induced c-fos mRNA expression in the motor cortex and preferentially in the motor thalamus, i.e. ventrolateral nucleus. Systemic amphetamine, on the other hand, enhanced c-fos mRNA expression in the shell of the accumbens and in limbic thalamic nuclei such as the anteroventral and anterodorsal nuclei. The main effect observed after intra-accumbens administrations of either drug was enhanced c-fos expression in the thalamus, somewhat similar to what seen following systemic administration. In fact also in this case there was a preferential activation of the limbic thalamus by amphetamine and the motor thalamus by MK-801. The present results confirm that different neural substrates underlie behavioral effects induced by systemic administrations of N-methyl-D-aspartate receptor antagonists and dopamine agonists. Further they suggest that intra-accumbens manipulation of the two neural systems could affect different efferent pathways from this structure activating different thalamic targets.

Locomotor activity induced by the non-competitive N-methyl-D-aspartate antagonist, MK-801: role of nucleus accumbens efferent pathways.

We have recently shown that focal administration of dizocilpine hydrogen maleate (MK-801, a non-competitive N-methyl-D-aspartate antagonist) within the nucleus accumbens increases locomotor activity in a dopamine-independent manner. The purpose of this study was to investigate the neural network underlying locomotor stimulation induced by N-methyl-D-aspartate receptor blockade in the accumbens. In the first experiment, we examined the effect of different doses (1, 5 and 25 nmol) of the active and inactive enantiomers of the N-methyl-D-aspartate antagonist, (+)- and (-)-MK-801, respectively, focally administered in the nucleus accumbens. Only the active enantiomer induced a significant increase in locomotor activity; furthermore, the effect induced by the two highest doses of (+)-MK-801 was significantly different from that induced by (-)-MK-801. In the second part of the study, we performed ibotenic acid lesions to the major output nuclei of the accumbens, the ventral pallidum, mediodorsal thalamus, ventrolateral/ventromedial thalamus and pedunculopontine tegmental nucleus, to observe their effect on locomotor activity induced by focal (+)-MK-801 (25 nmol) administration into the accumbens. None of the lesions had any effect on spontaneous locomotor activity. Hyperactivity induced by accumbens MK-801 administrations was unaffected by ibotenic acid lesions of the pedunculopontine tegmental nucleus, while lesions of the mediodorsal thalamus induced only a partial inhibition. In contrast, ibotenic acid lesions of the ventral pallidum and ventrolateral/ventromedial thalamus completely blocked the motor response induced by accumbens MK-801. These data indicate that the intact mediodorsal thalamus, which has been proposed as a part of the loop that relays accumbens information to the prefrontal cortex, does not seem to be a structure of primary importance in MK-801 locomotor activity. On the contrary, the motor nuclei of the thalamus appear to play a more relevant role, suggesting that different neural substrates may mediate dopamine and glutamate functional output from the nucleus accumbens.

The effect of dietary supplementation of vitamins C and E on the α-tocopherol content of muscles, liver and kidney, on the stability of lipids, and on certain meat quality parameters of the longissimus dorsi of rabbits.

The trial was carried out to investigate the effects of adding to the diet of rabbits vitamin E (40; 300; 500 ppm) and C (0; 500 ppm), on vitamin E deposition in the muscles and organs, on the oxidative stability of muscular lipids, and on various meat quality characteristics. The α-tocopherol content in muscles and organs was roughly doubled by feeding the highest levels of vitamin E; it was also increased by giving 500 ppm of vitamin C, but only in those muscles of rabbits receiving 40 ppm of vitamin E. The α-tocopherol content in tissues was negatively correlated with TBARS values of the longissimus dorsi (LD) at days 6 and 8 post mortem (p.m.). Five hundred parts per million (ppm) of vitamin C increased lipid stability of the LD at both 6 and 8 days p.m., though its effect was significant only with 40 ppm of vitamin E. Moreover, 500 ppm of vitamin C resulted in the lowest L(*) and highest pH values at all p.m. times, when the dietary vitamin E was equal to 40 ppm, and in the highest L(*) and lowest pH values when the vitamin E was equal to 300 ppm. Conversely, weight losses of the LD were the lowest, at days 6 and 8 p.m., in the group fed the highest levels of both vitamins.

Nucleus accumbens dopamine receptors in the consolidation of spatial memory.

Nucleus accumbens dopamine is known to play an important role in motor activity and in behaviours governed by drugs and natural reinforcers, as well as in non-associative forms of learning. At the same time, activation of D1 and D2 dopamine receptors has been suggested to promote intracellular events related to neural plasticity. Therefore, in this study we wished to investigate the role of the two classes of dopamine receptors within the nucleus accumbens on the consolidation of spatial information. On day 1, CD1 male mice were placed in an open field containing five different objects and, immediately after three sessions of habituation, the animals were focally injected within the nucleus accumbens with either the D1 antagonist SCH 23390 (12.5, 25 or 50 ng/side), or the D2 antagonist sulpiride (25, 50, 75 or 100 ng/side). Twenty-four hours later the ability of mice to discriminate an object displacement was assessed. Both the D1 and the D2 antagonists impaired the ability of mice to detect the spatial change. If the highest doses of the two antagonists were injected 2 h after the end of the last of the habituation sessions, no effect was observed in the reactivity to spatial change examined 24 h later. These data demonstrate that activation of both D1 and D2 receptors within the accumbens is necessary in the early stages of the consolidation of spatial information. The data are discussed in terms of involvement of nucleus accumbens dopamine in information processing in the absence of explicit reinforcers.