Biomedical subjects

Daniel Alkon

Publications and source records attributed to Daniel Alkon.

3 recordsLinked to original sources

PubMed2006

Cholesterol-enriched diet affects spatial learning and synaptic function in hippocampal synapses.

The aim of the present study was to determine the effect of a cholesterol-rich diet on learning performance and monitor possible related changes in synaptic function. To this purpose, we compared controls with rats fed with a cholesterol-enriched diet (CD). By using a Morris water-maze paradigm, we found that CD rats learned a water-maze task more quickly than rats fed with a regular diet (RD). A longer period of this diet tended to alter the retention of memory without affecting the improvement in the acquisition of the task. Because of the importance of the hippocampus in spatial learning, we hypothesized that these behavioral effects of cholesterol would involve synaptic changes at the hippocampal level. We used whole-cell patch-clamp recording in the CA1 area of a hippocampal rat slice preparation to test the influence of the CD on pre- and postsynaptic function. CD rats displayed an increase in paired-pulse ratio in both glutamatergic synapses (+48 +/- 9%) and GABAergic synapses (+41 +/- 8%), suggesting that the CD induces long-lasting changes in presynaptic function. Furthermore, by recording NMDA-receptor-mediated currents (I(NMDA)) and AMPA-receptor-mediated currents (I(AMPA)) in the same set of cells we found that CD rats display a lower I(NMDA)/I(AMPA) ratio (I(NMDA)/I(AMPA) = 0.75 +/- 0.32 in RD versus 0.10 +/- 0.03 in CD), demonstrating that cholesterol regulates also postsynaptic function. We conclude that a cholesterol-rich diet affects learning speed and performance, and that these behavioral changes occur together with robust, long-lasting, synaptic changes at both the pre- and postsynaptic level.

Aging↗

PubMed2006

Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice.

The cbl-b gene is a member of the cbl protooncogene family. It encodes a protein with multiple domains, which can interact with other proteins in a variety of signaling pathways. The functions of cbl family genes in the brain are unknown. In this report, we used genetic, immunohistochemical, behavioral, and electrophysiological approaches to study the role of cbl-b in learning and memory. Cbl-b null mice developed normally and had no abnormalities in their locomotor performance. In spatial learning and memory studies, cbl-b null and WT mice performed similarly during training. To test memory retention, two probe trials were used. cbl-b null mice performed slightly better 1 day after training. However, in the probe trial 45 days after training, the cbl-b null group showed significantly higher memory retention than WT mice, suggesting an enhancement of long-term memory. Using electrophysiological approaches, we found there was enhanced paired-pulse facilitation in the Schaffer Collateral-CA1 glutamatergic synapses of the cbl-b null mice. On the other hand, there was no difference in long-term potentiation between the two groups of mice. In summary, we provide evidence that (i) cbl-b protein is concentrated in the synaptic regions of CA1, CA3, and the dentate gyrus of the hippocampus; (ii) cbl-b null mice have enhanced long-term memory; and (iii) cbl-b null mice show an enhancement in short-term plasticity. These results indicate that cbl-b is a negative regulator of long-term memory, and its neuronal mechanism regulates synaptic transmission in the hippocampus.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Gene expression profiles of heme oxygenase isoforms in the rat brain.

In the last decade the heme oxygenase (HO) system has been strongly highlighted for its potential significance in maintaining cellular homeostasis. Nevertheless the physiological relevance of the three isoforms cloned to date, HO-1, HO-2 and HO-3, and their reciprocal interrelation have been poorly understood. In the brain the HO system has been reported to be very active and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. To discriminate the regional and cellular distribution of HO isoforms in the CNS, we have developed a real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) protocol. With this highly sensitive methodology we have assessed for the first time the expression of all known HO isoform mRNAs in different rat brain areas. Although they presented a highly dissimilar range of expression, with HO-2>HO-1>HO-3, all three HO isoform transcripts demonstrated high level of expression in the cerebellum and the hippocampus, showing in a different scale, a strikingly parallel distribution gradient. We have also quantified the expression of HO mRNAs in primary culture of cortical neurons and type I astrocytes. While HO-1 and HO-2 were detected in both cellular types, HO-3 transcript was uniquely found in astrocytes. To further investigate the regional brain expression of this elusive and poorly studied isoform, we have performed in situ hybridization using an HO-3 specific riboprobe. HO-3 mRNA was expressed mainly in hippocampus, cerebellum and cortex. The initial elucidation of HO isoforms distribution should facilitate further research on their pathophysiological role in the nervous system.

Animals↗