Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rat thhe perforant pathways from the entorhinal area normally innervate the fascia dentata only ipsilaterally. However, unilateral ablation of the entorhinal area (deentorhination) induces the formation of an anomalous crossed projection from the intact contralateral entorhinal area to the septal portion of the deafferented fascia dentata. After deentorhination of rats aged 1-30 days the organization of this projection was analyzed (a) by producing secondary lesions in the intact entorhinal area of perforant paths and observing the results anterograde degeneration with Fink-Heimer silver impregnation techniques, and (b) by staining with Timm's sulfide silver method whichmakes the terminal fields of afferent systems stand out in different tones of colors. Both methods showed the crossed entorhino-dentate projection to consist of two separable components. They were named the crossed medial perforant path and the crossed lateral perforant path, corresponding to their similarity in origin, dendritic localization of termination and Timm stainability to the ordinary, uncrossed medial and the lateral perforant pathways (MPP and LPP) which arise in the medial and lateral parts of the entorhinal cortex, respectively. Similarly induced crossed projections were demonstrated to the subcallosal continuation of fascia dentata, the fasciola cinerea. The heaviest terminal field of the crossed entorhino-dentate projection which was found in the most rostral and medial parts of the deafferented fascia dentata correlated with a lack of expected aberrant extension into theMPP and LPP terminal zones of commissural and ipsilateral hippocampodentate fibers. In Fink-Heimer preparations there was little variation in the distribution of the aberrant crossed sustems over the range of ages studied although the chronic operations performed earliest postnatally (5 days) tended to produce the heaviest representation. This latter observation appeared consistent with changes in the Timm staining pattern of the deafferented fascia dentata, since with an increase in age at the primary lesion from 5 to 14 days there was no increase in the spread into the fascia dentata of Timm stainable axon ter minals from CA3, interpreted as a sign of fewer crossed entorhinal afferents succeeding in a presumable competition with the CA3-derived system for available terminal space.
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PMID:Crossed pathways from the entorhinal area to the fascia dentata. II. Provokable in rats. 113 28

The mixed CCK antagonist N-(3-oxo- 2,3-dihydro-1H-pyrazol-4-yl)-indole-carboxamide MPP with a binding affinity of 25nM /20nM and the CCK1 selective 3-oxo-1,2-diphenyl-2,3-dihydro-1Hpyrazol- 4-yl)-N'-phenyl-urea MPM (IC50 = 25nM) represent the best two compounds of an amide and a urea pyrazoline series, which were previously evaluated in mice (Part 1) for their CNS activity. The long term in vivo and in vitro evaluation is described in this part. Stress was induced for a 4 week period daily. A dose of 0.5 mg/kg of MPP and MPM showed a significant antidepressant effect in the foced swim test in rats, which was in enhanced within a 4 week test period. The mixed CCK antagonist MPM only occurred anxiolytic properties in the elevated X-maze in rats at a 0.5 mg/kg dose. For the stress induced rats, the MPP and MPM treatment reversed the effects of stress on the dendritic atrophy in hippocampal CA3 pyramidal neurons. A reduction of organ weight was reversed for the adrenal gland, when the animals were treated with the CCK antagonists MPP and MPM over a period of 4 weeks.
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PMID:Part 2. Long term in vivo/in vitro evaluation of the Cholecystokinin antagonists: N-(5-methyl-3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-N'-phenylurea MPP and carboxamide MPM. 2250 44

Non-selective inhibition of histone deacetylases (HDACs), enzymes that remove acetyl groups from histone core proteins, enhances cognition and NMDAR-dependent long-term potentiation at hippocampal CA3-CA1 synapses. It is not known whether this is a general mechanism by which HDACs modulate plasticity at other hippocampal synapses. Furthermore, it has yet to be tested whether HDAC inhibition can reverse deficits in synaptic plasticity in disease models. Here, we investigated whether inhibition of HDACs, and specifically HDAC3, a class I HDAC isoform known to negatively regulate hippocampus-dependent learning and memory, enhances LTP at medial perforant path-dentate granule cell (MPP-DGC) synapses in wild-type and Fragile X (Fmr1-/y) mice, a model with known LTP deficits at this synapse. The non-selective HDAC inhibitor trichostatin A (TSA) significantly increased the magnitude of LTP at MPP-DGC synapses in wild-type mice, similar to reports at CA3-CA1 synapses. The enhancement of LTP was mimicked by selective HDAC3 inhibition, implicating a role for this isoform in the negative regulation of synaptic plasticity. However, HDAC3 inhibition was completely ineffective in reversing the deficit in LTP at MPP-DGC synapses in slices from Fmr1-/y mice, and in fact, HDAC3 inhibition was unable to induce any improvement whatsoever. These findings indicate that the enhancing effect of HDAC3 inhibition on LTP in wild-type mice requires FMRP, revealing a novel role for FMRP in hippocampal plasticity.
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PMID:Increased long-term potentiation at medial-perforant path-dentate granule cell synapses induced by selective inhibition of histone deacetylase 3 requires Fragile X mental retardation protein. 2495 40

Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides support for this model as a valuable preclinical tool in elucidating pathological mechanisms of early synapse dysfunction in AD.
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PMID:Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model. 3004 46