TRH protection against memory retrieval deficits is independent of endocrine effects

Stwertka, Steven A.; Vincent, George P.; Gamzu, Elkan; Macneil, Donald A.; Verderese, Anthony

doi:10.1016/0091-3057(92)90074-p

Cited by 20 publications

(11 citation statements)

References 30 publications

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“…The TSH was the only one that discriminates between OMU and OMI. The hypothalamus, by release of the thyrotropin releasing hormone (TRH), is a pivotal activator of the release of TSH in the pituitary gland, which in turn improves cognition in elderly subjects widely unrelated to the subsequent release of triiodotyronin (T3) and thyroxin (T4) in the thyroid gland (Stwertka et al, 1992;Chachamovitz et al, 2016;Szlejf et al, 2018). TSH could be associated with better performance in a variety of cognitive tests in aged humans (Beydoun et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Differences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory

Wackerlig

Köfeler

Korz

et al. 2020

Front. Aging Neurosci.

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Lipids play a major role for several brain functions, including cognition and memory. There is a series of work on individual lipids showing involvement in memory mechanisms, a concise lipidome was not reported so far. Moreover, there is no evidence for age-related memory decline and there is only work on brain of young vs. aging animals. Aging animals, however, are not a homogeneous group with respect to memory impairments, thus animals with impaired and unimpaired memory can be discriminated. Following recent studies of hippocampal lipid profiles and hypothalamus controlled hormone profiles, the aim of this study was to compare hypothalamic, lipidomic changes in male Sprague-Dawley rats between young (YM), old impaired (OMI) and old unimpaired (OMU) males. Grouping criterions for aged rats were evaluated by testing them in a spatial memory task, the hole-board. YMs were also tested. Subsequently brains were removed, dissected and hypothalami were kept at −80 • C until sample preparation and analysis on liquid chromatography / mass spectrometry (LC-MS). Significant differences in the amounts of a series of lipids from several classes could be detected between young and aged and between OMI and OMU. A large number of lipids were increased in OMI and a smaller number in OMU as compared to young rats. Differences of lipid ratios (log2 of ratio) between OMI and OMU consisted of glycerophosphocholines (

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Section: Discussionmentioning

confidence: 99%

Differences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory

Wackerlig

Köfeler

Korz

et al. 2020

Front. Aging Neurosci.

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“…In addition, it has pronounced CNS effects; it is a potent neuromodulator that facilitates cholinergic and monoaminergic neurotransmission and is an analeptic agent that also has trophic effects on neurons [73][74][75]. TRH also can enhance performance in cognitive behavioral models in animals suggesting its potential to treat cognitive disorders, including those associated with Alzheimer's disease [76][77][78]. However, endocrine effects, a short half-life and poor bioavailability are limitations for its use as a drug.…”

Section: A Trh Mimeticsmentioning

confidence: 99%

Conformational and Topographical Considerations in Designing Agonist Peptidomimetics from Peptide Leads

Hruby

2000

CMC

203

118

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The design of peptidomimetic ligands with agonist biological activities in vitro and in vivo has been challenging. Lofty goals have been set for this research including high potency, high receptor type selectivity, high stability in vitro and in vivo, and high efficacy in vitro and in vivo for agonists. A systematic stepwise strategy has been developed to accomplish these goals. These include determining the primary amino acid side chain residues required for molecular recognition and, in the case of agonist activity, those required for information transduction. In addition to determining the preferred backbone conformation which can serve as a template for the bioactive conformation (an alpha-helix, beta-turn, beta-sheet, etc.), a strategy has been developed to examine and determine the preferred side chain conformations in chi space (chi1, chi2, etc.). These include specific covalent and non-covalent constraints which can place the constrained side chains at highly preferred gauche (-), or gauche (+), or trans conformations. Examples are provided that illustrate this methodology and provide insight into the topographical requirements for ligand receptor interactions. Often, at this juncture one can obtain a quite precise 3D pharmacophore for the ligand, as well as high stability to agonist biodegradation and good bioavailability including the ability to cross membrane barriers. If a non-peptide ligand is desired, efforts are in progress to develop templates, and aspects of conformational design that permit assembling of all components necessary for molecular recognition and transduction. Here the proper choice of template that can place the key side chain residue in 3D space is still difficult, and thus only partial success has been achieved in terms of potent and selective ligands. A few of these approaches are presented and discussed in some detail.

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“…Administration of TRH to normal subjects results in a prompt increase of serum thyrotropin concentration. Stwertka et al (1) reported that TRH might play an important role in memory modulation and have therapeutic value in certain disease states in humans.…”

mentioning

confidence: 99%

Functional Characterization of 5-Oxoproline Transport via SLC16A1/MCT1

Sasaki

Futagi

Kobayashi

et al. 2015

Journal of Biological Chemistry

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TRH protection against memory retrieval deficits is independent of endocrine effects

Cited by 20 publications

References 30 publications

Differences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory

Differences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory

Conformational and Topographical Considerations in Designing Agonist Peptidomimetics from Peptide Leads

Functional Characterization of 5-Oxoproline Transport via SLC16A1/MCT1

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