Does the human leukaemia differentiation factor fragment HLDF6 improve memory via brain DNA and protein synthesis?

Abstract

The novel human differentiating factor peptide fragment HLDF6 (Thr-Gly-Glu-Asn-His-Arg) was synthesized and purified. HLDF6 (0.1mg/kg i.p. but not 1mg/kg i.p.) improved not only long-term (24h) memory in adult rats in the water maze behavioural paradigm but also performance in the delayed matching-to-position (DMTP) task (0.3 and 1.0 but not 0.1mg/kg i.p). Hence, HLDF6 not only enhanced allocentric spatial learning and reference memory (water maze) but also improved temporal, spatial and working memory processes in the DMTP behavioural paradigm. Immunoreactivity blotting analysis of HLDF (the protein precursor of HLDF6) was performed and the following rank order of visual intensities from brain structures was noted: hippocampus cerebral cortex cerebellum hypothalamus striatum. Subsequently, we found that the highest absolute levels of HLDF were expressed in the hippocampus and cerebral cortex as detected by ELISA. We also demonstrated that HLDF6 enhanced [(3)H]-thymidine and [(14)C]-leucine incorporation into whole brain and hippocampal homogenates (maxima occurring within the range 10 (-12)-10 (-6) M) suggesting that this hexapeptide promoted de novo DNA and protein biosynthesis. We discuss this data in terms of their implications for links with other integrative metabolic pathways involving immediate early gene activation which may underpin a potential application for HLDF6 in limiting memory impairments associated with neurodegenerative diseases.

Comparative study of carboxylate and amide forms of HLDF-6 peptide: Neuroprotective and nootropic effects in animal models of ischemic stroke

“…In experimental models of clinical pathologies-Alzheimer's disease (AD) and IS-the peptide was demonstrated to alleviate pronounced cognitive de iciency and promote memory retrieval. As demonstrated [9,10] by histological studies of experimental animal brain slices, the damaged area of hippocampal neurons decreased almost three-fold upon intramuscular injection of the peptide. In addition, HLDF-6 did not modify the haemodynamic indices, nor did it disrupt motion activity or motor coordination in the animals [11].…”

The Specific Effect of the HLDF-6 Nootropic Peptide on the Activity of Interneurons of the Snail Defensive Behavior

“…Последовательность нанесения стимулов -химического раздражения головы, тактильного раздражения ноги и головы -меняли в каждом опыте. В работах, выполненных нами ранее [3], показано, что стабильность синаптических ответов у нейронов сохраняется на протяжении 5-6 ч эксперимента. Так как у некоторых нейронов генерация потенциалов действия препятствовала измерению площади мВПСП, ответы на раздражители регистрировали при гиперполяризации мембраны до 80 мВ.…”

“…Ранее мы обнаружили [6], что в процессах синаптической пластичности в сенсорных входах нейронов ЛПл1 от хеморецепторов головы избирательно участвуют цАМФ и зависимые от него транскрипционные факторы немедленного раннего гена С/ЕВР (CAAT/enhancer binding protein). Эти факты подтверждают предположение о возможности влияния HLDF-6 на активность ранних генов [3].…”

“…В опытах с использованием различных экспериментальных моделей животных (водный лабиринт Морриса, тест пассивного избегания, тест распознавания объекта) обнаружено, что центральное и системное введение пептида здоровым животным способствует формированию и хранению долговременной памяти [1]. Показано, что пептид устранял выраженный когнитивный дефицит в экспериментальных моделях клинической патологии и вносил вклад в восстановление  МЕДИЦИНСКИЕ НАУКИ  нарушенной памяти [3]. Пептид HLDF-6 обладает высокой анксиолитической активностью.…”

Experimental model of hemorrhagic stroke: Rabbit immunization with HL-60 promyelocytic cell differentiation factor

“…Two active fragments of HLDF are identified: six-member peptide fragment (HLDF-6) completely retaining differentiating activity of the initial protein and possessing antiapoptotic and cell-protective properties and eightmember peptide (HLDF-8) capable of inducing programmed cell death [1,2]. HLDF is present in mammalian and human blood and nervous system, while the peptide fragments of this protein are essential for cognitive functions [14]. Hemodynamic activities of differentiation factor peptides HLDF-8 and HLDF-24 modifying arterial pressure and heart rate were demonstrated [4].…”