Beneficial actions of prothymosin alpha-mimetic hexapeptide on central post-stroke pain, reduced social activity, learning-deficit and depression following cerebral ischemia in mice

• Published in: Peptides (New York, N.Y. : 1980) Vol. 126; p. 170265
• Main Authors: Sasaki, Keita, Halder, Sebok Kumar, Matsunaga, Hayato, Ueda, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020
• Subjects: Animals; Brain Ischemia - chemically induced; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Brain Ischemia - psychology; Cerebral ischemia; Depression; Depression - drug therapy; Depression - etiology; Depression - pathology; Learning; Male; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - pathology; Memory-Learning deficit; Mice; Mice, Inbred C57BL; Neuroprotective Agents - pharmacology; Pain - drug therapy; Pain - etiology; Pain - pathology; Peptide Fragments - pharmacology; Post-Stroke pain; Protein Precursors - pharmacology; Prothymosin alpha-memetic hexapeptide; Social activity; Stroke - chemically induced; Stroke - drug therapy; Stroke - pathology; Stroke - psychology; Thymosin - analogs & derivatives; Thymosin - pharmacology; Tissue Plasminogen Activator - toxicity; i.v; BCCAO; Social activity; Cerebral ischemia; tPA; Memory-Learning deficit; Post-Stroke pain; Depression; PIT; P6Q; Prothymosin alpha-memetic hexapeptide
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2020.170265

•Prothymosin alpha-mimetic hexapeptide P6Q improves late tPA-induced post-stroke pain.•P6Q inhibits late tPA-induced loss of social activity after focal cerebral ischemia.•P6Q improves global cerebral ischemia-induced impairment of cognitive function.•P6Q suppresses global cerebral ischemia-induced depression-like behavior.•Thus, P6Q could be a beneficial candidate to prevent post-stroke prognostic symptoms. Prothymosin alpha (ProTα)-mimetic hexapeptide (amino acid: NEVDQE, P6Q) inhibits cerebral or retinal ischemia-induced behavioral, electrophysiological and histological damage. P6Q also abolishes cerebral hemorrhage induced by ischemia with tissue plasminogen activator (tPA). In the present study we examined the beneficial effects of P6Q on other post-stroke prognostic psychology-related symptoms, which obstruct the motivation toward physical therapy. Intravenous (i.v.) administration with tPA (10 mg/kg) at 6 h after photochemically induced thrombosis (PIT) in mice resulted in bilateral central post-stroke pain in thermal and mechanical nociception tests and loss of social activity in the nest building test, both of which were significantly blocked by P6Q (30 mg/kg, i.v.) given at 5 h after PIT. P6Q (30 mg/kg, i.v.) also improved the memory-learning deficit in the step-through test and depression-like behavior in the tail suspension test when it was given 1 day after bilateral common carotid arteries occlusion (BCCAO) in mice. Thus, these studies suggest that P6Q could be a promising candidate to prevent negative prognostic psychological symptoms following focal and global ischemia.