Antidepressant-Like and Antistress Effects of the ACTH(4-10) Synthetic Analogs Semax and Melanotan II on Male Rats in a Model of Chronic Unpredictable Stress

Article

Author: Myasoedov, Nikolai F. ; Levitskaya, Natalia G ; Dolotov, Oleg V. ; Glazova, Natalya Yu ; Kamensky, Andrey A. ; Yatsenko, Ksenia A. ; Yatsenko, Ksenia A ; Kamensky, Andrey A ; Levitskaya, Natalia G. ; Inozemtseva, Ludmila S. ; Inozemtseva, Ludmila S ; Myasoedov, Nikolai F ; Dolotov, Oleg V ; Glazova, Natalya Yu. ; Grivennikov, Igor A ; Grivennikov, Igor A.

Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback. Here, we investigated whether noncorticotropic synthetic analogs of the ACTH(4-10) fragment, ACTH(4-7)-Pro-Gly-Pro (Semax) and Ac-Nle4-cyclo[Asp5-His6-D-Phe7-Arg8-Trp9-Lys10]ACTH(4-10)-NH2 (Melanotan II (MTII), a potent agonist of melanocortin receptors), have potential antidepressant activity in a chronic unpredictable stress (CUS) rat model of depression. Stressed and control male adult Sprague-Dawley rats received daily intraperitoneal injections of saline or a low dose (60 nmol/kg of body weight (BW)) of Semax or MTII. Rats were monitored for BW and hedonic status, as measured in the sucrose preference test. We found that chronic treatment with Semax and MTII reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF. In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected. Our findings show that in the CUS paradigm, systemically administered ACTH(4-10) analogs Semax and MTII exert antidepressant-like effects on anhedonia and hippocampal BDNF levels, and attenuate markers of chronic stress load, at least in male rats. The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.

16 Feb 2022·ACS Chemical NeuroscienceQ3 · MEDICINE

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Q3 · MEDICINE

Article

Author: Attanasio, Francesco ; Naletova, Irina ; Sciacca, Michele F.M. ; Giuffrida, Maria Laura

Alzheimer's disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu²⁺ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu²⁺ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu²⁺ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu²⁺ complexes but also has anti-aggregating and protective properties especially in the presence of Cu²⁺. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu²⁺ complexes.

01 Jan 2022·Voprosy kurortologii, fizioterapii i lechebnoi fizicheskoi kul'tury

Results of the application of complex physiotherapeutic neurostimulation in optical neuropathies of various genesis

Article

Author: Elfimov, M A ; Yusef, Yu ; Sheludchenko, V M ; Korchazhkina, N B ; Dragon, A K ; Makarova, M A ; Kosova, J V

Optical neuropathies (ON) are the outcome of many diseases of various origins. The main ones are classified as inflammatory, vascular and traumatic ON. ON lead to subatrophy of the optic nerve, but even after the completion of treatment, it is possible to improve visual functions by using physiotherapeutic means of ophthalmic rehabilitation.OBJECTIVETo evaluate the effectiveness of complex physiotherapeutic neuro-ophthalmostimulation in case of ON of vascular origin.MATERIAL AND METHODSThe study included 60 patients (120 eyes) with a verified diagnosis of optic neuropathy of vascular origin, who were divided into 2 groups comparable in age, gender and anatomical and functional characteristics: the main group of 30 patients (60 eyes) and the control group - 30 patients (60 eyes), including 24 men and 36 women, mean age was 66.2±4.1 years, disease duration was 4.1±1.7 years. All patients underwent courses of conservative treatment with vitamins according to the available ophthalmological standards, repeating them 1-2 times a year, the last of which was six months before the present study. Physiotherapy courses and patients did not pass. 20 healthy volunteers were taken to create basic indicators of the «norm» of the applied research methods. Patients of the main group used a set of procedures: transcranial magnetic electrical stimulation, endonasal electrophoresis with the drug neuroprotector Semax 0.1%, oxybaric chamber and acupuncture. Patients in the control group were prescribed basic therapy, including taking the vitamin complex BEROCCA for 3 months. Breakpoints: before treatment and at times: 1st week, 12 weeks and 24 weeks after the course of treatment, according to the standard recommendations for international multicenter studies. The following were assessed: visual field boundaries (dilation meridians; in deg.), light sensitivity (MS, MD; in dB), indicators of the state of the retinal ganglion layer (GCS thickness, volume loss): Avg CCG (in µm), FLV, GLV (in %).RESULTSWhen evaluating the results in patients of the main group who received complex neurostimulation, the therapeutic efficacy in a week after the end of treatment was 94%, in 12 weeks - in 88% and in 24 weeks - 83%, while in patients of the control group for all studied indicators showed only a positive trend and therapeutic efficacy did not exceed 30-42%.CONCLUSIONUnder the influence of the developed neurostimulating complex, the activity of nerve cells objectively increases, leading to a significant increase in the boundaries of the field of view and light sensitivity and a decrease in global losses of the retinal ganglion complex and optic nerve.

100 Deals associated with Semax

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