Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms

Ahshin-Majd, Siamak; Zamani, Samira; Kiamari, Taktom; Kiasalari, Zahra; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

doi:10.1016/j.peptides.2016.10.008

Cited by 61 publications

(36 citation statements)

References 98 publications

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“…Second transition latency of diabetic rats treated with piracetam is also longer than those of untreated diabetic rats ( p < 0.001). These findings indicated that diabetes caused impairments in the emotional learning and memory performances of rats in parallel with the previous literature [38,39]. In addition, agomelatine treatment reversed these detrimental effects with a comparable efficacy to piracetam.…”

Section: Resultssupporting

confidence: 89%

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The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Can

Üçel

Özkay

et al. 2018

IJMS

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Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials.

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Section: Resultssupporting

confidence: 89%

“…First, the contours of the dentate gyrus and the CA1–3 subfields were delineated under low magnification (2.5×) (Figure 10A). Then, approximately 60% of the outlined region was analyzed by systematic random sampling [38]. All neuronal profiles in every 8th sections were counted while using an oil-immersion lens (Figure 10B) [68].…”

Section: Methodsmentioning

confidence: 99%

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Can

Üçel

Özkay

et al. 2018

IJMS

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“…In agreement with previous results, showing the ability of carnosine to indirectly counteract oxidative stress by enhancing the expression of members of the endogenous antioxidant system, including HO-1 and Nrf2 [56][57][58], under our experimental conditions we found that carnosine up-regulated both Nrf2 and, particularly, its downstream product HO-1 (Figure 8). Since the activity of HO-1 has been addressed as one of the main actors in the defense system towards oxidative/nitrosative stress [10,[59][60][61][62], it is presumable that the carnosine-mediated positive HO-1 modulation contributes in part to the generalized decrease in metabolic indicators of sustained oxidative/nitrosative stress (sum of nitrite + nitrate, MDA; Figures 2 and 6).…”

Section: Discussionsupporting

confidence: 93%

“…This peculiar carnosine activity might certainly be of relevance for its potential therapeutic applications. It is well-known that excessive levels of iNOS-induced NO in macrophages are closely associated with different inflammatory diseases [57,58] and that when overproduced, NO reacts with superoxide ion generating peroxynitrite [22]. Carnosine, by accelerating NO degradation into NO 2 − , might efficiently decrease the levels of one of the substrates needed for the formation of peroxynitrite, diminishing risks of peroxynitrite-mediated damages to fundamental macromolecules [59].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine

Fresta

Fidilio

Lazzarino

et al. 2020

IJMS

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Carnosine is a natural endogenous dipeptide widely distributed in mammalian tissues, existing at particularly high concentrations in the muscles and brain and possesses well-characterized antioxidant and anti-inflammatory activities. In an in vitro model of macrophage activation, induced by lipopolysaccharide + interferon-gamma (LPS + IFN-γ), we here report the ability of carnosine to modulate pro-oxidant and pro-inflammatory activities of macrophages, representing the primary cell type that is activated as a part of the immune response. An ample set of parameters aimed to evaluate cytotoxicity (MTT assay), energy metabolism (HPLC), gene expressions (high-throughput real-time PCR (qRT-PCR)), protein expressions (western blot) and nitric oxide production (qRT-PCR and HPLC), was used to assess the effects of carnosine on activated macrophages challenged with a non cytotoxic LPS (100 ng/mL) + IFN-γ (600 U/mL) concentration. In our experimental model, main carnosine beneficial effects were: (1) the modulation of nitric oxide production and metabolism; (2) the amelioration of the macrophage energy state; (3) the decrease of the expressions of pro-oxidant enzymes (Nox-2, Cox-2) and of the lipid peroxidation product malondialdehyde; (4) the restoration and/or increase of the expressions of antioxidant enzymes (Gpx1, SOD-2 and Cat); (5) the increase of the transforming growth factor-β1 (TGF-β1) and the down-regulation of the expressions of interleukins 1β and 6 (IL-1β and IL-6) and 6) the increase of the expressions of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1). According to these results carnosine is worth being tested in the treatment of diseases characterized by elevated levels of oxidative stress and inflammation (atherosclerosis, cancer, depression, metabolic syndrome, and neurodegenerative diseases).

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“…AD is not the result of a single etiology (42). Multiple mechanisms may lead to cognitive impairment and involve cellular injury from β-amyloid (Aβ), tau, excitotoxicity, mitochondrial damage, acetylcholine loss, astrocytic cell injury, oxidative stress, and cellular metabolic dysfunction with DM (14, 51–57). Yet, there is a growing arsenal of novel therapeutic strategies directed against AD and other neurodegenerative disorders that include circadian rhythm clock genes (9), non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs) (56, 58, 59).…”

Section: Novel Nervous System Strategiesmentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

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BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

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Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms

Cited by 61 publications

References 98 publications

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

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