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Nicotinamide and Nicotinoyl-Gamma-Aminobutyric Acid as Neuroprotective Agents Against Type 1 Diabetes-Induced Nervous System Impairments in Rats

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Abstract

Diabetes is a multifunctional chronic disease that affects both the central and/or peripheral nervous systems. This study assessed whether nicotinamide (NAm) or conjugate of nicotinic acid with gamma-aminobutyric acid (N-GABA) could be potential neuroprotective agents against type 1 diabetes (T1D)-induced nervous system impairments in rats. After six weeks of T1D, induced by streptozotocin, nonlinear male Wistar rats were treated for two weeks with NAm (100 mg/kg, i. p.) or N-GABA (55 mg/kg, i. p.). Expression levels of myelin basic protein (MBP) were analyzed by immunoblotting. Polyol pathway parameters of the sciatic nerves were assessed spectrophotometrically, and their structure was examined histologically. NAm had no effect on blood glucose or body weight in T1D, while N-GABA reduced glucose by 1.5-fold. N-GABA also increased MBP expression by 1.48-fold, enhancing neuronal myelination, while NAm showed no such effect. Activation of the polyol pathway was observed in the T1D sciatic nerves. Both compounds decreased sorbitol content and aldose reductase activity, thereby alleviating changes similar to primary degeneration in the sciatic nerves and preventing peripheral neuropathy development. These results demonstrate that NAm and, more notably, N-GABA may exert neuroprotective effects against T1D-induced nervous system impairments by increasing MBP expression levels, improving myelination processes in the brain, inhibiting the polyol pathway, and partially restoring morphometric parameters in the sciatic nerves. This suggests their potential therapeutic efficacy as promising agents for the prevention of T1D-induced nervous system alterations.

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

BBB:

Blood-Brain Barrier

BNB:

Blood-Nerve Barrier

CNS:

Central Nervous System

DPN:

Diabetic Peripheral Neuropathy

GABA:

Gamma-Aminobutyric Acid

GFAP:

Glial Fibrillary Acidic Protein

i.p.:

Intraperitoneal

MBP:

Myelin Basic Protein

NAm:

Nicotinamide

NAD+ :

Nicotinamide Adenine Dinucleotide

NADP+ :

Nicotinamide Adenine Dinucleotide Phosphate

NADH:

Nicotinamide Adenine Dinucleotide Hydrogen

NADPH:

Nicotinamide Adenine Dinucleotide Phosphate Hydrogen

N-GABA:

Nicotinoyl-GABA

Nf-L:

Neurofilament Light Chain

PARP-1:

Poly-ADP-Ribose Polymerase-1

PNS:

Peripheral Nervous System

SD:

Standard Deviation

SIRT1:

NAD-dependent protein deacetylase sirtuin-1

SIRT2:

NAD-dependent protein deacetylase sirtuin-2

SEM:

Scanning Electron Microscopy

STZ:

Streptozotocin

T1D:

Type 1 Diabetes

T2D:

Type 2 Diabetes

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Funding

This work was funded by the budget program of National Academy of Sciences of Ukraine.

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Authors and Affiliations

  1. Department of Vitamin and Coenzyme Biochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine

    Tamara Kuchmerovska & Tetiana Tykhonenko

  2. Department of Medical Biochemistry and Molecular Biology, Bogomolets National Medical University, Kyiv, Ukraine

    Lesya Yanitska

  3. Department of Histology and Embryology, Bogomolets National Medical University, Kyiv, Ukraine

    Serhiy Savosko

  4. I. Horbachevsky Ternopil National Medical University, Ministry of Health of Ukraine, Ternopil, Ukraine

    Iryna Pryvrotska

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Contributions

T.K. wrote the main manuscript text and did conceptualization, methodology, reviewing & editing. T.T. prepared Fig. 1 and did investigation, methodology, visualization and data curation. S.S. prepared Fig. 2 and did methodology, visualization and data curation. L.Y. and I.P. did investigation, visualization and data curation. All authors helped to critically revise the intellectual content of the manuscript and approved the final submission.

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Correspondence to Tamara Kuchmerovska.

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All animal experiments were carried out in accordance with the Directive 2010/63/ EU and approved by the Animal Care and Use Committee of Palladin Institute of Biochemistry, NAS of Ukraine.

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Kuchmerovska, T., Tykhonenko, T., Yanitska, L. et al. Nicotinamide and Nicotinoyl-Gamma-Aminobutyric Acid as Neuroprotective Agents Against Type 1 Diabetes-Induced Nervous System Impairments in Rats. Neurochem Res 50, 1 (2025). https://doi.org/10.1007/s11064-024-04257-y

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