Streptozocin-induced Alzheimer's disease as an independent risk factor for the development of hyperglycemia in Wistar rats

  • Authors: Stavrovskaya A.1, Voronkov D.2, Shestakova E.3, Gushchina A.4, Ol'shanskiy A.4, Yamshikova N.5
  • Affiliations:
    1. Federal State Budget Scientific Institution Research Center of Neurology, Moscow, Russian Federation
    2. ФГБНУ "Научный центр неврологии"
    3. ФГБУ «НМИЦ эндокринологии» Минздрава России, Москва, Россия
    4. ФГБНУ Научный центр неврологии
    5. ФГБНУ научной центр неврологии
  • URL: https://probl-endojournals.ru/probl/article/view/12126
  • DOI: https://doi.org/10.14341/probl12126
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Abstract


Background: The relationship of Alzheimer's disease (AD) and metabolic disorders is widely discussed. Nevertheless, it remains unclear whether AD is a direct cause of carbohydrate metabolism disorders or it is the presence of classical risk factors for type 2 diabetes mellitus (DM 2), primarily obesity, that significantly increases the risk of AD.

Aim: To evaluate the separate contribution of two factors to the development of disorders of carbohydrate metabolism: (1) weight gain due to a high-calorie diet and (2) experimental-induced AD.

Materials and methods: Male Wistar rats were injected with streptozocin (STZ) in the lateral ventricles of the brain to induce AD or saline (sham operated animals - SO) during stereotactic operations. After 2 weeks, the animals were divided into four groups: 1) the SO group with the normal calorie (NCD) diet (SO NCD); 2) the SO group with the high-calorie diet (SO HCD); 3) the group with the NCD which was prescribed after the administration of STZ (STZ NCD); 4) the group to which the HCD was assigned after the administration of STZ (STZ HCD). Intraperitoneal glucose tolerance tests were carried out before the diet and after 3 months of diet. Then morphological assessments of brain tissue, pancreas, and liver were performed.

Results: After 3 months, the glycemic curves significantly differed in the 4 studied groups: normoglycemia persisted only in the SO + NCD group, while HCD and the STZ administration were accompanied by the development of hyperglycemia (p = 0.0001). The STZ + NСD group, which represented the isolated effect of AD, was also characterized by impaired carbohydrate metabolism. A morphological study showed that HCD leads to a more pronounced ectopic accumulation of fat in the liver and pancreas tissue than NCD. The administration of STZ, regardless of the diet, led to changes typical for the AD model - an increase in the size of the ventricles of the brain, degeneration of white matter, and the accumulation of β-amyloid in the hypothalamus.

Conclusions: The STZ-induced hypothalamus damage typical for AD led to impaired carbohydrate metabolism regardless of diet and was an independent risk factor for hyperglycemia.


Alla Stavrovskaya

Federal State Budget Scientific Institution Research Center of Neurology, Moscow, Russian Federation

Author for correspondence.
Email: alla_stav@mail.ru
ORCID iD: 0000-0002-8689-0934
SPIN-code: 8013-7362
Scopus Author ID: 8322296500
ResearcherId: C-7098-2012

Russian Federation, RESEARCH CENTER OF NEUROLOGY, MOSCOW, RUSSIA 125367, Moscow, Volokolamskoe av., 80

кандидат биологических наук, заведующий лабораторией экспериментальной патологии нервной системы

Dmitriy Voronkov

ФГБНУ "Научный центр неврологии"

Email: voronkov@neurology.ru
ORCID iD: 0000-0001-5222-5322
SPIN-code: 1576-8871
Scopus Author ID: 23010332800
ResearcherId: B-3910-2012

Russian Federation, RESEARCH CENTER OF NEUROLOGY, MOSCOW, RUSSIA

PhD, senior researcher

Ekaterina Shestakova

ФГБУ «НМИЦ эндокринологии» Минздрава России, Москва, Россия

Email: katiashestakova@mail.ru
ORCID iD: 0000-0001-6612-6851
SPIN-code: 1124-7600

Russian Federation, Москва, 117036, ул. Дмитрия Ульянова, 11

MD, PhD, leading research associate

Anastasiya Gushchina

ФГБНУ Научный центр неврологии

Email: anastaisha-2015@mail.ru
ORCID iD: 0000-0003-3026-0279
SPIN-code: 4017-5024
Scopus Author ID: 57200116939

Russian Federation, RESEARCH CENTER OF NEUROLOGY, MOSCOW, RUSSIA

научный сотрудник лаборатории экспериментальной патологии нервной системы

Artyom Ol'shanskiy

ФГБНУ Научный центр неврологии

Email: AS0769@yandex.ru
ORCID iD: 0000-0002-5696-8032
SPIN-code: 7072-0721

Russian Federation, RESEARCH CENTER OF NEUROLOGY, MOSCOW, RUSSIA

кандидат биологических наук, старший научный сотрудник лаборатории экспериментальной патологии нервной системы

Nina Yamshikova

ФГБНУ научной центр неврологии

Email: nyamshikova@yandex.ru
ORCID iD: 0000-0003-4387-2266
SPIN-code: 9385-5576
Scopus Author ID: 6503897870

Russian Federation, RESEARCH CENTER OF NEUROLOGY, MOSCOW, RUSSIA

PhD, leading researcher

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