Naslov
From determining brain insulin resistance in a sporadic Alzheimer’s disease model to exploring the region-dependent effect of intranasal insulin

Autori
Knezović, Ana ; Budiša, Stjepan ; Babi Perhoč, Ana ; Homolak, Jan ; Osmanović Barilar, Jelena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
MNS 2022: The proceedings, Xjenza 10 Special Issue / - , 2022, 134-135

Skup
8th Mediterranean Neuroscience Society Conference (MNS)

Mjesto i datum
Dubrovnik, Hrvatska, 29.05.2022. - 02.06.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
insulin resistance ; streptozotocin ; intranasal insulin

Sažetak
Impaired response to insulin has been linked to many neurodegenerative disorders like Alzheimer’s disease (AD). In line with this finding, an animal model of sporadic AD has been developed by intracerebroventricular (icv) administration of streptozotocin (STZ), which given peripherally causes insulin resistance. Brain insulin resistance is defined in literature as poor signaling of insulin receptors, reduced insulin levels in the brain and/or reduced trafficking of insulin into the brain and other, so far unknown processes. Can we really consider the level of insulin in the brain as an indicator of insulin resistance and can we acknowledge insulin resistance based solely on changed protein levels and activity of the insulin receptor signaling cascade? To explore the possible presence of brain insulin resistance in the STZ-icv model, we measured neuronal activity (c-fos levels) after intranasal insulin administration that enables the delivery of insulin to the brain with the relative absence of systemic uptake and related peripheral side effects. On account of the unexplored diverse insulin role in the brain and mechanism of its beneficial effect on cognition, we wanted to explore the effect of acute IN insulin administration on peripheral metabolic and central glutamatergic and metabolic parameters in cognitively normal rats in comparison to rats with cognitive deficit (STZ-icv rat model of sAD). STZ and insulin brain region-specifically altered the levels and activity of proteins involved in cell metabolism and glutamate signaling. Insulin did not produce a systemic response, while central changes found after IN insulin in STZ-icv rats suggest insulin sensitivity of hippocampal and cortical regions (temporal). Altered metabolic parameters in hypothalamus of STZ-icv rats were not normalized by IN insulin, indicating possible insulin insensitivity. Brain insulin sensitivity depends on the affected brain region and presence of metabolic dysfunction.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA