Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats

The diabetic brain and cognition

“…These data support possible causal role of IRBS in sAD etiopathogenesis de la Monte et al 2014), confirmed by therapeutic effect of icv insulin in this model (Shingo et al 2013) and intranasal insulin in AD patients (Claxton et al 2015), and contributing role of vascular pathology in progression of cognitive decline as demonstrated in 9-month follow-up studies of this model Salkovic-Petrisic et al 2011).…”

“…Many studies suggest that adding more insulin to the brain would improve memory and prevent cell damage (Shingo et al 2013;Claxton et al 2015). In individuals without DM, it has been shown amongst cognitively intact and cognitively impaired individuals that a form of insulin that enters the brain selectively has beneficial effects on some cognitive domains (Shemesh et al 2012).…”

“…Long-term drug testing polygon considering the preliminary data of the therapeutic role of icv insulin in the STZ-icv model (Shingo et al 2013) and of intranasal insulin in AD patients (Claxton et al 2015) should be performed to elucidate the importance of glucose/insulin pathology as risk factor for both, AD and VaD.…”

Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease

“…Animal model which develops insulin resistant brain state and glucose hypometabolism following the intracerebroventricular application of a betacytotoxic drug streptozotocin in small rodents and cynomolgus monkey (STZ-icv model), (Agrawal et al 2011;Grünblatt et al 2007;Lannert and Hoyer 1998;Lee et al 2014;Lester-Coll et al 2006;Plaschke and Hoyer 1993;Salkovic-Petrisic et al 2006), shares similarities with the human sAD condition (Lannert and Hoyer 1998) since insulin resistant brain state was found postmortem in sAD patients (Correia et al 2011;de la Monte and Wands 2005;Frölich et al 1998). Additionally, STZ-icv model demonstrates also cognitive deficits (Mayer et al 1990;Lannert and Hoyer 1998) and decrement in cerebral cholinergic transmission (Blokland and Jolles 1993;Hellweg et al 1992), as well as other features of chronic neurodegeneration like oxidative stress and neuroinflammation (Saxena et al 2011;Sharma and Gupta 2001) and in particular tau protein hyperphosphorylation (Grünblatt et al 2007;Deng et al 2009;Liu et al 2014;Peng et al 2013), pathological Aβ accumulation (Shingo et al 2013) and cerebral amyloid angiopathy (Salkovic-Petrisic et al 2006, 2011.…”

Adipobiology of the brain: From brain diabetes to adipose Alzheimer‘s disease

“…In brief, an extraneuronal production of both APP and Aβ peptides including the adipose tissue was demonstrated (25)(26)(27)(28)(29)(30). Accordingly, the administration of streptozotocin (STZ), a well known experimental model for diabetes, induces brain insulin resistance and cognitive alterations resembling those in AD patients (31)(32)(33). We have reported that STZ-induced diabetes is associated with changes in NGF levels in both pancreas and brain (34).…”