Effect of intraperitoneal or intracerebroventricular injection of streptozotocin on learning and memory in mice

Abstract

Alteration of behavior and PSD proteins in cerebral cortex and hippocampal synaptosome in the Alzheimer's disease (AD) mouse model were determined. AD was established by intraperitoneal injection of streptozotocin (STZ) in neonatal mice (intraperitoneal AD group) or intracerebroventricular injection of STZ in adult mice (intracerebroventricular AD group). Body weight and blood sugar level were measured. Following Morris water maze (MWM) test and fear-conditioning test, cerebral cortex and hippocampus tissues were collected and the levels of PSD95 and shank3 proteins in these tissues were measured by western blot analysis. The body weight was reduced and the blood sugar concentration was increased in the intraperitoneal AD group compared with the control group. In contrast, the body weight was reduced, while the blood sugar concentration was not increased in the intracerebroventricular AD group compared with the control group. Escape latency in both AD groups was extended compared with the control group. The freezing time in the intraperitoneal AD group was increased, while in the intracerebroventricular AD group, the freezing time was reduced. PSD95 and shank3 proteins in the cerebral cortex in both AD groups were decreased compared with the control group. PSD95 in the hippocampus was reduced in both AD groups compared with the control group. Shank3 in the hippocampus in the intracerebroventricular AD group was significantly reduced compared with the control group. Intraperitoneal injection of STZ in neonatal mice led to elevated blood sugar, impaired spatial memory and enhanced emotional memory when they become adults. In contrast, intracerebroventricular injection of STZ in adults directly led to deteriorated spatial and emotional memory without alteration of blood sugar content, which could be associated with the changes of PSD95 and shank3 proteins in hippocampus.

Synaptic loss and amyloid beta alterations in the rodent hippocampus induced by streptozotocin injection into the cisterna magna

“…Loss of body weight is a common characteristic in AD patients and ICV-STZ rodents have also been shown to lose weight without experiencing any change in blood glucose [11]. In our study, CM-STZ caused weight loss during the injection period, which recovered to control An additional benefit of CM-STZ injection model is the ability to administer many injections over time, due to the reduced invasiveness of the procedure.…”

Key role of MIF-related neuroinflammation in neurodegeneration and cognitive impairment in Alzheimer’s disease

“…ICV-STZ has been shown to induce contextual memory deficits in mice (Zhang et al 2018). To assess the involvement of MIF in contextual memory deficits, we tested the behavior of the different experimental groups using the fear conditioning paradigm.…”

“…The ICV-STZ mouse model is a non-transgenic mouse model mimicking some aspects of sporadic AD, including neuroinflammation, disruption of tau phosphorylation, insulin signaling, Aβ pathology and cognitive deficits (Nazem et al 2015;Grunblatt et al 2007;Salkovic-Petrisic et al 2006;Chen et al 2012;Grieb 2016;Zhang et al 2018).…”

Advance of sporadic Alzheimer's disease animal models

“…STZ (intraperitoneal or intracerebroventricular injection) might cause insulin deficiency, as well as Aβ deposition, hyperphosphorylation of Tau protein, loss of neurons, and other AD pathologies in brain . Reeta et al injected STZ (3 mg·kg −1 ) into rats’ ventricle and found that the oxidative stress, acetylcholinesterase activity, and inflammatory cytokines have been increased both in hippocampus and cortex in rats.…”

“…STZ (intraperitoneal or intracerebroventricular injection) might cause insulin deficiency, as well as Aβ deposition, hyperphosphorylation of Tau protein, loss of neurons, and other AD pathologies in brain. [49][50][51][52][53][54][55] Reeta Amyloid-related 21 0 5 21 57 Cholesterol 2 0 1 0 3 Cholinergic system 3 4 5 18 30 Inflammation 14 0 3 8 25 Other neurotransmitters 16 1 1 19 37 Tau 11 0 1 4 16 Unknown 10 0 3 4 17 Other 39 0 6 13 58 et al injected STZ (3 mg·kg −1 ) into rats' ventricle and found that the oxidative stress, acetylcholinesterase activity, and inflammatory cytokines have been increased both in hippocampus and cortex in rats. As a result, cognitive defects were also observed on the 28th day post STZ injection.…”